--- title: Disease Atlas Methodology description: "The methodology behind Euretos Disease Atlas: causal target ranking at cell-type resolution across 34,000 diseases, calibrated and traceable to source." --- [![Euretos Logo](https://www.euretos.com/hubfs/Euretos%20Logo%202020%20-%20Strapline%20-%20White%20small.png)](https://www.euretos.com?hsLang=en) [Disease Atlas](https://www.euretos.com/disease-atlas?hsLang=en) [Get Access](https://www.euretos.com/pricing?hsLang=en) [Blog](https://www.euretos.com/blog?hsLang=en) [![Login](https://hubspot-no-cache-eu1-prod.s3.amazonaws.com/cta/default/7609166/interactive-167498164057.png)](https://cta-eu1.hubspot.com/web-interactives/public/v1/track/redirect?encryptedPayload=AVxigLJf9pG9laoInA%2Bz8gKxkaZMXkYxVyrWH1l5uNHVK%2Fo5oOtg%2B143DZtLL6U8nfdppuWGIHX22fcdi2LKOcCWNpHF7l4L1Cy6ljyre9W1LuhvqK7Le4IObRfcDMu1ZeUcGj9AS2K2VBbUvXF7LJcfZDfdIINbh9uVaq1L56f4cZiLgGpS4XVfBg%3D%3D&webInteractiveContentId=167498164057&portalId=7609166) [![Contact Us](https://hubspot-no-cache-eu1-prod.s3.amazonaws.com/cta/default/7609166/interactive-167498163994.png)](https://cta-eu1.hubspot.com/web-interactives/public/v1/track/redirect?encryptedPayload=AVxigLJf9pG9laoInA%2Bz8gKxkaZMXkYxVyrWH1l5uNHVK%2Fo5oOtg%2B143DZtLL6U8nfdppuWGIHX22fcdi2LKOcCWNpHF7l4L1Cy6ljyre9W1LuhvqK7Le4IObRfcDMu1ZeUcGj9AS2K2VBbUvXF7LJcfZDfdIINbh9uVaq1L56f4cZiLgGpS4XVfBg%3D%3D&webInteractiveContentId=167498163994&portalId=7609166) **Target assessment** · Disease Atlas by Euretos # Example assessment: GABRB1 in Alzheimer's disease. A complete gene-disease assessment from the Disease Atlas, shown as generated. Fifteen panels cover genetic evidence, developability, safety, competition, score decomposition, expression, mechanism, networks, phenotypes, literature, clinical trials, structure, perturbation and cell lines. Panels [1 · Genetic Evidence](https://www.euretos.com/genedisease-example#genetic-evidence)[2 · Developability](https://www.euretos.com/genedisease-example#developability)[3 · Safety](https://www.euretos.com/genedisease-example#safety)[4 · Competition](https://www.euretos.com/genedisease-example#competition)[5 · Evidence Sources & Score Decomposition](https://www.euretos.com/genedisease-example#score-decomposition)[6 · Transcriptomics](https://www.euretos.com/genedisease-example#transcriptomics)[7 · Differential Expression](https://www.euretos.com/genedisease-example#differential-expression)[8 · Mechanistic Chain](https://www.euretos.com/genedisease-example#mechanistic-chain)[9 · Protein Networks](https://www.euretos.com/genedisease-example#protein-networks)[10 · Phenotypes](https://www.euretos.com/genedisease-example#phenotypes)[11 · Literature](https://www.euretos.com/genedisease-example#literature)[12 · Clinical Trials](https://www.euretos.com/genedisease-example#clinical-trials)[13 · Protein Structure](https://www.euretos.com/genedisease-example#protein-structure)[14 · Perturbation](https://www.euretos.com/genedisease-example#perturbation)[15 · Cell Lines](https://www.euretos.com/genedisease-example#cell-lines) Role of GABRB1 (homo sapiens) in alzheimer's disease ENSG00000163288P18505HGNC:4081 TIER 1Full ranked evidence — biology, translational, tractability, safety, claims engine narrative.Disease tier ATPS snapshot 2026-06-11Live Biology 100 Translational 100 Tractability 72 Safety 8 Priority 80 Confidence A Biology drivers:Genetic0.04Network0.03Expression0.06Transfer0.32 Biology Strong causal evidence. Strongest support from cross-disease transfer. Translational High development plausibility. Key factors: approved drug target in another indication. Safety High predicted cardiac toxicity risk (0.84) High sequence similarity with paralogs Highly competitive target space (38 drugs) Elevated cns risk (disease-relevant organ). Tractability Best modality: small molecule. 58 approved drug(s) targeting this gene. Highly crowded (38 drugs: 2 approved, 10 in clinical trials) - differentiation critical - validated target High developability risk (HIGH). Target validated with 2 approved drug(s) Recommended posture Deprioritize Shared recommendation — synthesis of all 14 evidence axes ℹHigh predicted cardiac toxicity risk (0.84) | High sequence similarity with paralogs | Highly competitive target space (38 drugs) Branchnon\_cancerModalitysmall molecule CompetitionVERY HIGH ValidationAPPROVED Opportunity noteHighly crowded (38 drugs: 2 approved, 10 in clinical trials… Evidencehigh ### Key findings - **Strong translational precedent** **GABRB1** has strong development precedent — 2 approved drug(s) and 10 in clinical development across all indications (APPROVED, competition: VERY\_HIGH). The target has been demonstrably drugged; the question for **alzheimer's disease** is indication fit and differentiation, not feasibility. C-PRC-01.strong · 2 counterarguments - **Saturated competitive landscape** **GABRB1** sits in a saturated field — 38 drugs (any indication), 2 approved, 10 in clinical (VERY\_HIGH competition). The target is mature: entry requires a strong differentiation thesis (novel modality, underserved indication, biomarker-stratified subpopulation, combination strategy). Saturated is not a no-go — but the commercial bar is high. C-CMP-01.saturated · No counters or absences recorded. - **Weak causal genetic support** **GABRB1** has weak causal genetic signal for **alzheimer's disease** (composite score 100.0). Genetic axis 0.04; the score is mostly carried by network (0.03), expression (0.06), and/or transfer-learning (0.32) axes rather than direct genetic evidence. C-GEN-01.weak · 5 counterarguments · 1 absence - **Dispersed mechanism** A graph-connected path from **GABRB1** to **alzheimer's disease** exists (4 of 4 middle layers populated) but no single theme dominates — 11 themes are hit across the full scoring population — this can be a larger set than the topK nodes trimmed onto this chart, so this count and the diagram may not match — none above the convergence threshold. Path existence alone does not establish a validated mechanism — some populated layers may route through tissue-, development-, or pathway-remote nodes; deriving a coherent, disease-relevant therapeutic hypothesis from this chain is difficult without further triage. C-MEC-01.weak · 1 counterargumentTheme count reflects the currently selected cell type in Panel 8. ### 1Genetic Evidence DEFAULT Biology score 100.0 Genetic driver 4.0% Confidence Disease tier (ranking source) A · Evidence confidence: high Mendelian Randomisation — tissue eQTL evidence Heart\_Left\_Ventricle: Steiger-correct — the gene-to-disease causal direction holds for this instrument.n=10, F=44Heart\_Left\_VentricleArtery\_Tibial: Steiger-correct — the gene-to-disease causal direction holds for this instrument.n=10, F=22Artery\_TibialColon\_Sigmoid: Steiger-correct — the gene-to-disease causal direction holds for this instrument.n=10, F=17Colon\_SigmoidArtery\_Coronary: Steiger-correct — the gene-to-disease causal direction holds for this instrument.n=10, F=27Artery\_CoronaryHeart\_Atrial\_Appendage: Steiger-correct — the gene-to-disease causal direction holds for this instrument.n=10, F=26Heart\_Atrial\_Appendage0.000.020.040.06β (standardised effect size) Steiger-correct Reverse causation candidate ·Colour is per-row (hover a row for its own Steiger result) · sorted by rank · point size ∝ log₁₀(N SNPs) · bars = 95 % CI ▸Variant evidence · click to expand Weak causal genetic support **GABRB1** has weak causal genetic signal for **alzheimer's disease** (composite score 100.0). Genetic axis 0.04; the score is mostly carried by network (0.03), expression (0.06), and/or transfer-learning (0.32) axes rather than direct genetic evidence. C-GEN-01.weak · 3 evidence refs · 5 counterarguments · 1 absence composite score1.00 genetic axis0.04 network axis0.03 Score driven by non-genetic axes The composite score is supported primarily by network (0.03), expression (0.06), and/or transfer-learning (0.32) signals rather than direct genetic evidence (genetic axis only 0.04). Interpret the causal claim with caution — the score may reflect proximity in regulatory or expression space rather than a Mendelian-randomized causal effect. low\_genetic\_signal · moderate Warning flag noted An overlay warning is associated with this pair: *High predicted cardiac toxicity risk (0.84) | High sequence similarity with paralogs | Highly competitive target space (38 drugs)*. Read alongside the safety panel before acting on the causal claim. warning\_flag · minor Genetic signal rests on a single study Only 1 GWAS study contributes variants for **GABRB1** × **alzheimer's disease**; the best-supported single variant appears in 1 study/studies. An unreplicated association carries an inflated effect size more often than not — treat the locus as provisional until an independent cohort reports it. single\_study\_only · moderate Common variants only, none coding-impactful All 1 recorded variants for **GABRB1** are common (gnomAD allele frequency ≥ 5%) and none carries a HIGH putative impact. Common non-coding associations usually tag a regulatory haplotype rather than pinpoint a causal allele, and their per-allele effects are small, so the direction they imply for a therapeutic is correspondingly weaker. common\_variant\_only · moderate All variants are regulatory Every one of the 1 variants recorded for **GABRB1** falls in a regulatory consequence class — none alters the coding sequence. That is consistent with a change in expression rather than in protein function, so read this locus alongside the expression and perturbation panels before inferring a mechanism. regulatory\_only · moderate **No Mendelian randomization available.** Mendelian randomization was not computed for this pair. Either no eligible eQTL instruments exist for the gene in disease-relevant tissue, or no GWAS is available in the registry for the disease. The genetic axis falls back to other evidence (LoF burden, network propagation) where available. no\_mr\_direction · reduces\_strength ### 2Developability DEFAULT Overall tractability Score 4.0 Best modalitySmall moleculeDevelopability riskHIGH (0.80) Modality tractability scores 0–10 scale · ≥4 HIGH (green) · 1–4 MEDIUM (amber) · \<1 LOW (grey) Rows marked ÷10 were reported on the scorecard's 0–100 modality scale and are shown rescaled, with the scorecard's own rating — its band cut-points differ from the thresholds above. Small molecule 4.0 HIGH · 58 approved drug(s), any indication · details Known ligandsYes ChEMBL ligands19 Best pChEMBL6.89 Approved drugsFLUMAZENIL, DIAZEPAM, PENTOBARBITAL, METHARBITAL, CHLORDIAZEPOXIDE Antibody / mAb 3.5 MEDIUM · 0 approved drug(s), any indication · details mAb confidence1 ADC 7.7÷10 TCE 8.0÷10 Bispecific 8.3÷10 Dual TCE 7.3÷10 Target classification Best modalitySmall moleculeMembraneYesExtracellular domainYesSecretedNoExtracellular fraction0.46SelectivityHIGH riskParalogs18 Chemistry Known ligandsYes ChEMBL ligands19 Best pChEMBL6.89 Approved drugs (all modalities)58 SINK-EFFECT RISK (PK / modality fit) LOW Immune TPM0.00 Hematopoietic load0.02 Moderate tractability **GABRB1** is moderately tractable. Overall score 4.0 (HIGH); best modality **small molecule**. Pharmacology starting points: 19 ChEMBL ligand(s), maximum pChEMBL 6.9. Approved precedent: 58 drug(s) (any indication). Developability risk: HIGH. C-TRC-01.moderate · 5 evidence refs · 2 counterarguments tractability overallHIGH0.50 best modalitysmall\_molecule1.00 approved drugs58 approved1.00 ligand pharmacologypChEMBL 6.8950.77 antibody accessible surface1.00 High developability risk Developability risk is rated **HIGH** (primary risk: selectivity). Even with strong tractability, manufacturing, stability, or immunogenicity hurdles may block development. Review the developability assessment before advancing. high\_developability\_risk · blocking High paralog similarity — off-target selectivity hurdle 18 sequence-similar paralog(s) exist, with closest at 77.1% identity. Off-target binding to family members is a likely failure mode; selectivity assays against the paralog panel are critical. Examples of this pattern: GPCR class B/secretin family, kinase paralog families, nuclear-receptor families. high\_paralog\_similarity · blocking ### 3Safety DEFAULT 6 × 4 organ risk matrix Rows: organs · Columns: evidence tiers | | Predicted | FAERS-bridged | AE-grounded | Clinical | | --- | --- | --- | --- | --- | | Liver | MEDIUM 52 drug(s) | — | — | — | | Heart | HIGH 52 drug(s) | — | — | — | | Kidney | HIGH 52 drug(s) | — | — | — | | Lung | MEDIUM 52 drug(s) | — | — | — | | CNS | HIGH 52 drug(s) | — | — | — | | Immune | HIGH 52 drug(s) | — | — | — | Overall riskHIGH · 0.99τ-tissue0.97τ-cell0.92 Drugs bridged52 pLI0.73LOEUF0.56 Significant safety concerns (FAERS-concordant) **GABRB1** has significant safety concerns. Overall risk rating **HIGH** (0.99); 4 organ(s) flagged HIGH risk (primary: multiple organs — predictions saturated, see counterarguments below). Evidence class: model-predicted, concordant with FAERS post-market adverse-event reporting across 52 bridged drug(s). Tissue expression tau = 0.97, breadth 1. Carefully review the counterarguments — note that high prediction scores may be saturated for clinically-validated targets (Phase-2 calibration caveat), and this rating does not carry a documented calibration/performance metric or threshold provenance. C-SAF-01.weak · 3 evidence refs · 1 counterargument overall safety scoreHIGH0.01 tissue specificity0.97 constraint scoreconstrained0.73 Saturated organ risk predictions 4 of 6 organs predicted as HIGH risk with \`primary\_concern\_flag = 'uniform'\` — the model could not differentiate which organ is dominant. This is the canonical Phase-1-patch indicator that organ risk predictions are saturated for clinically-validated targets (the EGFR pattern: real AE data underlies the predictions but specificity is lost above ~0.95). Treat individual organ rankings as low-resolution; the overall risk magnitude is informative, the per-organ attribution is not. saturated\_predictions · moderate ### 4Competition DEFAULT Competition landscape — same target / adjacent (PPI 1-hop) / pathway match Programs recorded in the selected indication only · Stacked by program outcome: approved (green) · clinical (amber) · failed (red) Source: AACT trial registry × drug-target mappings × PPI/pathway adjacency, snapshot 2026-06-10 · counts are deduplicated programs (drug + target gene), not raw NCT rows — a multi-trial drug counts once, by outcome precedence approved \> any non-discontinued clinical \> all-discontinued failed. "Direct" = same target gene; "adjacent" = PPI 1-hop or Reactome pathway co-member. GABRB1 (same target) 0a / 3c / 0f GABRA1 (PPI 1-hop) 0a / 3c / 0f GABRG2 (PPI 1-hop) 0a / 3c / 0f GABRA2 (PPI 1-hop) 0a / 2c / 0f GABRA3 (PPI 1-hop) 0a / 2c / 0f GABRA4 (PPI 1-hop) 0a / 2c / 0f Approved Clinical Failed By modality Other 33 By sponsor Mayo Clinic 15 Pfizer 15 Brasilia University Hospital 3 Direct0 / 3 / 0 Adjacent (PPI 1-hop)0 / 28 / 0 Pathway / family0 / 2 / 0 Strong translational precedent **GABRB1** has strong development precedent — 2 approved drug(s) and 10 in clinical development across all indications (APPROVED, competition: VERY\_HIGH). The target has been demonstrably drugged; the question for **alzheimer's disease** is indication fit and differentiation, not feasibility. C-PRC-01.strong · 4 evidence refs · 2 counterarguments approved drug count2 approved0.40 clinical pipeline10 in clinical1.00 validation levelAPPROVED competition levelVERY\_HIGH Selectivity risk — close paralogs The closest paralog shares 77.1% sequence identity (18 paralog(s) total). Achieving clean selectivity will be hard; off-target activity against the paralog(s) may drive both efficacy and toxicity outcomes. Note: selectivity is a tractability constraint, not a veto — many successfully-drugged targets (kinases, GPCRs) live in dense paralog families. paralog\_selectivity\_risk · moderate Paralog compensation risk This gene has 18 paralogs with a redundancy index of 68.9. Inhibition of the target may be compensated by paralog upregulation, eroding sustained efficacy. Consider whether the therapeutic strategy requires multi-paralog targeting or a different mechanism (degradation, downstream pathway intervention). paralog\_redundancy\_risk · moderate Cross-indication target precedent (all diseases). Saturated competitive landscape **GABRB1** sits in a saturated field — 38 drugs (any indication), 2 approved, 10 in clinical (VERY\_HIGH competition). The target is mature: entry requires a strong differentiation thesis (novel modality, underserved indication, biomarker-stratified subpopulation, combination strategy). Saturated is not a no-go — but the commercial bar is high. C-CMP-01.saturated · 6 evidence refs competition levelVERY\_HIGH drug count38 drugs (2 approved, 10 in clinical, 0 failed)1.00 validation levelAPPROVED opportunity assessmentHighly crowded (38 drugs: 2 approved, 10 in clinical trials) - differentiation critical - validated target direct clinical precedent4 direct program(s), max phase phase\_3 (0 active, 48 completed, 0 discontinued)0.20 adjacent clinical precedent44 adjacent program(s) (PPI 1-hop or pathway co-member), max phase phase\_3 (adjacent-mechanism evidence, not direct target validation)0.88 Landscape band and drug counts are target-wide (any indication); the direct/adjacent program evidence below is specific to the selected indication. ### 5Evidence Sources & Score Decomposition DEFAULT 5-axis score radar Biology · Translational · Tractability · Safety · Priority — 0–100 Biology: 100.0 — Strong causal evidence. Strongest support from cross-disease transfer.Translational: 99.9 — High development plausibility. Key factors: approved drug target in another indication.Tractability: 72.0 — Best modality: small\_molecule. 58 approved drug(s) targeting this gene. Highly crowded (38 drugs: 2 approved, 10 in clinical trials) - differentiation critical - validated target High developability risk (HIGH). Target validated with 2 approved drug(s)Safety: 8.2 — High predicted cardiac toxicity risk (0.84) High sequence similarity with paralogs Highly competitive target space (38 drugs) Elevated cns risk (disease-relevant organ).Priority: 79.8Biology100Translational100Tractability72Safety8Priority80 Evidence confidence: **high** · Disease tier (ranking source) A Biology drivers:Genetic0.04Network0.03Expression0.06Transfer0.32 Deprioritize **GABRB1** for **alzheimer's disease** should be deprioritized: causal biology is weak: C-GEN-01 landed at weak or absent, leaving nothing to build a case on. Re-entry is conditional on the underlying signal changing (new safety data, new tractability assessment, new genetic instruments). C-CMR-01.deprioritize · 14 evidence refs · 2 counterarguments causal biology bandC-GEN-01: weak tractability bandC-TRC-01: moderate safety bandC-SAF-01: weak precedent bandC-PRC-01: strong mechanism bandC-MEC-01: weak landscape bandC-CMP-01: saturated cell type context bandC-CTX-01: partial network proximity bandC-NET-01: isolated de concordance bandC-DE-01: detected\_unsourced perturbation bandC-PRT-01: absent phenotype overlap bandC-PHE-01: absent literature bandC-LIT-01: absent structural developability bandC-STR-01: small\_molecule\_favourable cell line strategy bandC-BIO-01: no\_dependency Thin biology evidence Both causal genetic evidence (C-GEN-01) and mechanism coherence (C-MEC-01) are weak or absent. Neither alone would be disqualifying, but the conjunction signals the gene-disease link is not well-supported on either the evidence axis or the mechanism axis. A pursue verdict would lean on translational precedent or competition signals that may not transfer. biology\_thin · moderate Multiple non-blocking concerns 4 of the upstream claims land at weak/absent. No single dimension blocks the pursuit, but the cumulative weight is meaningful — the verdict has fewer defensible legs to stand on. Read the individual upstream claims to understand which dimensions are softest. multiple\_concerns · moderate ### 6Transcriptomics DEFAULT Disease CTs GTEx tissues HPA cell types scRNA expression heatmap — disease cell types Top-5 disease-relevant cell types · CCIS v2 disease-relevant cell types (flat rank, no section membership) · Median expression · not tissue/compartment-gated 2 of 5 row(s) have a measured value for GABRB1 · a dash (—) means no measurement was recorded, not a measured zero | | GABRB1 | CD3D | CD3G | TNFSF13B | IFNL4 | IRAK2 | PTPN13 | SIGLEC16 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | glutamatergic neuron | — | — | — | — | — | — | — | — | | astrocytes | 1.1 | — | 0.0 | 0.9 | — | 3.5 | 13.2 | 0.1 | | gabaergic neurons | — | — | — | — | — | — | — | — | | central nervous system neuron | 4.7 | 0.3 | 0.1 | 1.0 | 0.0 | 1.3 | 3.7 | 0.2 | | interneurons | — | — | — | — | — | — | — | — | Partial cell-type alignment **GABRB1** has partial cell-type support for **alzheimer's disease**: a CCIS pathway × cell-type bridge connects the gene to 7 disease-relevant cell type(s) — model-derived signal, not a claim about the displayed expression matrix — but the case is not fully landed. Specificity is τ-cell 0.92. The cell-type axis is consistent with the mechanism but not the headline driver; the other axes (genetic, network) carry more of the case. C-CTX-01.partial · 4 evidence refs expression expert signalp\_expression = 0.0650.06 expression specificityτ-cell 0.92, τ-tissue 0.970.92 ccis pathway celltype bridge7 CCIS pathway×cell-type overlap(s)0.70 disease celltype context5 disease cell type(s) annotated ### 7Differential Expression DEFAULT DE volcano — alzheimer's disease vs reference expression GABRB1 + 200 most disease-relevant genes · Disease Atlas gene-regulation aggregate 0.01.02.13.14.10491318log2 fold-change−log10(adj. p)GABRB1 — up, log2FC 2.75, p 5.1e-4, adj. p 2.4e-3GABRB1CTXN1 — up, log2FC 3.87, p 0, adj. p 0CTXN1RTN2 — up, log2FC 3.83, p 0, adj. p 0RTN2LINC01003 — up, log2FC 3.76, p 0, adj. p 0LINC01003MTSS2 — up, log2FC 3.69, p 0, adj. p 0RABGAP1L-AS1 — up, log2FC 3.58, p 0, adj. p 0RIN1 — up, log2FC 3.37, p 0, adj. p 0ELAPOR2 — up, log2FC 3.33, p 0, adj. p 0GSTT2B — up, log2FC 3.30, p 0, adj. p 0C2CD6 — up, log2FC 3.18, p 0, adj. p 0RPL34-DT — up, log2FC 3.18, p 0, adj. p 0LINC02207 — up, log2FC 3.04, p 0, adj. p 0PAQR9 — up, log2FC 3.00, p 0, adj. p 0MIRLET7A1HG — up, log2FC 3.00, p 0, adj. p 0SAMD12-AS1 — up, log2FC 2.89, p 0, adj. p 0RHEBL1 — up, log2FC 2.89, p 0, adj. p 0MFF-DT — up, log2FC 2.89, p 0, adj. p 0SOWAHC — up, log2FC 2.83, p 0, adj. p 0MESP1 — up, log2FC 2.83, p 0, adj. p 0HEY1 — up, log2FC 2.83, p 0, adj. p 0LINC02281 — up, log2FC 2.83, p 0, adj. p 0NAA11 — up, log2FC 2.77, p 0, adj. p 0G2E3-AS1 — up, log2FC 2.71, p 0, adj. p 0C8ORF44 — up, log2FC 2.64, p 0, adj. p 0LINC02607 — up, log2FC 2.64, p 0, adj. p 0LINC02343 — up, log2FC 2.64, p 0, adj. p 0SOX2 — up, log2FC 2.56, p 0, adj. p 0BEGAIN — up, log2FC 2.56, p 0, adj. p 0LINC01106 — up, log2FC 2.56, p 0, adj. p 0SHB — up, log2FC 2.56, p 0, adj. p 0FUT1 — up, log2FC 2.48, p 0, adj. p 0KCNK3 — up, log2FC 2.48, p 0, adj. p 0cytochrome p450, family 4, subfamily f, polypeptide 26, pseudogene — up, log2FC 2.48, p 0, adj. p 0PPP1R3G — up, log2FC 2.48, p 0, adj. p 0BCL6B — up, log2FC 2.48, p 0ZNF687-AS1 — up, log2FC 2.48, p 0, adj. p 0MGC4859 — up, log2FC 2.48, p 0, adj. p 0NTSR1 — up, log2FC 2.40, p 0, adj. p 0TMEM114 — up, log2FC 2.40, p 0, adj. p 0RAB19 — up, log2FC 2.40, p 0, adj. p 0ASAP1-IT2 — up, log2FC 2.40, p 0, adj. p 0SHANK1 — up, log2FC 2.40, p 0, adj. p 0LINC01643 — up, log2FC 2.40, p 0, adj. p 0TFF1 — up, log2FC 2.30, p 0, adj. p 0SLC22A31 — up, log2FC 2.30, p 0, adj. p 0LINC00853 — up, log2FC 2.30, p 0, adj. p 0PKP3 — up, log2FC 2.30, p 0, adj. p 0BIRC7 — up, log2FC 2.30, p 0, adj. p 0MESP2 — up, log2FC 2.30, p 0, adj. p 0GOLGA8M — up, log2FC 2.30, p 0, adj. p 0NPY5R — up, log2FC 2.30, p 0, adj. p 0TGIF2-RAB5IF — up, log2FC 2.30, p 0, adj. p 0SPRY4 — up, log2FC 2.30, p 0, adj. p 0LINC01162 — up, log2FC 2.30, p 0, adj. p 0SPATA31D3 — up, log2FC 2.30, p 0, adj. p 0INSIG1-DT — up, log2FC 2.30, p 0, adj. p 0KLRK1-AS1 — up, log2FC 2.30, p 0, adj. p 0SF1-DT — up, log2FC 2.30, p 0, adj. p 0MSANTD3-TMEFF1 — up, log2FC 2.20, p 0, adj. p 0HIPK4 — up, log2FC 2.20, p 0, adj. p 0ETV7 — up, log2FC 2.20, p 0, adj. p 0PYY — up, log2FC 2.20, p 0, adj. p 0C11ORF45 — up, log2FC 2.20, p 0, adj. p 0PABPC4L — up, log2FC 2.20, p 0, adj. p 0LINC02133 — up, log2FC 2.20, p 0, adj. p 0ENSG00000226659 — up, log2FC 2.20, p 0, adj. p 0LINC01754 — up, log2FC 2.20, p 0, adj. p 0DNAJC9-AS1 — up, log2FC 2.08, p 0, adj. p 0KCNK5 — up, log2FC 2.08, p 0FAM181B — up, log2FC 2.08, p 0, adj. p 0KCNJ8 — up, log2FC 2.08, p 0PLD5P1 — up, log2FC 2.08, p 0LNCTAM34A — up, log2FC 2.08, p 0, adj. p 0AKAP1-DT — up, log2FC 2.08, p 0, adj. p 0MST1R — up, log2FC 1.95, p 0, adj. p 0GPR182 — up, log2FC 1.95, p 0, adj. p 0RAG2 — up, log2FC 1.95, p 0, adj. p 0USP46-DT — up, log2FC 1.95, p 0, adj. p 0long intergenic non-protein coding rna 407 — up, log2FC 1.95, p 0, adj. p 0GRIK1-AS1 — up, log2FC 1.95, p 0, adj. p 0GML — up, log2FC 1.95, p 0, adj. p 0CLCA4 — up, log2FC 1.95, p 0, adj. p 0CNTFR — up, log2FC 1.95, p 0, adj. p 0TMEM225B — up, log2FC 1.95, p 0, adj. p 0CENATAC-DT — up, log2FC 1.95, p 0, adj. p 0MDFIC2 — up, log2FC 1.95, p 0, adj. p 0ANKRD44-AS1 — up, log2FC 1.95, p 0, adj. p 0MEIOSIN — up, log2FC 1.95, p 0, adj. p 0AMER3 — up, log2FC 1.95, p 0, adj. p 0LINC02233 — up, log2FC 1.95, p 0, adj. p 0LRRC8D-DT — up, log2FC 1.95, p 0, adj. p 0CCL24 — up, log2FC 1.79, p 0, adj. p 0FAM216B — up, log2FC 1.79, p 0, adj. p 0OXCT2 — up, log2FC 1.79, p 0MS4A6E — up, log2FC 1.79, p 0, adj. p 0LSMEM2 — up, log2FC 1.79, p 0, adj. p 0PARS2 — up, log2FC 1.79, p 0, adj. p 0SHISAL1 — up, log2FC 1.79, p 0, adj. p 0NBAT1 — up, log2FC 1.79, p 0, adj. p 0TRIM54 — up, log2FC 1.79, p 0, adj. p 0FAM25C — up, log2FC 1.79, p 0, adj. p 0H2BC10 — up, log2FC 1.79, p 0, adj. p 0C2CD4C — up, log2FC 1.79, p 0, adj. p 0TTC16 — up, log2FC 1.79, p 0, adj. p 0NETO1-DT — up, log2FC 1.79, p 0, adj. p 0LINC02470 — up, log2FC 1.79, p 0, adj. p 0FAM242A — up, log2FC 1.79, p 0, adj. p 0PARTICL — up, log2FC 1.79, p 0, adj. p 0LOC102724050 — up, log2FC 1.79, p 0, adj. p 0ITGA6-AS1 — up, log2FC 1.79, p 0, adj. p 0ADARB2-AS1 — up, log2FC 1.61, p 0, adj. p 0PSMA1 — up, log2FC 1.61, p 0, adj. p 0HOXC9 — up, log2FC 1.61, p 0, adj. p 0KRT15 — up, log2FC 1.61, p 0, adj. p 0CLEC3B — up, log2FC 1.61, p 0SPAG5-AS1 — up, log2FC 1.61, p 0HES5 — up, log2FC 1.61, p 0, adj. p 0PCSK9 — up, log2FC 1.61, p 0, adj. p 0NBR2 — up, log2FC 1.61, p 0PABPC5 — up, log2FC 1.61, p 0MRPS17 — up, log2FC 1.61, p 0, adj. p 0OR8K1 — up, log2FC 1.61, p 0, adj. p 0TCF15 — up, log2FC 1.61, p 0ZNF750 — up, log2FC 1.61, p 0, adj. p 0ADAMTSL4-AS1 — up, log2FC 1.61, p 0, adj. p 0SRARP — up, log2FC 1.61, p 0, adj. p 0TUNAR — up, log2FC 1.61, p 0, adj. p 0KL — up, log2FC 1.61, p 0, adj. p 0GPR158-AS1 — up, log2FC 1.61, p 0, adj. p 0FIBIN — up, log2FC 1.61, p 0, adj. p 0LINC01220 — up, log2FC 1.61, p 0, adj. p 0INKA2-AS1 — up, log2FC 1.61, p 0, adj. p 0GRTP1-AS1 — up, log2FC 1.61, p 0, adj. p 0SPIC — up, log2FC 1.61, p 0, adj. p 0FLRT1 — up, log2FC 1.61, p 0, adj. p 0MB — up, log2FC 1.61, p 0, adj. p 0HYMAI — up, log2FC 1.61, p 0, adj. p 0FHL5 — up, log2FC 1.61, p 0, adj. p 0SPACA5 — up, log2FC 1.61, p 0, adj. p 0LOC100506691 — up, log2FC 1.61, p 0CA3-AS1 — up, log2FC 1.61, p 0, adj. p 0ZNF516-AS1 — up, log2FC 1.61, p 0, adj. p 0CTXND1 — up, log2FC 1.61, p 0, adj. p 0LINC02495 — up, log2FC 1.61, p 0, adj. p 0GSG1L2 — up, log2FC 1.61, p 0, adj. p 0LINC01667 — up, log2FC 1.61, p 0, adj. p 0LINC02463 — up, log2FC 1.61, p 0, adj. p 0LINC02550 — up, log2FC 1.61, p 0, adj. p 0POLG-DT — up, log2FC 1.61, p 0ADRA1D — up, log2FC 1.39, p 0, adj. p 0CCKBR — up, log2FC 1.39, p 0, adj. p 0HOXA10 — up, log2FC 1.39, p 0IGFALS — up, log2FC 1.39, p 0HOXA4 — up, log2FC 1.39, p 0IGFBP1 — up, log2FC 1.39, p 0CYP26A1 — up, log2FC 1.39, p 0, adj. p 0ETV5-AS1 — up, log2FC 1.39, p 0, adj. p 0LINC00482 — up, log2FC 1.39, p 0, adj. p 0NANOS1 — up, log2FC 1.39, p 0PPP1R14D — up, log2FC 1.39, p 0, adj. p 0SCX — up, log2FC 1.39, p 0, adj. p 0HMHB1 — up, log2FC 1.39, p 0ARSH — up, log2FC 1.39, p 0, adj. p 0DUOXA1 — up, log2FC 1.39, p 0, adj. p 0ADAMTSL5 — up, log2FC 1.39, p 0, adj. p 0TMEM105 — up, log2FC 1.39, p 0, adj. p 0LINC00654 — up, log2FC 1.39, p 0, adj. p 0JMJD1C-AS1 — up, log2FC 1.39, p 0, adj. p 0LAMTOR5-AS1 — up, log2FC 1.39, p 0DLG1-AS1 — up, log2FC 1.39, p 0, adj. p 0ASPRV1 — up, log2FC 1.39, p 0, adj. p 0CCDC42B — up, log2FC 1.39, p 0, adj. p 0NPIPA8 — up, log2FC 1.39, p 0, adj. p 0C19ORF84 — up, log2FC 1.39, p 0, adj. p 0LINC01016 — up, log2FC 1.39, p 0, adj. p 0RBFADN — up, log2FC 1.39, p 0, adj. p 0LINC01231 — up, log2FC 1.39, p 0, adj. p 0LINC01248 — up, log2FC 1.39, p 0, adj. p 0RNF223 — up, log2FC 1.39, p 0, adj. p 0ARAP1-AS2 — up, log2FC 1.39, p 0, adj. p 0FGF10-AS1 — up, log2FC 1.39, p 0, adj. p 0LHB — up, log2FC 1.39, p 0, adj. p 0KIF25 — up, log2FC 1.39, p 0, adj. p 0LINC02740 — up, log2FC 1.39, p 0, adj. p 0LINC02733 — up, log2FC 1.39, p 0, adj. p 0LINC01908 — up, log2FC 1.39, p 0, adj. p 0LINC01825 — up, log2FC 1.39, p 0, adj. p 0LINC02540 — up, log2FC 1.39, p 0, adj. p 0LOC101927164 — up, log2FC 1.39, p 0, adj. p 0LINC01806 — up, log2FC 1.39, p 0PINCR — up, log2FC 1.39, p 0, adj. p 0LINC01514 — up, log2FC 1.39, p 0, adj. p 0LINC02446 — up, log2FC 1.39, p 0LINC01527 — up, log2FC 1.39, p 0, adj. p 0SH3TC2-DT — up, log2FC 1.39, p 0, adj. p 0LINC02610 — up, log2FC 1.39, p 0LOC645967 — up, log2FC 1.39, p 0SDAD1-AS1 — up, log2FC 1.39, p 0, adj. p 0LOC102725191 — up, log2FC 1.39, p 0, adj. p 0LOC105369911 — up, log2FC 1.39, p 0, adj. p 0RCCD1-AS1 — up, log2FC 1.39, p 0, adj. p 0 N sources0GABRB1 log2FC+2.75Best Adj. p2.4e-3DirectionUP (concordance not assessed — no sources) DE value present, no source provenance **GABRB1** has a recorded differential-expression value in **alzheimer's disease** (up, mean log2FC 2.75, best p-value 5.069205E-4 (raw)) — the same figure plotted in the volcano above — but zero corroborating sources are listed for it. This is deliberately NOT promoted to "detected" DE: a p-value with no listed source has no provenance to stand on. It is also deliberately not "absent" — there is a real recorded value, just an unconfirmed one. Treat this as a number to verify, not evidence to build a case on. C-DE-01.detected\_unsourced · 2 evidence refs de magnitudeup-regulated, mean log2FC 2.750.92 best pvaluebest p = 5.069205E-4 (raw), adjusted p = 0.0024432597 ### 8Mechanistic Chain DEFAULT 6-layer Sankey · Gene → Pathway → Cell Function → Tissue Function → Phenotype → Disease Theme 1: CNS phenotypes & seizures (70%) · 9 themes on this chart · 0 / 4 layers strictly convergent Themes: CNS phenotypes & seizures (70%) Default (no cell type)glutamatergic neuronastrocytesgabaergic neuronscentral nervous system neuroninterneuronsShowing: glutamatergic neuron GENEPATHWAYDivergentCELL FUNCTIONGene-onlyTISSUE FUNCTIONStructuralPHENOTYPEGene-onlyDISEASEGABRB1GABRB1Gaba receptor signalingGaba receptor signalingMbdnf and probdnf regul…Mbdnf and probdnf regulation of gaba neurotransmissionSignaling by erbb4Signaling by erbb4synaptic transmission, …synaptic transmission, GABAergicchloride transmembrane …chloride transmembrane transportFan embryonic ctx astro…Fan embryonic ctx astrocyte 1Fan embryonic ctx ex 4 …Fan embryonic ctx ex 4 excitatory neuronDescartes fetal placent…Descartes fetal placenta megakaryocytesHemostasisHemostasisCardiac conductionCardiac conductionTransport of bile salts…Transport of bile salts and organic acids metal ions and amine compoundssensory perception of s…sensory perception of soundmodulation of chemical …modulation of chemical synaptic transmissionEpileptic encephalopathyEpileptic encephalopathyEpileptic encephalopath…Epileptic encephalopathy (HP:0200134)Cerebral visual impairm…Cerebral visual impairmentHypsarrhythmiaHypsarrhythmiaHypsarrhythmia (HP:0002…Hypsarrhythmia (HP:0002521)alzheimer's diseasealzheimer's disease Node color = mechanism theme. Solid edges carry direct evidence (membership, ontology adjacency, HPO annotation); dashed edges are held by a shared theme or by disease-program enrichment; dotted grey edges are low-weight bridges the pipeline authored to keep the chain continuous, not evidence. Dashed node border = gene- or disease-side only; dotted border = structural fallback. Hover or focus a node/edge for details; click to inspect. Press Escape to clear. spec v10.1 · builder 1.1.0 · rules v0.20.1 · snapshot 2026-06-11 Sankey mechanism chain for GABRB1 in alzheimer's disease, 5 nodes per layer, 9 mechanism themes detected. Dispersed mechanism A graph-connected path from **GABRB1** to **alzheimer's disease** exists (4 of 4 middle layers populated) but no single theme dominates — 11 themes are hit across the full scoring population — this can be a larger set than the topK nodes trimmed onto this chart, so this count and the diagram may not match — none above the convergence threshold. Path existence alone does not establish a validated mechanism — some populated layers may route through tissue-, development-, or pathway-remote nodes; deriving a coherent, disease-relevant therapeutic hypothesis from this chain is difficult without further triage. C-MEC-01.weak · 3 evidence refs · 1 counterargument dominant themeCNS phenotypes & seizures0.70 convergent layers0 of 4 layers convergent0.00 theme diversity11 themes in the full scoring population (not the rendered chart) Gene-side rich, disease-side weak 2 of the 4 middle layers are gene-only — the gene has pathway annotations there, but the disease's enriched programs don't include them. The gene's biology is well-characterised but the disease may not actually engage this part of it. Treat the connection as gene-side speculation pending disease-side validation. gene\_only\_chain · moderate ### 9Protein Networks DEFAULT Network source PPI · STRING / SIGNOR Signalling · Reactome Co-expression · ARCHS4 TF-target · TFLink External source-specific tab (STRING/SIGNOR, Reactome, ARCHS4, or TFLink) is not available on this platform yet — the platform's own graph is shown below instead. 1 hop2 hopsGABRB1SP1GABRA1GABRA2GABRA3GABRA4GABRA5GABRA6GABRG2GABRG3GABRQSTAT5AFOXA1STAT3TEAD1HSF2RELANRG2ARHGEF9AGT Selected geneDirect interactor & disease seedDisease seedClinical drug targetReal 1-hop interactor Network probability (p\_network)0.03 Direct interactors31 Disease seeds200 Seeds within 1 hop1 Seeds within 2 hops65 Shortest hop to any seed1 hop Median hop to seed2 Show all 200 disease seeds - SYMPKtier 1 · weight 0.35 - RP11-551L14.1tier 1 · weight 0.35 - RPS2tier 1 · weight 0.35 - LIN7Btier 1 · weight 0.35 - CDC14Btier 1 · weight 0.35 - POFUT4tier 1 · weight 0.35 - LIMK2tier 1 · weight 0.35 - NDUFA4L2tier 1 · weight 0.35 - NECTIN2tier 1 · weight 0.35 - STX6tier 1 · weight 0.35 - PMS2P1tier 1 · weight 0.35 - NEFHtier 1 · weight 0.35 - RPS19P3tier 1 · weight 0.35 - LINC00094tier 1 · weight 0.35 - PNMA8Btier 1 · weight 0.35 - PNMA8Ctier 1 · weight 0.35 - ENSG00000262539tier 1 · weight 0.35 - LRP4tier 1 · weight 0.35 - RPSAP9tier 1 · weight 0.35 - NCK1tier 1 · weight 0.35 - ZC3H11Atier 1 · weight 0.35 - CD47tier 1 · weight 0.35 - HMSDtier 1 · weight 0.35 - POLR1Gtier 1 · weight 0.35 - CD8B2tier 1 · weight 0.35 - CDAN1tier 1 · weight 0.35 - NDUFA10tier 1 · weight 0.35 - GOLGA6L5tier 1 · weight 0.35 - ZAP70tier 1 · weight 0.35 - NDST1tier 1 · weight 0.35 - LILRB1tier 1 · weight 0.35 - AP1G1tier 1 · weight 0.35 - CD81tier 1 · weight 0.35 - CNTNAP1tier 1 · weight 0.35 - RPS6KL1tier 1 · weight 0.35 - POLR2Jtier 1 · weight 0.35 - NCOA7tier 1 · weight 0.35 - WNT2Btier 1 · weight 0.35 - NIP7tier 1 · weight 0.35 - PLEKHA1tier 1 · weight 0.35 - KANSL1-AS1tier 1 · weight 0.35 - CDK10tier 1 · weight 0.35 - BLNKtier 1 · weight 0.35 - BLOC1S3tier 1 · weight 0.35 - DHDDStier 1 · weight 0.35 - LLPH-DTtier 1 · weight 0.35 - LL22NC03-75H12.2tier 1 · weight 0.35 - FAM180Btier 1 · weight 0.35 - RP11-317J10.2tier 1 · weight 0.35 - KANK1tier 1 · weight 0.35 - NKPD1tier 1 · weight 0.35 - STK4tier 1 · weight 0.35 - ENSG00000287538tier 1 · weight 0.35 - ENSG00000288845tier 1 · weight 0.35 - STX12tier 1 · weight 0.35 - ACEtier 1 · weight 0.35 - STX3tier 1 · weight 0.35 - ENSG00000225867tier 1 · weight 0.35 - CDC42SE2tier 1 · weight 0.35 - PM20D1tier 1 · weight 0.35 - FUT9tier 1 · weight 0.35 - NELL1tier 1 · weight 0.35 - CDC42P6tier 1 · weight 0.35 - BIN1tier 1 · weight 0.35 - ENSG00000263698tier 1 · weight 0.35 - ENSG00000224415tier 1 · weight 0.35 - PLEKHM1tier 1 · weight 0.35 - CDCA5tier 1 · weight 0.35 - NF2tier 1 · weight 0.35 - DGCR11tier 1 · weight 0.35 - SMG9tier 1 · weight 0.35 - NFE2L2tier 1 · weight 0.35 - LRWD1tier 1 · weight 0.35 - ZNF155tier 1 · weight 0.35 - LRRN4tier 1 · weight 0.35 - ZNF19tier 1 · weight 0.35 - RP11-105C19.1tier 1 · weight 0.35 - ZMYM4tier 1 · weight 0.35 - ENSG00000232949tier 1 · weight 0.35 - TNS3tier 1 · weight 0.35 - MYH10tier 1 · weight 0.35 - ZNF112tier 1 · weight 0.35 - CCT2tier 1 · weight 0.35 - ENSG00000233175tier 1 · weight 0.35 - FOLH1tier 1 · weight 0.35 - CYP21A1Ptier 1 · weight 0.35 - ZNF233tier 1 · weight 0.35 - ZNF234tier 1 · weight 0.35 - ZNF235tier 1 · weight 0.35 - SLC35G2tier 1 · weight 0.35 - CYBC1tier 1 · weight 0.35 - ENSG00000235979tier 1 · weight 0.35 - MTCH2tier 1 · weight 0.35 - CYCSP40tier 1 · weight 0.35 - BAXtier 1 · weight 0.35 - MTND2P28tier 1 · weight 0.35 - CORO1Btier 1 · weight 0.35 - ZNF225tier 1 · weight 0.35 - RP1-39G22.7tier 1 · weight 0.35 - ZNF224tier 1 · weight 0.35 - SLC39A13tier 1 · weight 0.35 - LBHD2tier 1 · weight 0.35 - ENSG00000287449tier 1 · weight 0.35 - EPHX4tier 1 · weight 0.35 - BCL3tier 1 · weight 0.35 - CD2AP-DTtier 1 · weight 0.35 - LRRC37Atier 1 · weight 0.35 - NAIF1tier 1 · weight 0.35 - SUV39H2tier 1 · weight 0.35 - KCNK13tier 1 · weight 0.35 - ENSG00000230699tier 1 · weight 0.35 - ENSG00000230825tier 1 · weight 0.35 - LRRC37A2tier 1 · weight 0.35 - RTN2tier 1 · weight 0.35 - LRRC37A4Ptier 1 · weight 0.35 - ENSG00000230606tier 1 · weight 0.35 - AP4M1tier 1 · weight 0.35 - NBEAL1tier 1 · weight 0.35 - NARFtier 1 · weight 0.35 - AC103563.8tier 1 · weight 0.35 - NARF-AS2tier 1 · weight 0.35 - CD33tier 1 · weight 0.35 - AC104534.2tier 1 · weight 0.35 - ENSG00000272906tier 1 · weight 0.35 - ZCWPW1tier 1 · weight 0.35 - ENSG00000261543tier 1 · weight 0.35 - RP11-11N9.4tier 1 · weight 0.35 - PPP1R37tier 1 · weight 0.35 - DARStier 1 · weight 0.35 - ENSG00000261575tier 1 · weight 0.35 - COMMD10tier 1 · weight 0.35 - DANCRtier 1 · weight 0.35 - ZKSCAN1tier 1 · weight 0.35 - ZKSCAN5tier 1 · weight 0.35 - SYCE1Ltier 1 · weight 0.35 - AC093391.2tier 1 · weight 0.35 - NAA80tier 1 · weight 0.35 - C4Atier 1 · weight 0.35 - ERCC2tier 1 · weight 0.35 - ERCC1tier 1 · weight 0.35 - RP11-13P5.1tier 1 · weight 0.35 - PPM1Ntier 1 · weight 0.35 - ENSG00000273015tier 1 · weight 0.35 - ENSG00000227141tier 1 · weight 0.35 - APOC2tier 1 · weight 0.35 - APOC1tier 1 · weight 0.35 - APOC1P1tier 1 · weight 0.35 - MYPOPtier 1 · weight 0.35 - RUFY4tier 1 · weight 0.35 - EGFRtier 1 · weight 0.35 - ENSG00000268401tier 1 · weight 0.35 - USP6NLtier 1 · weight 0.35 - PDFtier 1 · weight 0.35 - LINC02210tier 1 · weight 0.35 - OSBPtier 1 · weight 0.35 - LINC02091tier 1 · weight 0.35 - SRA1tier 1 · weight 0.35 - PDAP1tier 1 · weight 0.35 - AL928768.3tier 1 · weight 0.35 - RP11-529F4.1tier 1 · weight 0.35 - SP1tier 1 · weight 0.35on canvas - SP100tier 1 · weight 0.35 - ENSG00000288062tier 1 · weight 0.35 - LINC02094tier 1 · weight 0.35 - ENSG00000280022tier 1 · weight 0.35 - CIPCtier 1 · weight 0.35 - SNX6tier 1 · weight 0.35 - BSN-DTtier 1 · weight 0.35 - INPP5Etier 1 · weight 0.35 - EIF2S2P3tier 1 · weight 0.35 - BSPRYtier 1 · weight 0.35 - ALOX12tier 1 · weight 0.35 - HLA-DMAtier 1 · weight 0.35 - HLA-DMBtier 1 · weight 0.35 - OPA3tier 1 · weight 0.35 - TUFMtier 1 · weight 0.35 - OOSP1tier 1 · weight 0.35 - OOSP4Atier 1 · weight 0.35 - CEP85tier 1 · weight 0.35 - GIPRtier 1 · weight 0.35 - TUBB8P7tier 1 · weight 0.35 - ALG3tier 1 · weight 0.35 - UHRF2tier 1 · weight 0.35 - ENSG00000270001tier 1 · weight 0.35 - IRF2BP1tier 1 · weight 0.35 - ECE2tier 1 · weight 0.35 - GEMIN8P4tier 1 · weight 0.35 - AKAP11tier 1 · weight 0.35 - C11orf24tier 1 · weight 0.35 - ENSG00000269984tier 1 · weight 0.35 - SPIRE2tier 1 · weight 0.35 - IQGAP1tier 1 · weight 0.35 - RP11-645C24.5tier 1 · weight 0.35 - PCMTD2tier 1 · weight 0.35 - INVStier 1 · weight 0.35 - ENSG00000270321tier 1 · weight 0.35 - RP11-572M11.4tier 1 · weight 0.35 - CFAP276tier 1 · weight 0.35 - BTNL2tier 1 · weight 0.35 - PRKD3tier 1 · weight 0.35 All direct interactors (31) - SP1on canvas - GABRA1on canvas - GABRA2on canvas - GABRA3on canvas - GABRA4on canvas - GABRA5on canvas - GABRA6on canvas - GABRG2on canvas - GABRG3on canvas - GABRQon canvas - STAT5Aon canvas - FOXA1on canvas - STAT3on canvas - TEAD1on canvas - HSF2on canvas - RELAon canvas - NRG2on canvas - ARHGEF9on canvas - AGTon canvas - NEUROD4 - UBQLN1 - TCF3 - POU2F1 - CUL1 - ERBB4 - NOD1 - NPTN - SMAD1 - NRF1 - HSPA8 - EGR4 All approved / clinical anchors (150) - ABL1clinical - ADORA1clinical - ADORA2Aclinical - ADORA2Bclinical - ADORA3clinical - AGERclinical - APH1Aclinical - APPapproved - ATP4Aclinical - BACE1clinical - BCHEapproved - CACNA1Bclinical - CACNA1Cclinical - CACNA1Dclinical - CD38clinical - CETPclinical - CHRM2clinical - CHRNA4clinical - CHRNA5clinical - CHRNA6clinical - CHRNA7clinical - CHRNB2clinical - CNR1clinical - CRBNclinical - CSF2RBclinical - DRD1clinical - DRD2clinical - DRD4clinical - EPHA2clinical - ESR1clinical - ESR2clinical - FGFR3clinical - FKBP1Aclinical - FRKclinical - FYNclinical - GABBR1clinical - GABBR2clinical - GABRA1clinicalon canvas - GABRA2clinicalon canvas - GABRDclinical - GLP1Rclinical - GNRHRclinical - GRIN2Aapproved - GRIN2Bapproved - GRIN2Capproved - GRIN2Dapproved - GRIN3Aapproved - GRIN3Bapproved - GSK3Bclinical - GUCY1A1clinical - HCRTR2clinical - HDAC1clinical - HDAC2clinical - HDAC3clinical - HMGCRclinical - HTR1Aclinical - HTR2Aclinical - HTR3Aclinical - HTR3Bclinical - HTR6clinical - IL2RAclinical - INSRclinical - KITclinical - LCKclinical - LYNclinical - MAPK14clinical - MAPTclinical - MMP1clinical - MMP8clinical - NCSTNclinical - PDE4Dclinical - PDE5Aclinical - PDE9Aclinical - PDGFRBclinical - PGRclinical - PLA2G7clinical - PPARDclinical - PPARGclinical - PSEN1clinical - PSEN2clinical - PSENENclinical - PTGS2clinical - RARAclinical - RARBclinical - RARGclinical - RXRAclinical - RXRBclinical - SCN11Aclinical - SCN1Aclinical - SCN3Aclinical - SCN4Aclinical - SCN5Aclinical - SCN7Aclinical - SCN8Aclinical - SCN9Aclinical - SEMA4Dclinical - SERPINE1clinical - SLC5A2clinical - SRCclinical - TNFclinical - VDRclinical - YES1clinical - ACHEapproved - GRIN1approved - ADRA2Cclinical - AGTR1clinical - ATP4Bclinical - CACNA1Fclinical - CACNA1Sclinical - CHRM1clinical - CHRM3clinical - DRD3clinical - GABRA3clinicalon canvas - GABRA4clinicalon canvas - GABRA5clinicalon canvas - GABRA6clinicalon canvas - GABRB1clinicalon canvas - GABRB2clinical - GABRB3clinical - GABREclinical - GABRG1clinical - GABRG2clinicalon canvas - GABRG3clinicalon canvas - GABRPclinical - GABRQclinicalon canvas - GRIA1clinical - GRIA2clinical - GRIA3clinical - GRIA4clinical - GSK3Aclinical - GUCY1B1clinical - HCRTR1clinical - HDAC6clinical - HRH3clinical - HSD11B1clinical - HTR2Cclinical - HTR3Cclinical - HTR3Dclinical - HTR3Eclinical - HTR4clinical - MAOBclinical - MMP13clinical - MMP7clinical - PDGFRAclinical - RXRGclinical - SCN10Aclinical - SCN2Aclinical - SLC6A2clinical - SLC6A3clinical - SLC6A4clinical Network proximity score below the calibrated cutoff **GABRB1** scored 0.028 on the Layer-1 RWR network expert — below the moderate-band threshold (connected threshold 0.1 (~p75), moderate threshold 0.04 (~p50) of the background RWR-score distribution across target-disease pairs — restart probability, seed weighting, and per-pair uncertainty are not exposed by this pipeline; this score is not compared against a negative-control distribution). The disease registry names 200 disease-associated genes in the network registry (list capped at 200 — the true count may be higher) for **alzheimer's disease**, so the anchor set is meaningful, but the gene's RWR score falls below the calibrated cutoff. The genetic case may still hold via mechanisms not captured by the curated network (e.g. metabolic cascades, ligand-receptor pairs outside STRING/SIGNOR), but the network axis pushes against the gene–disease link rather than for it. C-NET-01.isolated · 2 evidence refs network expert signalp\_network = 0.028 (connected threshold 0.1 ≈ p75, moderate threshold 0.04 ≈ p50 of the background RWR-score distribution — restart probability, seed weighting, and per-pair uncertainty are not exposed by this pipeline)0.11 disease seed anchor set200 causal seed(s) anchor the disease1.00 DATA SOURCE Platform knowledge graph Not STRING/SIGNOR, Reactome, ARCHS4, or TFLink data. The canvas shows real 1-hop/2-hop graph interactors, disease causal seeds, clinical/approved drug-target anchors, and reported transcription factors, ranked and connected by relationships from the platform's own knowledge graph, bounded to a 2-hop search. C-NET-01 · real hop search + curated seeds/drug-targets · platform knowledge graph · snapshot 2026-06-11 ### 10Phenotypes DEFAULT HPO overlap — GABRB1 phenotype profile IC-weighted HPO terms (Phenomizer-style), ranked by prevalence across the gene's known disease overlaps seizures 1,080 dis · IC 7.0 global developmental delay 920 dis · IC 6.3 muscle hypotonia 798 dis · IC 6.9 infantile onset 549 dis · IC 6.9 ataxia 455 dis · IC 8.1 autosomal dominant inheritance 379 dis · IC 6.3 hypoplasia of corpus callosum 351 dis · IC 8.9 developmental regression 214 dis · IC 9.5 Shared with selected disease GABRB1-annotated, not shared with selected disease GABRB1 disease overlaps 1,533 GABRB1 × alzheimer's disease no HPO data GABRB1 top match (DOID:0080139) 12 HPO · IC 111.1 curated Every term on this panel comes from curated HPO annotation — there is no literature-derived phenotype evidence in this panel. HPO curates roughly 5,250 of ~20,000 human genes, so an empty panel means this source does not cover GABRB1, not that no phenotype association has been reported for it. No phenotypic overlap data No HPO phenotype overlap could be computed for **GABRB1** × **alzheimer's disease**. Only ~5,250 of ~20K human genes have curated HPO annotations, and only ~9,400 of ~34K registered diseases have an HPO profile, so a meaningful fraction of pairs lack overlap data entirely. The phenotype axis is silent here — neither supporting nor opposing the case. C-PHE-01.absent · 1 absence **Phenotype overlap not computed.** The gene has no curated HPO annotations, the disease has no HPO profile in the registry, or the alias bridge missed (HPO uses OMIM / ORPHA IDs; the TPS spine uses MONDO / DOID). The phenotype axis cannot contribute to the synthesis verdict for this pair. no\_phenotype\_overlap · weakens matchedcross-disease · context, not a claim GABRB1 top phenotype match (DOID:0080139) multiple congenital anomalies-hypotonia-seizures syndrome 2 (DOID:0080139) Shared HPO12 IC score111.1 Max IC11.90 Jaccard0.050 GABRB1 and multiple congenital anomalies-hypotonia-seizures syndrome 2 share 12 HPO terms with IC score 111.1 (best single-term IC 11.90, Jaccard 0.050). Information Content gives more weight to specific phenotypes and downweights generic terms. The selected disease has no HPO profile to compare against, so this is the gene's best match against a DIFFERENT disease — exploratory context only. It does not change the selected pair's score or claim state, and is not evidence for the gene-disease pair on this page. Top shared HPO terms (5) aplasia/hypoplasia of the corpus callosum (HP:0007370)IC 11.90 Obligate HPO frequency band: Obligate = 100% of affected individuals. Read from the curated annotation's HPO frequency code. abnormality of the cerebral white matter (HP:0002500)IC 11.04 Obligate HPO frequency band: Obligate = 100% of affected individuals. Read from the curated annotation's HPO frequency code. infantile spasms (HP:0002521)IC 10.74 Obligate HPO frequency band: Obligate = 100% of affected individuals. Read from the curated annotation's HPO frequency code. visual cortical disorder (HP:0100704)IC 10.69 Obligate HPO frequency band: Obligate = 100% of affected individuals. Read from the curated annotation's HPO frequency code. encephalopathies (HP:0001298)IC 10.68 Obligate HPO frequency band: Obligate = 100% of affected individuals. Read from the curated annotation's HPO frequency code. ### 11Literature DEFAULT GABRB1 × alzheimer's disease co-mention trend (2022 – 2023) PubMed co-mentions · landmark papers tagged from max(cited\_by) on the platform's own PubMed citation index 01220222023Landmark (29 citations) Total3 20260 Reviews0 GeneRIFs0 Top-cited papers (landmark identification by max(cited\_by)) — deterministic; platform's own PubMed citation index, not LLM | Year | Journal | Cited by | Title | | --- | --- | --- | --- | | 2022 | Translational psychiatry | 29 | [Differential microRNA expression analyses across two brain regions in Alzheimer's disease.](https://ask.euretos.com/publication-details/110757735) | | 2022 | Brain research | 6 | [Brain injury and inflammation genes common to a number of neurological diseases and the genes involved in the genesis of GABAnergic neurons are altered in monoamine oxidase B knockout mice.](https://ask.euretos.com/publication-details/109520699) | | 2023 | Open Targets | 0 | [Open Targets/ENSG00000163288::MONDO\_0004975](https://ask.euretos.com/publication-details/71142493) | Top-5 papers carry 100% of total citations. Essentially un-published as a pair PubMed co-mentions for **GABRB1** × **alzheimer's disease** are below the emerging threshold (or absent entirely). The literature axis is silent — no published claim either supports or opposes the pair. This is the typical state for novel TPS-discovered pairs and is not a negative signal in itself; the case rests on the upstream causal, mechanistic, and translational axes. C-LIT-01.absent DATA SOURCE Platform's PubMed co-mention + citation index Computed at request time from the platform's own PubMed co-mention graph: total co-mentioning papers, papers in the last 3 years, the most-cited paper's citation count, and the citation share held by the top 5 papers. Exact-concept co-mention: a paper counts only if the gene AND disease concepts are both linked to it — no broadening to parent/child disease terms at request time. C-LIT-01 ### 12Clinical Trials DEFAULT Trial phase timeline — GABRB1 direct + mechanism-adjacent (PPI 1-hop, Reactome pathway co-members) Source: AACT trial registry × drug-target mappings × PPI/pathway adjacency, snapshot 2026-06-10 GABRB1 — Brasilia University Hospital Zolpidem GABRA1 — Brasilia University Hospital Zolpidem GABRG2 — Brasilia University Hospital Zolpidem GABRA2 — Mayo Clinic lorazepam GABRA3 — Mayo Clinic lorazepam P3P3P3P1P120132016 Direct GABRB1 programs4 Mechanism-adjacent programs44 Active (any phase)0 Completed48 Discontinued0 Direct max phasePhase 3 Adjacent max phase Phase 3 DATA SOURCE AACT clinical trials registry 579K studies, refreshed weekly. Per-pair trial roll-up Combines the AACT trial registry with drug-target mappings, STRING protein-protein interactions, and Reactome pathway adjacency to link trials to a gene × disease pair. Snapshot 2026-06-10, covering 11K genes × 2K diseases. C-CMP-01 Saturated competitive landscape **GABRB1** sits in a saturated field — 38 drugs (any indication), 2 approved, 10 in clinical (VERY\_HIGH competition). The target is mature: entry requires a strong differentiation thesis (novel modality, underserved indication, biomarker-stratified subpopulation, combination strategy). Saturated is not a no-go — but the commercial bar is high. C-CMP-01.saturated · 6 evidence refs competition levelVERY\_HIGH drug count38 drugs (2 approved, 10 in clinical, 0 failed)1.00 validation levelAPPROVED opportunity assessmentHighly crowded (38 drugs: 2 approved, 10 in clinical trials) - differentiation critical - validated target direct clinical precedent4 direct program(s), max phase phase\_3 (0 active, 48 completed, 0 discontinued)0.20 adjacent clinical precedent44 adjacent program(s) (PPI 1-hop or pathway co-member), max phase phase\_3 (adjacent-mechanism evidence, not direct target validation)0.88 ### 13Protein Structure DEFAULT Domain architecture · GABRB1 (474 aa) Neurotransmitter-gated ion-channel ligand-binding domain, Neurotransmitter-gated ion-channel transmembrane domain Length474 aa PDB9CXB AlphaFoldAF-P18505-F1 Protein 2D structure Annotated sequence features and experimental proteomic data in the context of protein topology — image generated by Protter (Omasits et al., Bioinformatics 2014). PNG SVG generated using ProtterExtracellularCytoplasmicMet1: signal peptideMet1: signal peptideTrp2: signal peptideTrp2: signal peptideThr3: signal peptideThr3: signal peptideVal4: signal peptideVal4: signal peptideGln5: signal peptideGln5: signal peptideAsn6: signal peptideAsn6: signal peptideArg7: signal peptideArg7: signal peptideGlu8: signal peptideGlu8: signal peptideSer9: signal peptideSer9: signal peptideLeu10: signal peptideLeu10: signal peptide10Gly11: signal peptideGly11: signal peptideLeu12: signal peptideLeu12: signal peptideLeu13: signal peptideLeu13: signal peptideSer14: signal peptideSer14: signal peptidePhe15: signal peptidePhe15: signal peptidePro16: signal peptidePro16: signal peptideVal17: signal peptideVal17: signal peptideMet18: signal peptideMet18: signal peptideIle19: signal peptideIle19: signal peptideThr20: signal peptideThr20: signal peptide20Met21: signal peptideMet21: signal peptideVal22: signal peptideVal22: signal peptideCys23: signal peptideCys23: signal peptideCys24: signal peptideCys24: signal peptideAla25: signal peptideAla25: signal peptideHis26His26Ser27Ser27Thr28Thr28Asn29Asn29Glu30Glu3030Pro31Pro31Ser32Ser32Asn33Asn33Met34Met34Ser35Ser35Tyr36Tyr36Val37Val37Lys38Lys38Glu39Glu39Thr40Thr4040Val41Val41Asp42Asp42Arg43Arg43Leu44Leu44Leu45Leu45Lys46Lys46Gly47Gly47Tyr48Tyr48Asp49Asp49Ile50Ile5050Arg51Arg51Leu52Leu52Arg53Arg53Pro54Pro54Asp55Asp55Phe56Phe56Gly57Gly57Gly58Gly58Pro59Pro59Pro60Pro6060Val61Val61Asp62Asp62Val63Val63Gly64Gly64Met65Met65Arg66Arg66Ile67Ile67Asp68Asp68Val69Val69Ala70Ala7070Ser71Ser71Ile72Ile72Asp73Asp73Met74Met74Val75Val75Ser76Ser76Glu77Glu77Val78Val78Asn79Asn79Met80Met8080Asp81Asp81Tyr82Tyr82Thr83Thr83Leu84Leu84Thr85Thr85Met86Met86Tyr87Tyr87Phe88Phe88Gln89Gln89Gln90Gln9090Ser91Ser91Trp92Trp92Lys93Lys93Asp94Asp94Lys95Lys95Arg96Arg96Leu97Leu97Ser98Ser98Tyr99Tyr99Ser100Ser100100Gly101Gly101Ile102Ile102Pro103Pro103Leu104Leu104Asn105: PTMsAsn105: PTMsLeu106Leu106Thr107Thr107Leu108Leu108Asp109Asp109Asn110Asn110110Arg111Arg111Val112Val112Ala113Ala113Asp114Asp114Gln115Gln115Leu116Leu116Trp117Trp117Val118Val118Pro119Pro119Asp120Asp120120Thr121Thr121Tyr122Tyr122Phe123Phe123Leu124Leu124Asn125Asn125Asp126Asp126Lys127Lys127Lys128Lys128Ser129Ser129Phe130Phe130130Val131Val131His132His132Gly133Gly133Val134Val134Thr135Thr135Val136Val136Lys137Lys137Asn138Asn138Arg139Arg139Met140Met140140Ile141Ile141Arg142Arg142Leu143Leu143His144His144Pro145Pro145Asp146Asp146Gly147Gly147Thr148Thr148Val149Val149Leu150Leu150150Tyr151Tyr151Gly152Gly152Leu153Leu153Arg154Arg154Ile155Ile155Thr156Thr156Thr157Thr157Thr158Thr158Ala159Ala159Ala160Ala160160Cys161: disulfide bondsCys161: disulfide bondsMet162Met162Met163Met163Asp164Asp164Leu165Leu165Arg166Arg166Arg167Arg167Tyr168Tyr168Pro169Pro169Leu170Leu170170Asp171Asp171Glu172Glu172Gln173Gln173Asn174: PTMsAsn174: PTMsCys175: disulfide bondsCys175: disulfide bondsThr176Thr176Leu177Leu177Glu178Glu178Ile179Ile179Glu180Glu180180Ser181Ser181Tyr182Tyr182Gly183Gly183Tyr184Tyr184Thr185Thr185Thr186Thr186Asp187Asp187Asp188Asp188Ile189Ile189Glu190Glu190190Phe191Phe191Tyr192Tyr192Trp193Trp193Asn194Asn194Gly195Gly195Gly196Gly196Glu197Glu197Gly198Gly198Ala199Ala199Val200Val200200Thr201Thr201Gly202Gly202Val203Val203Asn204Asn204Lys205Lys205Ile206Ile206Glu207Glu207Leu208Leu208Pro209Pro209Gln210Gln210210Phe211Phe211Ser212Ser212Ile213Ile213Val214Val214Asp215Asp215Tyr216Tyr216Lys217Lys217Met218Met218Val219Val219Ser220Ser220220Lys221Lys221Lys222Lys222Val223Val223Glu224Glu224Phe225: Binding SitePhe225: Binding SiteThr226Thr226Thr227Thr227Gly228Gly228Ala229Ala229Tyr230Tyr230230Pro231Pro231Arg232Arg232Leu233Leu233Ser234Ser234Leu235Leu235Ser236Ser236Phe237Phe237Arg238Arg238Leu239Leu239Lys240Lys240240Arg241Arg241Asn242Asn242Ile243Ile243Gly244Gly244Tyr245Tyr245Phe246: variants & Transmembrane domainPhe246: variants & Transmembrane domainIle247: Transmembrane domainIle247: Transmembrane domainLeu248: Transmembrane domainLeu248: Transmembrane domainGln249: Transmembrane domainGln249: Transmembrane domainThr250: Transmembrane domainThr250: Transmembrane domain250Tyr251: Transmembrane domainTyr251: Transmembrane domainMet252: Transmembrane domainMet252: Transmembrane domainPro253: Transmembrane domainPro253: Transmembrane domainSer254: Transmembrane domainSer254: Transmembrane domainThr255: Transmembrane domainThr255: Transmembrane domainLeu256: Transmembrane domainLeu256: Transmembrane domainIle257: Transmembrane domainIle257: Transmembrane domainThr258: Transmembrane domainThr258: Transmembrane domainIle259: Transmembrane domainIle259: Transmembrane domainLeu260: Transmembrane domainLeu260: Transmembrane domain260Ser261: Transmembrane domainSer261: Transmembrane domainTrp262: Transmembrane domainTrp262: Transmembrane domainVal263: Transmembrane domainVal263: Transmembrane domainSer264: Transmembrane domainSer264: Transmembrane domainPhe265: Transmembrane domainPhe265: Transmembrane domainTrp266: Transmembrane domainTrp266: Transmembrane domainIle267: Transmembrane domainIle267: Transmembrane domainAsn268Asn268Tyr269Tyr269Asp270Asp270270Ala271: Transmembrane domainAla271: Transmembrane domainSer272: Transmembrane domainSer272: Transmembrane domainAla273: Transmembrane domainAla273: Transmembrane domainAla274: Transmembrane domainAla274: Transmembrane domainArg275: Transmembrane domainArg275: Transmembrane domainVal276: Transmembrane domainVal276: Transmembrane domainAla277: Transmembrane domainAla277: Transmembrane domainLeu278: Transmembrane domainLeu278: Transmembrane domainGly279: Transmembrane domainGly279: Transmembrane domainIle280: Transmembrane domainIle280: Transmembrane domain280Thr281: Transmembrane domainThr281: Transmembrane domainThr282: Transmembrane domainThr282: Transmembrane domainVal283: Transmembrane domainVal283: Transmembrane domainLeu284: Transmembrane domainLeu284: Transmembrane domainThr285: Transmembrane domainThr285: Transmembrane domainMet286: Transmembrane domainMet286: Transmembrane domainThr287: variants & Transmembrane domainThr287: variants & Transmembrane domainThr288: Transmembrane domainThr288: Transmembrane domainIle289: Transmembrane domainIle289: Transmembrane domainSer290: Transmembrane domainSer290: Transmembrane domain290Thr291: Transmembrane domainThr291: Transmembrane domainHis292: Transmembrane domainHis292: Transmembrane domainLeu293: Transmembrane domainLeu293: Transmembrane domainArg294Arg294Glu295Glu295Thr296Thr296Leu297Leu297Pro298Pro298Lys299Lys299Ile300Ile300300Pro301Pro301Tyr302Tyr302Val303Val303Lys304Lys304Ala305: Transmembrane domainAla305: Transmembrane domainIle306: Transmembrane domainIle306: Transmembrane domainAsp307: Transmembrane domainAsp307: Transmembrane domainIle308: Transmembrane domainIle308: Transmembrane domainTyr309: Transmembrane domainTyr309: Transmembrane domainLeu310: Transmembrane domainLeu310: Transmembrane domain310Met311: Transmembrane domainMet311: Transmembrane domainGly312: Transmembrane domainGly312: Transmembrane domainCys313: Transmembrane domainCys313: Transmembrane domainPhe314: Transmembrane domainPhe314: Transmembrane domainVal315: Transmembrane domainVal315: Transmembrane domainPhe316: Transmembrane domainPhe316: Transmembrane domainVal317: Transmembrane domainVal317: Transmembrane domainPhe318: Transmembrane domainPhe318: Transmembrane domainLeu319: Transmembrane domainLeu319: Transmembrane domainAla320: Transmembrane domainAla320: Transmembrane domain320Leu321: Transmembrane domainLeu321: Transmembrane domainLeu322: Transmembrane domainLeu322: Transmembrane domainGlu323: Transmembrane domainGlu323: Transmembrane domainTyr324: Transmembrane domainTyr324: Transmembrane domainAla325: Transmembrane domainAla325: Transmembrane domainPhe326: Transmembrane domainPhe326: Transmembrane domainVal327: Transmembrane domainVal327: Transmembrane domainAsn328Asn328Tyr329Tyr329Ile330Ile330330Phe331Phe331Phe332Phe332Gly333Gly333Lys334Lys334Gly335Gly335Pro336Pro336Gln337Gln337Lys338Lys338Lys339Lys339Gly340Gly340340Ala341Ala341Ser342Ser342Lys343Lys343Gln344Gln344Asp345Asp345Gln346Gln346Ser347Ser347Ala348Ala348Asn349Asn349Glu350Glu350350Lys351Lys351Asn352Asn352Lys353Lys353Leu354Leu354Glu355Glu355Met356Met356Asn357Asn357Lys358Lys358Val359Val359Gln360Gln360360Val361Val361Asp362Asp362Ala363Ala363His364His364Gly365Gly365Asn366Asn366Ile367Ile367Leu368Leu368Leu369Leu369Ser370Ser370370Thr371Thr371Leu372Leu372Glu373Glu373Ile374Ile374Arg375Arg375Asn376Asn376Glu377Glu377Thr378Thr378Ser379Ser379Gly380Gly380380Ser381Ser381Glu382Glu382Val383Val383Leu384Leu384Thr385Thr385Ser386Ser386Val387Val387Ser388Ser388Asp389Asp389Pro390Pro390390Lys391Lys391Ala392Ala392Thr393Thr393Met394Met394Tyr395Tyr395Ser396Ser396Tyr397Tyr397Asp398Asp398Ser399Ser399Ala400Ala400400Ser401Ser401Ile402Ile402Gln403Gln403Tyr404Tyr404Arg405Arg405Lys406Lys406Pro407Pro407Leu408Leu408Ser409Ser409Ser410Ser410410Arg411Arg411Glu412Glu412Ala413Ala413Tyr414Tyr414Gly415Gly415Arg416Arg416Ala417Ala417Leu418Leu418Asp419Asp419Arg420Arg420420His421: variantsHis421: variantsGly422Gly422Val423Val423Pro424Pro424Ser425Ser425Lys426Lys426Gly427Gly427Arg428Arg428Ile429: variantsIle429: variantsArg430Arg430430Arg431Arg431Arg432Arg432Ala433Ala433Ser434Ser434Gln435Gln435Leu436Leu436Lys437Lys437Val438Val438Lys439Lys439Ile440Ile440440Pro441Pro441Asp442Asp442Leu443Leu443Thr444Thr444Asp445Asp445Val446Val446Asn447Asn447Ser448Ser448Ile449Ile449Asp450Asp450450Lys451Lys451Trp452: Transmembrane domainTrp452: Transmembrane domainSer453: Transmembrane domainSer453: Transmembrane domainArg454: Transmembrane domainArg454: Transmembrane domainMet455: Transmembrane domainMet455: Transmembrane domainPhe456: Transmembrane domainPhe456: Transmembrane domainPhe457: Transmembrane domainPhe457: Transmembrane domainPro458: Transmembrane domainPro458: Transmembrane domainIle459: Transmembrane domainIle459: Transmembrane domainThr460: Transmembrane domainThr460: Transmembrane domain460Phe461: Transmembrane domainPhe461: Transmembrane domainSer462: Transmembrane domainSer462: Transmembrane domainLeu463: Transmembrane domainLeu463: Transmembrane domainPhe464: Transmembrane domainPhe464: Transmembrane domainAsn465: Transmembrane domainAsn465: Transmembrane domainVal466: Transmembrane domainVal466: Transmembrane domainVal467: Transmembrane domainVal467: Transmembrane domainTyr468: Transmembrane domainTyr468: Transmembrane domainTrp469: Transmembrane domainTrp469: Transmembrane domainLeu470: Transmembrane domainLeu470: Transmembrane domain470Tyr471: Transmembrane domainTyr471: Transmembrane domainTyr472: Transmembrane domainTyr472: Transmembrane domainVal473: Transmembrane domainVal473: Transmembrane domainHis474His474474Binding SiteActive siteTransmembrane domainPTMsvariantsdisulfide bondssignal peptideN-term: UniProtTMRs: UniProtGBRB1\_HUMANMWTVQNRESLGLLSFPVMITMVCCAHSTNEPSNMSYVKETVDRLLKGYDIRLRPDFGGPPVDVGMRIDVASIDMVSEVNMDYTLTMYFQQSWKDKRLSYSGIPLNLTLDNRVADQLWVPDTYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIESYGYTTDDIEFYWNGGEGAVTGVNKIELPQFSIVDYKMVSKKVEFTTGAYPRLSLSFRLKRNIGYFILQTYMPSTLITILSWVSFWINYDASAARVALGITTVLTMTTISTHLRETLPKIPYVKAIDIYLMGCFVFVFLALLEYAFVNYIFFGKGPQKKGASKQDQSANEKNKLEMNKVQVDAHGNILLSTLEIRNETSGSEVLTSVSDPKATMYSYDSASIQYRKPLSSREAYGRALDRHGVPSKGRIRRRASQLKVKIPDLTDVNSIDKWSRMFFPITFSLFNVVYWLYYVH Protein 3D structure Experimental structure from the Protein Data Bank, where one is available (Berman et al., Nucleic Acids Res. 2000). View 3D structure — PDB 9cxd (Electron Microscopy, chain C, 3.4 Å, 69% coverage) Small-molecule tractable with documented chemistry **GABRB1** is best approached as a small-molecule target (HIGH structural tractability — this modality-specific scorecard score, not the page's overall tractability figure) — 19 ChEMBL ligand(s) on record with max pChEMBL 6.9 (sub-µM affinity range or better). The structural case is clean: established chemistry exists, hit-to-lead expansion has a starting point. Modality choice is well-supported by the existing ligand corpus alongside whatever genetic / safety direction-of-effect indicates (inhibit / activate / degrade). C-STR-01.small\_molecule\_favourable · 3 evidence refs · 1 counterargument best modalitybest modality: small\_molecule (structural rating HIGH — modality-specific scorecard score, not the page-level overall tractability figure) small molecule chemistry19 ChEMBL ligand(s), max pChEMBL 6.90.19 antibody accessibilitymembrane, ECD fraction 0.460.46 Documented chemistry is thin Only 19 ChEMBL ligand(s) on record. The small-molecule case is real — affinity has been demonstrated — but the chemical-space exploration is limited. Hit-to-lead expansion from a small set of starting points carries more risk than from a rich ligand corpus. Budget medchem time accordingly. thin\_chemistry · weak ### 14Perturbation DEFAULT Perturbation score Expression-expert probability0.06 A model prior, not perturbation evidence on its own — the claim below requires a direction signal (DoE or MR) alongside this probability before treating it as concordance support, and none is on record for this pair. Disease expression context Modeled differential expression for this pair (no source study attached — see Panel 7) — the same measure Panel 7 shows. Not a LINCS perturbation signature and not a PCS score. DE directionUP GABRB1 log2fc+2.75 Source agreementN/A (not assessable — no sources) No perturbation data No Layer-1 expression-expert probability, no curated DoE direction, no MR-derived direction for **GABRB1** × **alzheimer's disease**. The perturbation axis is silent — neither supporting nor opposing the case. The platform's LINCS / DE viewers may still surface the underlying assay data for manual interpretation. C-PRT-01.absent ### 15Cell Lines DEFAULT Recommended cell lines — central nervous system lineages Disease-context lineage mapping + GABRB1 expression within lineage | Cell line | Lineage | GABRB1 expr | Dep. (Chronos) | Score | | --- | --- | --- | --- | --- | | U-118 MG | Central nervous system (Astrocytoma) | 26.6 | — | 7.5medium | | SF-295 | Central nervous system (Astrocytoma grade iv) | 13.1 | — | 7.5medium | | LN-235 | Central nervous system (Astrocytoma grade iv) | 11.7 | — | 7.4medium | | LN-340 | Central nervous system (Astrocytoma grade iv) | 10.1 | — | 7.3medium | | M059K | Central nervous system (Astrocytoma grade iv) | 7.9 | — | 7.3medium | | LN-18 | Central nervous system (Astrocytoma grade iv) | 3.5 | — | 7.2medium | Platform cell-line expression class (CCLE) · score td\_cell\_line\_relevance\_v2 · lineage mapping cl\_uberon\_to\_model\_lineage\_v1 · 984 candidate models · Per-model dependency is unavailable from the configured source. Lineage mapping evidence (10) - Central nervous system ← oligodendrocyte precursor cellCL:0002453da\_cell\_type\_proportions.cl - Central nervous system ← mature microglial cellCL:0002629da\_cell\_type\_proportions.cl - Central nervous system ← gabaergic neuronsCL:0000617da\_cell\_type\_proportions.cl - Central nervous system ← glutamatergic neuronCL:0000679da\_cell\_type\_proportions.cl - Central nervous system ← astrocytesCL:0000127da\_cell\_type\_proportions.cl - Central nervous system ← structure of entorhinal cortexUBERON:0002728da\_cell\_type\_proportions.uberon - Central nervous system ← mature astrocyteCL:0002627da\_cell\_type\_proportions.cl - Central nervous system ← prefrontal cortexUBERON:0000451da\_cell\_type\_proportions.uberon - Central nervous system ← neuronsCL:0000540da\_cell\_type\_proportions.cl - Central nervous system ← microgliaCL:0000129da\_cell\_type\_proportions.cl No DepMap dependency signal **GABRB1** is not depmap-essential (mean chronos 0.06, pLI 0.728). Cell-line work is still possible but won't be guided by loss-of-function dependency — use expression-filtered lines, pathway signatures, or pharmacological probes to design the in vitro venue. This is a cancer-cell-line dependency finding only — no cancer-cell dependency signal in the configured dataset. It does not establish tolerability in normal human tissue, development, immune function, or any specific organ, and does not override gnomAD pLI (shown above) or organ-toxicity evidence elsewhere on this page as a human-safety read. C-BIO-01.no\_dependency · 2 evidence refs depmap dependencyDepMap mean chronos = 0.060.04 pli essentialitygnomAD pLI = 0.7280.73 ## Read the methodology. Run a target through the platform. The whitepaper covers every pipeline, every reference, and the limitations explicitly. If you would like to see what the assessment view produces for one target in your therapeutic area, send us the gene and we will walk through it across the diseases where it scores. Download the methodology paper [Request a target walkthrough](mailto:information@euretos.com?subject=Disease%20Atlas%20-%20Target%20walkthrough) × ### Methodology & Validation, 2026 60 pages. Four pipelines. Every reference cited by PMID. Enter your details below and we will send the PDF directly. We do not sell or share your address. One follow-up at most. Disease Atlas | Euretos  ·  [information@euretos.com](mailto:information@euretos.com) ![](https://px.ads.linkedin.com/collect/?pid=3328428&conversionId=4680788&fmt=gif)