MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Coronary heart disease | 0.103 | 0.0347 | 0.00303 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: high cholesterol | 0.0632 | 0.0229 | 0.00567 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt | 0.209 | 0.0816 | 0.0104 | Wald ratio | 1 | cis | NA |
| Heel bone mineral density (BMD) T-score automated | -0.029 | 0.0117 | 0.0128 | Wald ratio | 1 | cis | NA |
| Hearing difficulty or problems: Yes | -0.0385 | 0.0161 | 0.0171 | Wald ratio | 1 | cis | NA |
| Myocardial infarction | 0.0892 | 0.0386 | 0.0208 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) | 0.125 | 0.0565 | 0.0265 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | -0.0164 | 0.00779 | 0.0349 | Wald ratio | 1 | cis | NA |
| Caudate volume | 40.5 | 19.4 | 0.0365 | Wald ratio | 1 | cis | NA |
| Ferritin | 0.0786 | 0.0376 | 0.0367 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: N81 Female genital prolapse | -0.192 | 0.0921 | 0.0367 | Wald ratio | 1 | cis | NA |
| Chronic kidney disease | 0.125 | 0.0612 | 0.0404 | Wald ratio | 1 | cis | NA |
| …and 113 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
48 association rows across 38 traits (42 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait | best p | lead SNP | n assoc | study | MR status |
|---|---|---|---|---|---|
| mean platelet volume (MPV, mean, inv-norm transformed) | 2e-68 | rs13053850 | 2 | GCST90475520 | no MR -> candidate analysis |
| Homer protein homolog 1 levels | 1e-66 | rs2301584 | 1 | GCST90247928 | no MR -> candidate analysis |
| SH3 and multiple ankyrin repeat domains protein 3 levels | 2e-64 | rs5770821 | 1 | GCST90249532 | no MR -> candidate analysis |
| mean platelet volume (MPV, maximum, inv-norm transformed) | 6e-57 | rs13053850 | 2 | GCST90475517 | no MR -> candidate analysis |
| Mean platelet volume | 2e-48 | rs13053850 | 2 | GCST90002346 | MR: beta=0.00612, p=0.182 (cis) |
| Homer protein homolog 2 levels | 3e-39 | rs62242890 | 1 | GCST90247929 | no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) | 1e-36 | rs13053850 | 1 | GCST90838669 | no MR -> candidate analysis |
| PLXNB2 protein levels | 1e-33 | rs9628240 | 1 | GCST90470266 | no MR -> candidate analysis |
| mean platelet volume (MPV, minimum, inv-norm transformed) | 5e-31 | rs9616908 | 1 | GCST90479709 | no MR -> candidate analysis |
| Serum levels of protein CHKB | 6e-22 | rs141909966 | 1 | GCST90089813 | no MR -> candidate analysis |
| Educational attainment (MTAG) | 2e-20 | rs9616947 | 1 | GCST006571 | no MR -> candidate analysis |
| Educational attainment | 2e-20 | rs1024374 | 1 | GCST90105038 | no MR -> candidate analysis |
| …and 26 more traits (see JSON) |
Top diseases by Open Targets association (of 1996 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.
| Disease | genetic assoc. | burden (ExWAS) | causal status | MR status |
|---|---|---|---|---|
| Phelan-McDermid syndrome | 0.905 | — | established (curated) | no MR -> candidate analysis |
| Monosomy 22q13 | 0.942 | — | established (curated) | no MR -> candidate analysis |
| schizophrenia 15 | 0.819 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.901 | — | established (curated) | no MR -> candidate analysis |
| Intellectual disability | 0.882 | — | established (curated) | no MR -> candidate analysis |
| autism spectrum disorder | 0.654 | 0.152 | established (curated) | no MR -> candidate analysis |
| Neurodevelopmental delay | 0.699 | — | established (curated) | no MR -> candidate analysis |
| mathematical ability | 0.582 | — | common-variant locus | no MR -> candidate analysis |
| neurodevelopmental disorder | 0.559 | — | established (curated) | no MR -> candidate analysis |
| schizophrenia | 0.53 | — | common-variant locus | MR: beta=0.074, p=0.0606 (cis) |
| psychotic disorder | 0.559 | — | established (curated) | no MR -> candidate analysis |
| Neurodevelopmental abnormality | 0.559 | — | established (curated) | no MR -> candidate analysis |
| Autistic behavior | 0.559 | — | established (curated) | no MR -> candidate analysis |
| Moderate global developmental delay | 0.559 | — | established (curated) | no MR -> candidate analysis |
| Mutism | 0.559 | — | established (curated) | no MR -> candidate analysis |
Of the 15 rows above, 14 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
| Layer | Result |
|---|---|
| ChEMBL druggability | 0 known modulators (SH3 and multiple ankyrin repeat domains protein 3) |
| gnomAD constraint | pLI=1, LOEUF=0.365 — LoF-INTOLERANT |
| GWAS Catalog | 87 unique SNPs / 174 rows |
| ClinVar | 1485 records; 7 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 1996 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘SHANK3’ and resolved to ‘SH3 and multiple ankyrin repeat domains protein 3’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 1485 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 38 traits by best p-value, aggregated from 48 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/Q9BYB0 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000251322/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5465313/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SHANK3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SHANK3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SHANK3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SHANK3 — GWAS Catalog search API (live; release not exposed)