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 |
|---|---|---|---|---|---|---|---|
| Body mass index (BMI) | -0.0112 | 0.00351 | 0.00136 | Wald ratio | 1 | cis | NA |
| Ovarian cancer | 0.0573 | 0.0189 | 0.00242 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: K20 Oesophagitis | 0.0931 | 0.0323 | 0.00398 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate | -0.141 | 0.0497 | 0.00461 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level | 0.328 | 0.122 | 0.00726 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: pneumothorax | 0.335 | 0.125 | 0.00745 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: R35 Polyuria | 0.122 | 0.0499 | 0.0143 | Wald ratio | 1 | cis | NA |
| Clear cell ovarian cancer | 0.143 | 0.0595 | 0.0159 | Wald ratio | 1 | cis | NA |
| Weight | -0.00676 | 0.0031 | 0.0293 | Wald ratio | 1 | cis | NA |
| Depressive symptoms | -0.0133 | 0.00626 | 0.0336 | Wald ratio | 1 | cis | NA |
| Lung cancer | 0.0512 | 0.0252 | 0.0417 | Wald ratio | 1 | cis | NA |
| Fractured bone site(s): Ankle | 0.0575 | 0.0283 | 0.0421 | Wald ratio | 1 | cis | NA |
| …and 69 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
220 association rows across 168 traits (202 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 |
|---|---|---|---|---|---|
| Semaphorin-4D levels | 5e-1164 | rs45464494 | 2 | GCST90249490 | no MR -> candidate analysis |
| Semaphorin-4D levels (SEMA4D.5737.61.3) | 2e-292 | rs140647145 | 2 | GCST90242748 | no MR -> candidate analysis |
| Blood protein levels | 2e-187 | rs45464494 | 1 | GCST006585 | no MR -> candidate analysis |
| CD84/SEMA4D protein level ratio | 2e-42 | rs11526468 | 1 | GCST90313917 | no MR -> candidate analysis |
| SEMA4D protein levels | 3e-41 | rs67607259 | 3 | GCST90470573 | no MR -> candidate analysis |
| Phospholipids to Total Lipids in Medium HDL percentage | 5e-28 | rs10908900 | 1 | GCST90501191 | no MR -> candidate analysis |
| Triglyceride levels | 9e-28 | rs3138490 | 6 | GCST90662893 | no MR -> candidate analysis |
| Vertex-wise sulcal depth | 9e-28 | rs3138493 | 1 | GCST90095129 | no MR -> candidate analysis |
| Gamma glutamyl transferase levels | 2e-21 | rs2183298 | 1 | GCST90662899 | no MR -> candidate analysis |
| Cholesterol to Total Lipids in Medium HDL percentage | 5e-20 | rs10908900 | 1 | GCST90501183 | no MR -> candidate analysis |
| Vertex-wise cortical surface area | 7e-20 | rs1007966 | 1 | GCST90095130 | no MR -> candidate analysis |
| Reticulocyte percentage (UKB data field 30240) | 8e-20 | rs11526468 | 1 | GCST90468101 | no MR -> candidate analysis |
| …and 156 more traits (see JSON) |
Top diseases by Open Targets association (of 640 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 |
|---|---|---|---|---|
| skin aging | 0.674 | — | common-variant locus | no MR -> candidate analysis |
| sclerosing cholangitis | 0.608 | — | established (curated) | no MR -> candidate analysis |
| placental abruption | 0.41 | — | common-variant locus | no MR -> candidate analysis |
| intelligence | 0.396 | — | common-variant locus | no MR -> candidate analysis |
| otosclerosis | 0.372 | — | common-variant locus | no MR -> candidate analysis |
Of the 5 rows above, 5 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 | 1 known modulators (Semaphorin-4D) |
| gnomAD constraint | pLI=1, LOEUF=0.42 — LoF-INTOLERANT |
| GWAS Catalog | 93 unique SNPs / 171 rows |
| ClinVar | 233 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 640 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 ‘SEMA4D’ and resolved to ‘Semaphorin-4D’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 233 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 168 traits by best p-value, aggregated from 220 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/Q92854 — 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/ENSG00000187764/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4630887/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SEMA4D — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SEMA4D — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SEMA4D%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SEMA4D — GWAS Catalog search API (live; release not exposed)