CausalSentinel

Protein Dossier — SEMA5A (Semaphorin-5A)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome beta se p method nSNP cis/trans coloc
Systolic blood pressure automated reading -0.0102 0.00288 4.08e-04 Wald ratio 1 cis NA
Birth weight 0.0133 0.00454 0.00347 Wald ratio 1 cis NA
Happiness 0.00956 0.00347 0.00584 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.0686 0.0255 0.00715 Wald ratio 1 cis NA
Femoral neck bone mineral density -0.0215 0.00909 0.0183 Wald ratio 1 cis NA
Endometrioid ovarian cancer -0.082 0.0379 0.0305 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.105 0.0485 0.0306 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypopituitarism 0.259 0.12 0.0312 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0263 0.0122 0.0313 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0199 0.00925 0.0314 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma 0.0589 0.0278 0.0339 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.0748 0.0356 0.0357 Wald ratio 1 cis NA
…and 63 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

59 association rows across 47 traits (30 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-5A levels 1e-72 rs368861373 9 GCST90161309 no MR -> candidate analysis
Semaphorin-5B levels 1e-36 rs17262778 1 GCST90423774 no MR -> candidate analysis
Serum levels of protein SEMA5A 3e-35 rs3797975 1 GCST90087396 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 2e-16 rs10062083; rs922548; rs17238371; rs13359124; rs12519207; rs6876019; rs6555593; rs983856; rs6863413; rs16882096; rs12189232; rs984425; rs899575; rs899576; rs886511 2 GCST008413 no MR -> candidate analysis
Vertex-wise sulcal depth 3e-16 rs788321 1 GCST90095129 no MR -> candidate analysis
V-type proton ATPase subunit C 2 protein levels (SomaScan ID 7e-14 rs72729191 1 GCST90440048 no MR -> candidate analysis
GLIPR1 protein levels 2e-13 rs182334129 1 GCST90469357 no MR -> candidate analysis
Coronary artery disease 4e-13 rs112941079 1 GCST005195 no MR -> candidate analysis
Pyogenic arthritis (PheCode 711.1) 4e-12 rs530847695 1 GCST90480495 no MR -> candidate analysis
Cortical surface area 6e-12 rs788321 1 GCST90091060 no MR -> candidate analysis
Vertex-wise cortical surface area 6e-12 rs788321 1 GCST90095130 no MR -> candidate analysis
Arthropathy associated with infections (PheCode 711) 3e-11 rs530847695 1 GCST90480496 no MR -> candidate analysis
…and 35 more traits (see JSON)          

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 202 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
coronary artery disorder 0.821 common-variant locus no MR -> candidate analysis
hair color 0.672 common-variant locus no MR -> candidate analysis
heart disorder 0.655 common-variant locus no MR -> candidate analysis
myocardial ischemia 0.624 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.61 common-variant locus no MR -> candidate analysis
alcohol drinking 0.546 common-variant locus no MR -> candidate analysis
subarachnoid hemorrhage 0.504 common-variant locus no MR -> candidate analysis
Nasal polyposis 0.484 common-variant locus no MR -> candidate analysis
sialadenitis 0.479 common-variant locus no MR -> candidate analysis
gestational diabetes 0.445 common-variant locus no MR -> candidate analysis
central nervous system infectious disorder 0.436 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.431 common-variant locus no MR -> candidate analysis
breast disorder 0.431 common-variant locus no MR -> candidate analysis
breast benign neoplasm 0.427 common-variant locus no MR -> candidate analysis
pneumonia 0.382 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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.

5. Downstream annotation (druggability & safety preview)

Layer Result
ChEMBL druggability not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=0.37, LOEUF=0.508 — LoF-tolerant
GWAS Catalog 81 unique SNPs / 162 rows
ClinVar 382 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance