CausalSentinel

Protein Dossier — FAM174A (Membrane protein FAM174A)

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
Squamous cell lung cancer 0.129 0.0513 0.0118 Wald ratio 1 trans NA
Diagnoses - main ICD10: L03 Cellulitis -0.16 0.0645 0.0132 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast -0.0981 0.0425 0.0209 Wald ratio 1 trans NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0547 0.0242 0.0236 Wald ratio 1 trans NA
Serum cystatin C (eGFRcys) 0.00866 0.00399 0.0299 Wald ratio 1 trans NA
Lung adenocarcinoma 0.108 0.0515 0.0364 Wald ratio 1 trans NA
Lung cancer 0.0688 0.0352 0.0508 Wald ratio 1 trans NA
Non-cancer illness code self-reported: high cholesterol -0.0264 0.0137 0.0538 Wald ratio 1 trans NA
Chronic kidney disease -0.0593 0.0308 0.0541 Wald ratio 1 trans NA
Sodium in urine 0.00932 0.00484 0.0543 Wald ratio 1 trans NA
Forearm bone mineral density -0.0594 0.0318 0.0619 Wald ratio 1 trans NA
Myocardial infarction 0.0417 0.0228 0.0677 Wald ratio 1 trans NA
…and 77 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

33 association rows across 22 traits (26 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
Hematological traits (multi-trait analysis) 7e-50 rs62387563 2 GCST90838669 no MR -> candidate analysis
Bone mineral density mean 1e-42 rs72776654 1 GCST90321120 no MR -> candidate analysis
Estimated bone mineral density 5e-19 rs34187381 1 GCST90726625 no MR -> candidate analysis
Heel bone mineral density 1e-17 rs10515269 3 GCST006979 no MR -> candidate analysis
Smoking initiation 3e-16 rs766693 5 GCST90243985 no MR -> candidate analysis
White blood cell count 1e-14 rs62387565 2 GCST90002374 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 4e-14 rs32282; rs10491363; rs282072 2 GCST008413 no MR -> candidate analysis
Neutrophil count 1e-13 rs1445171 2 GCST90002351 no MR -> candidate analysis
Circulating CR2 levels 9e-13 rs1394622 1 GCST90860456 no MR -> candidate analysis
CR2 protein levels 2e-12 rs1394622 1 GCST90468852 no MR -> candidate analysis
Educational attainment 6e-12 rs468216 1 GCST90105038 no MR -> candidate analysis
Type 2 diabetes 1e-11 rs112725069 1 GCST90444202 no MR -> candidate analysis
…and 10 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 32 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
neuroendocrine neoplasm 0.348 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.295 common-variant locus no MR -> candidate analysis
Abdominal pain 0.245 common-variant locus MR: beta=0.0412, p=0.0708 (trans)
disorder of ear 0.073 common-variant locus no MR -> candidate analysis
aortic aneurysm 0.043 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.038 common-variant locus no MR -> candidate analysis
liver disorder 0.037 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 6 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=1.5e-05, LOEUF=1.53 — LoF-tolerant
GWAS Catalog 22 unique SNPs / 44 rows
ClinVar 63 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance