CausalSentinel

Protein Dossier — EMC1 (ER membrane protein complex subunit 1)

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
Forced expiratory volume in 1-second (FEV1) 0.0191 0.00641 0.00295 Wald ratio 1 trans NA
Non-cancer illness code self-reported: enlarged prostate 0.159 0.0542 0.0034 Wald ratio 1 trans NA
Fasting glucose 0.0309 0.0115 0.0073 Wald ratio 1 trans NA
Hearing difficulty or problems: Yes -0.0338 0.0132 0.0106 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.186 0.0813 0.0221 Wald ratio 1 trans NA
Birth length 0.0713 0.0317 0.0246 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms -0.157 0.071 0.0268 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0132 0.00608 0.0302 Wald ratio 1 trans NA
Ferritin -0.0629 0.0292 0.0313 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.102 0.0525 0.0525 Wald ratio 1 trans NA
Transferrin 0.0572 0.032 0.0735 Wald ratio 1 trans NA
Non-cancer illness code self-reported: migraine 0.0711 0.0399 0.075 Wald ratio 1 trans NA
…and 79 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

4 association rows across 4 traits (3 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
Aflatoxin B1 aldehyde reductase member 3 levels 5e-97 rs12095284 1 GCST90246404 no MR -> candidate analysis
Serum alkaline phosphatase levels 3e-13 rs144713581 1 GCST90018942 no MR -> candidate analysis
Resistance to COVID-19 infection (Exposed negative vs positi 3e-8 rs61764877 1 GCST90255358 no MR -> candidate analysis
Brain structure 1e-7 rs710865 1 GCST000597 no MR -> candidate analysis

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

Top diseases by Open Targets association (of 87 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
cerebellar atrophy, visual impairment, and psychomotor retardation; 0.892 established (curated) no MR -> candidate analysis
hereditary disease 0.817 established (curated) no MR -> candidate analysis
Retinal dystrophy 0.798 established (curated) no MR -> candidate analysis
Global developmental delay 0.669 established (curated) no MR -> candidate analysis
Cerebellar atrophy 0.669 established (curated) no MR -> candidate analysis
global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome 0.608 established (curated) no MR -> candidate analysis
autosomal recessive retinitis pigmentosa 0.547 established (curated) no MR -> candidate analysis
congenital anomaly of kidney and urinary tract 0.438 established (curated) no MR -> candidate analysis
Obesity 0.426 established (curated) no MR -> candidate analysis
retinitis pigmentosa 0.195 established (curated) no MR -> candidate analysis
microcephaly 0.182 established (curated) no MR -> candidate analysis

Of the 11 rows above, 11 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 0 known modulators (ER membrane protein complex subunit 1)
gnomAD constraint pLI=5.2e-28, LOEUF=0.942 — LoF-tolerant
GWAS Catalog 34 unique SNPs / 68 rows
ClinVar 1457 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance