CausalSentinel

Protein Dossier — EMC4 (ER membrane protein complex subunit 4)

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 -0.143 0.0467 0.0022 Wald ratio 1 trans NA
2hr glucose -0.121 0.0455 0.00766 Wald ratio 1 trans NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.0589 0.0244 0.0157 Wald ratio 1 trans NA
Fractured bone site(s): Ankle -0.0929 0.0397 0.0192 Wald ratio 1 trans NA
Non-cancer illness code self-reported: retinal detachment 0.146 0.0639 0.0226 Wald ratio 1 trans NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.329 0.148 0.0264 Wald ratio 1 trans NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis -0.155 0.0727 0.0331 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bone disorder 0.16 0.0774 0.0391 Wald ratio 1 trans NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.0954 0.0473 0.0435 Wald ratio 1 trans NA
Fractured or broken bones in last 5 years -0.0268 0.0135 0.0477 Wald ratio 1 trans NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.0574 0.0304 0.0587 Wald ratio 1 trans NA
HDL cholesterol 0.0185 0.00986 0.0605 Wald ratio 1 trans NA
…and 91 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

1 association rows across 1 traits (1 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) 5e-9 rs57626952 1 GCST90838669 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 35 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
agenesis of the corpus callosum with peripheral neuropathy 0.265 established (curated) no MR -> candidate analysis

Of the 1 rows above, 1 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=0.59, LOEUF=0.65 — LoF-tolerant
GWAS Catalog 10 unique SNPs / 20 rows
ClinVar 54 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance