CausalSentinel

Protein Dossier — EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 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 vital capacity (FVC) -0.183 0.0104 2.89e-69 Wald ratio 1 cis NA
Height -0.265 0.0155 7.11e-66 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.141 0.011 8.87e-38 Wald ratio 1 cis NA
Weight -0.0942 0.0112 4.91e-17 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.474 0.0604 4.20e-15 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.903 0.207 1.32e-05 Wald ratio 1 cis NA
Hip osteoarthritis -0.616 0.142 1.45e-05 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0517 0.013 7.20e-05 Wald ratio 1 cis NA
Knee and hip osteoarthritis -0.417 0.112 2.04e-04 Wald ratio 1 cis NA
Potassium in urine -0.0397 0.0129 0.00212 Wald ratio 1 cis NA
Body mass index (BMI) 0.039 0.0127 0.00215 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -1.64 0.545 0.00255 Wald ratio 1 cis NA
…and 116 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

750 association rows across 188 traits (714 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
Height 4e-438 rs59985551 61 GCST90662911 MR: beta=-0.265, p=7.11e-66 (cis)
What is your height? (cm, inv-normal transformed) 1e-323 rs3791679 4 GCST90475368 no MR -> candidate analysis
Height (baseline) 2e-224 rs59985551 17 GCST90565843 no MR -> candidate analysis
Circulating EFEMP1 levels 3e-204 rs3791679 2 GCST90860478 no MR -> candidate analysis
EFEMP1 protein levels 4e-201 rs3791679 4 GCST90469078 no MR -> candidate analysis
height (mean, inv-normal transformed) 4e-165 rs3791679 3 GCST90479635 no MR -> candidate analysis
Body shape phenotype PC2 5e-165 rs59985551 2 GCST90832990 no MR -> candidate analysis
Height (maximum, inv-normal transformed) 4e-162 rs3791679 3 GCST90479634 no MR -> candidate analysis
height (minimum, inv-normal transformed) 1e-153 rs3791679 3 GCST90479636 no MR -> candidate analysis
Body size (confirmatory factor analysis Factor 21) 3e-117 rs59985551 1 GCST90309355 no MR -> candidate analysis
DLL1/EFEMP1 protein level ratio 2e-115 rs10199082 1 GCST90314494 no MR -> candidate analysis
CST3/EFEMP1 protein level ratio 1e-114 rs6755214 1 GCST90314292 no MR -> candidate analysis
…and 176 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 1783 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
Inguinal hernia 0.842 established (curated) MR: beta=-1.64, p=0.00255 (cis)
open-angle glaucoma 0.737 established (curated) no MR -> candidate analysis
Doyne honeycomb retinal dystrophy 0.676 established (curated) no MR -> candidate analysis
cutis laxa, autosomal recessive, type 1d 0.787 established (curated) no MR -> candidate analysis
Familial drusen 0.676 established (curated) no MR -> candidate analysis
myopia 0.735 established (curated) no MR -> candidate analysis
Hernia of the abdominal wall 0.717 0.152 multi-layer: burden+GWAS (allelic-series candidate) no MR -> candidate analysis
Abnormality of the skeletal system 0.861 common-variant locus no MR -> candidate analysis
Hernia 0.686 0.152 multi-layer: burden+GWAS (allelic-series candidate) MR: beta=-1.64, p=0.00255 (cis)
diverticular disease 0.842 common-variant locus MR: beta=-0.385, p=0.00419 (cis)
ventral hernia 0.842 common-variant locus MR: beta=-0.449, p=0.189 (cis)
diaphragmatic hernia 0.842 common-variant locus MR: beta=0.165, p=0.0584 (cis)
carpal tunnel syndrome 0.791 common-variant locus no MR -> candidate analysis
Umbilical hernia 0.772 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.764 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 10 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 2 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, LOEUF=0.406 — LoF-INTOLERANT
GWAS Catalog 308 unique SNPs / 747 rows
ClinVar 440 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance