CausalSentinel

Protein Dossier — ERAP2 (Endoplasmic reticulum aminopeptidase 2)

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
Crohn’s disease 0.0872 0.0119 1.97e-13 Wald ratio 1 cis 0.466
Inflammatory bowel disease 0.0701 0.0098 8.75e-13 Wald ratio 1 cis 0.645
Diastolic blood pressure automated reading 0.0133 0.00235 1.56e-08 Wald ratio 1 cis 0.952
Ulcerative colitis 0.0528 0.0123 1.70e-05 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.00826 0.00235 4.43e-04 Wald ratio 1 cis NA
IgA nephropathy 0.244 0.0751 0.00119 Wald ratio 1 cis NA
Fasting glucose -0.0095 0.00295 0.00126 Wald ratio 1 cis NA
Juvenile idiopathic arthritis 0.16 0.0512 0.0018 Wald ratio 1 cis NA
Multiple sclerosis -0.0464 0.0162 0.00413 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.00551 0.00199 0.00558 Wald ratio 1 cis NA
Fractured bone site(s): Ankle 0.0511 0.0186 0.00608 Wald ratio 1 cis NA
Schizophrenia -0.0265 0.0102 0.00913 Wald ratio 1 cis NA
…and 108 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

150 association rows across 73 traits (134 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
Endoplasmic reticulum aminopeptidase 2 levels 5e-4961 rs2927608 3 GCST90247487 no MR -> candidate analysis
Endoplasmic reticulum aminopeptidase 2 levels (ERAP2.8960.3. 7e-858 rs2927608 4 GCST90241043 no MR -> candidate analysis
ERAP2 protein levels 1e-305 rs2910686 10 GCST90453311 no MR -> candidate analysis
HLA E protein levels 2e-232 rs2927608 1 GCST90469459 no MR -> candidate analysis
Endoplasmic reticulum aminopeptidase 2 level in Chronic kidn 7e-161 rs2927608 1 GCST90239121 no MR -> candidate analysis
Endoplasmic reticulum aminopeptidase 1 levels (ERAP1.4964.67 5e-137 rs73774722 1 GCST90241042 no MR -> candidate analysis
LAMB1 protein levels 2e-129 rs2927608 1 GCST90469732 no MR -> candidate analysis
ESAM/TGFB1 protein level ratio 1e-64 rs2549794 1 GCST90314718 no MR -> candidate analysis
ERAP1 protein levels 1e-55 rs35136 5 GCST90453391 no MR -> candidate analysis
Circulating TGFB1 levels (id: OID00480_OID20621) 8e-52 rs251343 1 GCST90859840 no MR -> candidate analysis
TGFB1 protein levels 4e-49 rs3985004 1 GCST90470843 no MR -> candidate analysis
Circulating TGFB1 levels (id: OID00785_OID20621) 1e-44 rs251343 1 GCST90860117 no MR -> candidate analysis
…and 61 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 218 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
inflammatory bowel disease 0.619 common-variant locus MR: beta=0.0701, p=8.75e-13 (cis)
hypertensive disorder 0.595 common-variant locus no MR -> candidate analysis
Crohn disease 0.577 common-variant locus no MR -> candidate analysis
venous thromboembolism 0.515 common-variant locus no MR -> candidate analysis
juvenile idiopathic arthritis 0.445 common-variant locus MR: beta=0.16, p=0.0018 (cis)
psoriatic arthritis 0.445 common-variant locus no MR -> candidate analysis
psoriasis 0.436 common-variant locus MR: beta=-0.0296, p=0.183 (cis)
attention deficit-hyperactivity disorder 0.425 common-variant locus no MR -> candidate analysis
substance abuse 0.425 common-variant locus no MR -> candidate analysis
lichen planus 0.417 common-variant locus no MR -> candidate analysis
birdshot chorioretinopathy 0.373 common-variant locus no MR -> candidate analysis
pulmonary vascular congestion 0.385 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.379 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.375 common-variant locus no MR -> candidate analysis
skin neoplasm 0.283 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 12 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 (Endoplasmic reticulum aminopeptidase 2)
gnomAD constraint pLI=6.6e-43, LOEUF=1.24 — LoF-tolerant
GWAS Catalog 133 unique SNPs / 331 rows
ClinVar 181 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance