CausalSentinel

Protein Dossier — OLFM2 (Noelin-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
Fractured bone site(s): Other bones 0.0329 0.0158 0.0376 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.0533 0.0277 0.0541 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina -0.0406 0.022 0.0644 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.00677 0.00385 0.0789 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.143 0.0822 0.0809 Wald ratio 1 cis NA
Bulimia nervosa -0.0253 0.0149 0.0891 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.0919 0.0547 0.0932 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment 0.0977 0.0596 0.101 Wald ratio 1 cis NA
Eczema 0.0479 0.0293 0.102 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate -0.0521 0.0339 0.124 Wald ratio 1 cis NA
Putamen volume -16 10.4 0.124 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) 0.0611 0.0408 0.134 Wald ratio 1 cis NA
…and 50 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

28 association rows across 23 traits (25 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
Noelin-2 levels 8e-1001 rs55732232 2 GCST90248703 no MR -> candidate analysis
Serum levels of protein OLFM2 1e-293 rs11669788 1 GCST90090108 no MR -> candidate analysis
Blood protein levels 6e-157 rs56243392 1 GCST006585 no MR -> candidate analysis
Menarche (age at onset) 4e-31 rs8112411 4 GCST007078 no MR -> candidate analysis
Protein S100-A7 protein levels (SomaScan ID:8295-16) 6e-24 rs56243392 1 GCST90439856 no MR -> candidate analysis
Heterogeneous nuclear ribonucleoprotein R protein levels (So 1e-23 rs56243392 1 GCST90437054 no MR -> candidate analysis
Impedance of arm left (UKB data field 23110) 2e-20 rs10413248 1 GCST90468171 no MR -> candidate analysis
Impedance of arm right (UKB data field 23109) 2e-19 rs10413248 1 GCST90468172 no MR -> candidate analysis
Noelin-2 level in Chronic kidney disease with hypertension a 9e-19 rs56243392 1 GCST90238869 no MR -> candidate analysis
Noelin-2 level in Chronic kidney disease with hypertension a 1e-18 rs56243392 1 GCST90235246 no MR -> candidate analysis
Appendicular lean mass 3e-16 rs12979274 1 GCST90000025 no MR -> candidate analysis
GLIPR1 protein levels 1e-13 rs117167271 1 GCST90469357 no MR -> candidate analysis
…and 11 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 1005 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
Abnormality of the skeletal system 0.464 common-variant locus no MR -> candidate analysis
vertebral column disorder 0.323 common-variant locus no MR -> candidate analysis
liver disorder 0.234 common-variant locus no MR -> candidate analysis
esophageal disorder 0.234 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.228 common-variant locus no MR -> candidate analysis
immune system disorder 0.139 common-variant locus no MR -> candidate analysis
osteoarthritis 0.097 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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=0.037, LOEUF=0.661 — LoF-tolerant
GWAS Catalog 47 unique SNPs / 94 rows
ClinVar 93 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance