CausalSentinel

Protein Dossier — NCAM2 (Neural cell adhesion molecule 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 or broken bones in last 5 years -0.0712 0.0243 0.00339 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.0955 0.0355 0.0072 Wald ratio 1 cis NA
Microalbuminuria 0.157 0.0649 0.0157 Wald ratio 1 cis NA
Fractured bone site(s): Wrist -0.14 0.0598 0.0191 Wald ratio 1 cis NA
Age at menarche -0.0405 0.0176 0.021 Wald ratio 1 cis NA
Height -0.0211 0.00919 0.0218 Wald ratio 1 cis NA
Bulimia nervosa 0.0486 0.0216 0.0244 Wald ratio 1 cis NA
Endometrioid ovarian cancer -0.17 0.0866 0.0492 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0143 0.00743 0.0536 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.104 0.0568 0.0676 Wald ratio 1 cis NA
Urinary albumin-to-creatinine ratio 0.0351 0.0203 0.083 Wald ratio 1 cis NA
Fractured bone site(s): Other bones -0.0578 0.0335 0.0843 Wald ratio 1 cis NA
…and 90 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

94 association rows across 48 traits (71 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
ENG/NCAM2 protein level ratio 2e-499 rs9981968 1 GCST90314647 no MR -> candidate analysis
Bone mineral density mean 1e-300 rs75886385 2 GCST90321120 no MR -> candidate analysis
NCAM2 protein levels 4e-127 rs236061 33 GCST90470004 no MR -> candidate analysis
Serum levels of protein NCAM2 9e-64 rs2826851 3 GCST90089466 no MR -> candidate analysis
Cerebrospinal fluid protein NCAM2 levels 2e-56 rs232451 1 GCST90944831 no MR -> candidate analysis
Blood protein levels 2e-42 rs2826851 1 GCST006585 no MR -> candidate analysis
Neural cell adhesion molecule 2 levels 6e-40 rs233757 4 GCST90248612 no MR -> candidate analysis
Neural cell adhesion molecule 2 levels (NCAM2.6507.16.3) 5e-36 rs34963977 2 GCST90242055 no MR -> candidate analysis
Smoking initiation 1e-20 rs34058918 2 GCST90243985 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Large HDL ratio 9e-18 rs74728378 1 GCST90827800 no MR -> candidate analysis
Severe COVID-19 infection 3e-15 rs232479 3 GCST90255357 no MR -> candidate analysis
GLIPR1 protein levels 2e-14 rs554536595 1 GCST90469357 no MR -> candidate analysis
…and 36 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 205 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
smoking initiation 0.686 common-variant locus no MR -> candidate analysis
parasitic infectious disease 0.523 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.516 common-variant locus no MR -> candidate analysis
substance abuse 0.516 common-variant locus no MR -> candidate analysis
venous thromboembolism 0.5 common-variant locus no MR -> candidate analysis
infectious meningitis 0.492 common-variant locus no MR -> candidate analysis
Abnormality of the integument 0.485 common-variant locus no MR -> candidate analysis
hemiplegia 0.485 common-variant locus no MR -> candidate analysis
response to stimulus 0.482 common-variant locus no MR -> candidate analysis
sign or symptom 0.472 common-variant locus no MR -> candidate analysis
device complication 0.455 common-variant locus no MR -> candidate analysis
schizophrenia 0.432 common-variant locus MR: beta=-0.0473, p=0.152 (cis)
frozen shoulder 0.418 common-variant locus no MR -> candidate analysis
COVID-19 0.409 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.409 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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=1, LOEUF=0.415 — LoF-INTOLERANT
GWAS Catalog 89 unique SNPs / 172 rows
ClinVar 234 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance