CausalSentinel

Protein Dossier — NFASC (Neurofascin)

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
Diagnoses - main ICD10: I84 Haemorrhoids 0.0917 0.0263 4.78e-04 Inverse variance weighted 2 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.0917 0.0263 4.78e-04 Inverse variance weighted 2 trans NA
Neo-conscientiousness 0.571 0.165 5.39e-04 Wald ratio 1 cis NA
Neuroticism -0.0219 0.00691 0.00155 Inverse variance weighted 2 cis NA
Neuroticism -0.0219 0.00691 0.00155 Inverse variance weighted 2 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0562 0.0204 0.00595 Inverse variance weighted 2 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0562 0.0204 0.00595 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: enlarged prostate 0.0893 0.035 0.0108 Inverse variance weighted 2 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.0893 0.035 0.0108 Inverse variance weighted 2 trans NA
Hippocampus volume -23 9.19 0.0121 Wald ratio 1 cis NA
Ischemic stroke -0.0832 0.034 0.0146 Wald ratio 1 cis NA
Childhood intelligence 0.0579 0.026 0.0261 Wald ratio 1 cis NA
…and 157 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

89 association rows across 52 traits (64 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
Circulating CNTN2 levels 6e-1074 rs12032559 5 GCST90860318 no MR -> candidate analysis
NFASC/PLXNB2 protein level ratio 9e-821 rs6657372 1 GCST90315537 no MR -> candidate analysis
Neurofascin levels 8e-274 rs6667532 1 GCST90248666 no MR -> candidate analysis
NFASC protein levels 3e-125 rs11806216 7 GCST90470031 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 3e-110 rs10657459 3 GCST90468087 no MR -> candidate analysis
CNTN2 protein levels 6e-106 rs72753439 9 GCST90468804 no MR -> candidate analysis
Neurofascin levels (NFASC.7179.69.3) 4e-100 rs6667532 2 GCST90242075 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 4e-59 rs11240324 3 GCST90838671 no MR -> candidate analysis
Serum levels of protein NFASC 2e-58 rs6663324 2 GCST90089710 no MR -> candidate analysis
Mean platelet volume 3e-58 rs11240325 2 GCST90002395 MR: beta=-0.00427, p=0.0389 (cis)
Blood protein levels 8e-37 rs6663324 2 GCST006585 no MR -> candidate analysis
Platelet count (UKB data field 30080) 1e-24 rs11240325 2 GCST90468095 no MR -> candidate analysis
…and 40 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 716 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
neurodevelopmental disorder with central and peripheral motor dysfunction 0.851 established (curated) no MR -> candidate analysis
hereditary disease 0.684 established (curated) no MR -> candidate analysis
risk-taking behaviour 0.586 common-variant locus no MR -> candidate analysis
hair color 0.533 common-variant locus no MR -> candidate analysis
dermatophytosis 0.501 common-variant locus no MR -> candidate analysis
neoplasm 0.396 common-variant locus MR: beta=-0.0684, p=0.116 (cis)
circadian rhythm 0.385 common-variant locus no MR -> candidate analysis
spondylolisthesis 0.327 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.327 common-variant locus no MR -> candidate analysis
neuromuscular disease 0.243 established (curated) no MR -> candidate analysis

Of the 10 rows above, 9 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=0.376 — LoF-INTOLERANT
GWAS Catalog 128 unique SNPs / 288 rows
ClinVar 371 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance