CausalSentinel

Protein Dossier — HNRNPC (Heterogeneous nuclear ribonucleoproteins C1/C2)

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
Height 0.0326 0.0111 0.00338 Wald ratio 1 trans NA
Neo-agreeableness 0.647 0.239 0.00673 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pneumothorax 0.572 0.249 0.0214 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated 0.0248 0.0108 0.0221 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.212 0.099 0.0322 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.192 0.101 0.0585 Wald ratio 1 trans NA
Fractured bone site(s): Wrist 0.0962 0.0544 0.0768 Wald ratio 1 trans NA
Non-cancer illness code self-reported: muscle or soft tissue injuries 0.15 0.0857 0.0791 Wald ratio 1 trans NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.113 0.0657 0.0853 Wald ratio 1 trans NA
Haemoglobin concentration 0.0443 0.0261 0.0894 Wald ratio 1 trans NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions -0.288 0.171 0.0925 Wald ratio 1 trans NA
Packed cell volume 0.149 0.09 0.0984 Wald ratio 1 trans NA
…and 84 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

9 association rows across 7 traits (7 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 2e-48 rs8016099 2 GCST90245848 MR: beta=0.0326, p=0.00338 (trans)
C-reactive protein levels 2e-10 rs11156891 2 GCST90029070 no MR -> candidate analysis
C-reactive protein levels (MTAG) 1e-9 rs12589290 1 GCST90179146 no MR -> candidate analysis
Height (baseline) 4e-9 rs59988950 1 GCST90565843 no MR -> candidate analysis
Albumin levels 9e-9 rs35141059 1 GCST90662901 no MR -> candidate analysis
Bipolar disorder 2e-6 rs17197037 1 GCST001135 MR: beta=0.185, p=0.183 (trans)
Trauma exposure 7e-6 rs111571004 1 GCST009982 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 432 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
intellectual developmental disorder, autosomal dominant 74 0.718 established (curated) no MR -> candidate analysis
complex neurodevelopmental disorder 0.608 established (curated) no MR -> candidate analysis
hereditary disease 0.308 established (curated) no MR -> candidate analysis

Of the 3 rows above, 3 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 (Heterogeneous nuclear ribonucleoproteins C1/C2)
gnomAD constraint pLI=1, LOEUF=0.233 — LoF-INTOLERANT
GWAS Catalog 32 unique SNPs / 63 rows
ClinVar 121 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance