CausalSentinel

Protein Dossier — GRAMD1C (Protein Aster-C)

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): Ankle -0.154 0.041 1.74e-04 Wald ratio 1 cis NA
Body mass index (BMI) 0.0122 0.00411 0.00294 Wald ratio 1 cis NA
Weight 0.0107 0.00363 0.00305 Wald ratio 1 cis NA
Ovarian cancer -0.0614 0.0234 0.00879 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.0701 0.03 0.0193 Wald ratio 1 cis NA
Years of schooling -0.0145 0.00645 0.0244 Wald ratio 1 cis NA
HbA1C 0.0134 0.00597 0.0249 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0343 0.0154 0.0259 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years -0.0292 0.0132 0.0266 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.055 0.0255 0.0311 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting -0.166 0.0777 0.0329 Wald ratio 1 cis NA
Happiness 0.0106 0.0051 0.0367 Wald ratio 1 cis NA
…and 81 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

21 association rows across 11 traits (15 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
GRAM domain-containing protein 1C levels 3e-338 rs1872823 4 GCST90247815 no MR -> candidate analysis
Serum levels of protein GRAMD1C 1e-262 rs61634901 4 GCST90090335 no MR -> candidate analysis
GRAM domain-containing protein 1C levels (GRAMD1C.8842.16.3) 3e-148 rs61077924 4 GCST90241314 no MR -> candidate analysis
Blood protein levels 4e-133 rs4422272 1 GCST006585 no MR -> candidate analysis
CD200R1 protein levels 5e-45 rs564438696 2 GCST90468605 no MR -> candidate analysis
3-hydroxypropylmercapturic acid levels in smokers 8e-8 rs114780919 1 GCST002956 no MR -> candidate analysis
Urinary uromodulin levels (raw) 1e-6 rs139248026 1 GCST90103502 no MR -> candidate analysis
Lateral ventricle temporal horn volume 3e-6 rs73230239 1 GCST009218 no MR -> candidate analysis
Stuttering 5e-6 rs145711937 1 GCST90707223 no MR -> candidate analysis
5-HETrE levels in elite athletes 7e-6 rs6438172 1 GCST90133836 no MR -> candidate analysis
Prospective and Retrospective Memory Questionnaire (PRMQ) Re 7e-6 rs6798319 1 GCST90448158 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 337 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
gastritis 0.393 common-variant locus MR: beta=-0.0187, p=0.491 (cis)
myocardial ischemia 0.324 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 1 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 (Protein Aster-C)
gnomAD constraint pLI=8.7e-28, LOEUF=1.09 — LoF-tolerant
GWAS Catalog 23 unique SNPs / 46 rows
ClinVar 134 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance