CausalSentinel

Protein Dossier — CCDC126 (Coiled-coil domain-containing protein 126)

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: R07 Pain in throat and chest 0.124 0.0346 3.33e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.285 0.0908 0.00172 Wald ratio 1 cis NA
Schizophrenia -0.113 0.0393 0.00387 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0206 0.00721 0.0043 Wald ratio 1 cis NA
Rheumatoid arthritis -0.177 0.0622 0.00432 Wald ratio 1 cis NA
Neuroticism -0.0291 0.0109 0.00766 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0196 0.0076 0.0101 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.125 0.0551 0.0231 Wald ratio 1 cis NA
Cancer code self-reported: malignant melanoma -0.287 0.136 0.0346 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.16 0.0761 0.0351 Wald ratio 1 cis NA
Hirschsprung’s disease -0.936 0.497 0.0594 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.578 0.315 0.0671 Wald ratio 1 cis NA
…and 99 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

15 association rows across 15 traits (14 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
Coiled-coil domain-containing protein 126 levels 1e-140 rs35121828 1 GCST90246891 no MR -> candidate analysis
Serum levels of protein CCDC126 1e-37 rs227937 1 GCST90089389 no MR -> candidate analysis
Coiled-coil domain-containing protein 126 levels (CCDC126.63 7e-29 rs227934 1 GCST90240731 no MR -> candidate analysis
Height (baseline) 5e-23 rs34576444 1 GCST90565843 no MR -> candidate analysis
Blood protein levels 4e-19 rs143669862 1 GCST006585 no MR -> candidate analysis
CR2 protein levels 2e-16 rs145235515 1 GCST90468852 no MR -> candidate analysis
Circulating CR2 levels 3e-16 rs13231199 1 GCST90860456 no MR -> candidate analysis
Alkaline phosphatase (UKB data field 30610) 5e-16 rs67998529 1 GCST90468060 no MR -> candidate analysis
FEV1 5e-15 rs12700451 1 GCST90270081 MR: beta=-0.0196, p=0.0101 (cis)
Height 6e-14 rs34096175 1 GCST007841 no MR -> candidate analysis
Physical function (baseline) 2e-11 rs7786022 1 GCST90565837 no MR -> candidate analysis
Body shape phenotype PC2 8e-11 rs6959005 1 GCST90832990 no MR -> candidate analysis
…and 3 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 22 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
alcohol drinking 0.361 common-variant locus no MR -> candidate analysis
insomnia 0.309 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.226 common-variant locus no MR -> candidate analysis
neoplasm 0.048 common-variant locus MR: beta=-0.0647, p=0.399 (cis)
schizophrenia 0.039 common-variant locus MR: beta=-0.113, p=0.00387 (cis)
ovarian neoplasm 0.035 common-variant locus no MR -> candidate analysis
skin aging 0.032 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 5 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=0.27, LOEUF=0.901 — LoF-tolerant
GWAS Catalog 48 unique SNPs / 96 rows
ClinVar 68 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance