CausalSentinel

Protein Dossier — CA8 (Carbonic anhydrase-related protein)

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: I83 Varicose veins of lower extremities 0.27 0.0698 1.10e-04 Wald ratio 1 cis NA
Endometrioid ovarian cancer -0.447 0.155 0.004 Wald ratio 1 cis NA
Thalamus volume -93 33.2 0.00507 Wald ratio 1 cis NA
High grade serous ovarian cancer -0.236 0.085 0.00549 Wald ratio 1 cis NA
Schizophrenia -0.154 0.0574 0.00744 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.169 0.0638 0.00803 Wald ratio 1 cis NA
Ovarian cancer -0.185 0.0715 0.00984 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.224 0.0877 0.0108 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0314 0.0133 0.0185 Wald ratio 1 cis NA
Neo-conscientiousness -0.881 0.401 0.0278 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.459 0.218 0.0352 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.151 0.0739 0.0417 Wald ratio 1 cis NA
…and 79 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

18 association rows across 14 traits (13 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
Carbonic anhydrase-related protein levels 7e-105 rs140904427 1 GCST90246810 no MR -> candidate analysis
Serum levels of protein CA8 2e-25 rs7009482 1 GCST90086724 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Large HDL ratio 2e-21 rs117065418 1 GCST90827800 no MR -> candidate analysis
Red blood cell erythrocyte count (UKB data field 30010) 3e-14 rs7813325 1 GCST90468098 no MR -> candidate analysis
Blood protein levels 6e-14 rs7009482 1 GCST006585 no MR -> candidate analysis
Red blood cell count 8e-13 rs34254518 4 GCST90002363 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 4e-12 rs59743106 1 GCST90838669 no MR -> candidate analysis
Hemoglobin 1e-10 rs11345369 2 GCST90002384 no MR -> candidate analysis
Refractive error 3e-10 rs2681536 1 GCST90841196 no MR -> candidate analysis
Parkinson’s disease 6e-8 rs144074972 1 GCST003984 no MR -> candidate analysis
Total amyloid (SNP x SNP interaction) 2e-7 rs4894942 x rs2242154 1 GCST010339 no MR -> candidate analysis
Resistance to COVID-19 infection (Exposed negative vs positi 2e-6 rs9643367 1 GCST90255358 no MR -> candidate analysis
…and 2 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 1689 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
Dysequilibrium syndrome 0.779 established (curated) no MR -> candidate analysis
Rare hereditary ataxia 0.608 established (curated) no MR -> candidate analysis
cerebellar ataxia, intellectual disability, and dysequilibrium 0.608 established (curated) no MR -> candidate analysis
schizophrenia 0.51 common-variant locus MR: beta=-0.154, p=0.00744 (cis)
bilirubin metabolism disease 0.44 common-variant locus no MR -> candidate analysis
skin disorder 0.408 common-variant locus no MR -> candidate analysis
psoriasis 0.397 common-variant locus MR: beta=0.0996, p=0.376 (cis)
alcohol drinking 0.392 common-variant locus no MR -> candidate analysis
stroke disorder 0.363 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.362 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.355 common-variant locus no MR -> candidate analysis
Increased total eosinophil count 0.355 common-variant locus no MR -> candidate analysis
muscular disease 0.353 common-variant locus no MR -> candidate analysis
facial morphology 0.316 common-variant locus no MR -> candidate analysis
hereditary disease 0.312 established (curated) no MR -> candidate analysis

Of the 15 rows above, 13 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=0.00093, LOEUF=0.758 — LoF-tolerant
GWAS Catalog 31 unique SNPs / 61 rows
ClinVar 130 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance