CausalSentinel

Protein Dossier — CA5A (Carbonic anhydrase 5A, mitochondrial)

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
Body mass index (BMI) 0.0318 0.0122 0.00907 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.323 0.125 0.00965 Wald ratio 1 trans NA
Lung cancer -0.206 0.0869 0.0177 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.299 0.134 0.0258 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bone disorder 0.403 0.181 0.0258 Wald ratio 1 trans NA
Diagnoses - main ICD10: K20 Oesophagitis 0.219 0.1 0.0283 Wald ratio 1 trans NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.75 0.82 0.0327 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.235 0.11 0.0335 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.155 0.0756 0.0402 Wald ratio 1 trans NA
Weight 0.0213 0.0108 0.0478 Wald ratio 1 trans NA
Lung adenocarcinoma -0.247 0.132 0.0614 Wald ratio 1 trans NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.192 0.106 0.0697 Wald ratio 1 trans NA
…and 70 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

40 association rows across 25 traits (34 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 CA5A levels 3e-3386 rs55870502 4 GCST90859825 no MR -> candidate analysis
AGXT/CA5A protein level ratio 6e-3164 rs7186698 1 GCST90313204 no MR -> candidate analysis
ADH4/CA5A protein level ratio 4e-3116 rs7186698 1 GCST90313189 no MR -> candidate analysis
CA5A/GSTA1 protein level ratio 8e-3008 rs7186698 1 GCST90313591 no MR -> candidate analysis
CA5A/KRT18 protein level ratio 1e-2981 rs7186698 1 GCST90313592 no MR -> candidate analysis
CA5A/SULT2A1 protein level ratio 2e-2715 rs7186698 1 GCST90313593 no MR -> candidate analysis
CA5A/GRPEL1 protein level ratio 7e-2565 rs7186698 1 GCST90313590 no MR -> candidate analysis
CA5A protein levels 9e-171 rs8053752 10 GCST90468514 no MR -> candidate analysis
Carbonic anhydrase 5A,mitochondrial levels 3e-155 rs55870502 1 GCST90179238 no MR -> candidate analysis
Basophil percentage of granulocytes 9e-13 rs8056952 1 GCST004634 no MR -> candidate analysis
Basophil percentage of white cells 1e-12 rs8056952 1 GCST004631 no MR -> candidate analysis
Hair colour (natural, before greying): Red (UKB data field 1 3e-12 rs182303497 1 GCST90041837 no MR -> candidate analysis
…and 13 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 106 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
hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency 0.82 established (curated) no MR -> candidate analysis
urolithiasis 0.401 common-variant locus no MR -> candidate analysis
hereditary disease 0.317 established (curated) no MR -> candidate analysis
placenta praevia 0.308 common-variant locus no MR -> candidate analysis
osteoarthritis 0.208 common-variant locus no MR -> candidate analysis
multinodular goiter 0.093 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.091 common-variant locus no MR -> candidate analysis
pulmonary embolism 0.09 common-variant locus no MR -> candidate analysis
obesity disorder 0.057 common-variant locus no MR -> candidate analysis
breast carcinoma 0.037 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.06 common-variant locus no MR -> candidate analysis
Jaundice 0.058 common-variant locus no MR -> candidate analysis
hidradenitis 0.052 common-variant locus no MR -> candidate analysis
alcohol drinking 0.048 common-variant locus no MR -> candidate analysis
stroke disorder 0.048 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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 (Carbonic anhydrase 5A, mitochondrial)
gnomAD constraint pLI=6.5e-08, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 125 unique SNPs / 277 rows
ClinVar 315 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance