CA12

Chr 15AR

carbonic anhydrase 12

Also known as: CA-XII, CAXII, HsT18816, T18816

NCBI Gene: 771ENSG00000074410UniProt: O43570

Carbonic anhydrase XII is a membrane-bound zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide, participating in acid-base balance and fluid formation processes. Mutations cause isolated hyperchlorhidrosis, characterized by excessive sweating with high chloride content, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variation (pLI near zero, LOEUF 1.33), suggesting tolerance to protein-truncating variants.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Hyperchlorhidrosis, isolatedMIM #143860
AR
1
Active trials
29
Pubs (1 yr)
17
P/LP submissions
13%
P/LP missense
1.33
LOEUF
DN
Mechanism· predicted
Clinical Summary— CA12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 64 VUS of 142 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — CA12
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.000
Z-score 0.44
OE 0.89 (0.62–1.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.18Z-score
OE missense 1.04 (0.92–1.17)
203 obs / 195.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.89 (0.62–1.33)
0≤0.351.4
Missense OE1.04 (0.92–1.17)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 18 / 20.1Missense obs/exp: 203 / 195.8Syn Z: -0.92
DN
0.7130th %ile
GOF
0.6052th %ile
LOF
0.2874th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic4
VUS64
Likely Benign13
Benign30
Conflicting1
11
Pathogenic
4
Likely Pathogenic
64
VUS
13
Likely Benign
30
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
8
0
11
Likely Pathogenic
2
0
2
0
4
VUS
1
59
4
0
64
Likely Benign
0
5
1
7
13
Benign
0
2
24
4
30
Conflicting
—1
Total4683911123

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CA12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A dual-quenched photoelectrochemical immunosensor based on a CdS/SrTiO3 heterojunction for CA12-5 sensitive detection.
Zhang N et al.·Anal Methods
2026
A case report on pseudohypoaldosteronism with a pathogenic mutation of CA12 causes autosomal recessive isolated hyperchlorhidrosis disorder.
Alanazi YA.·J Family Med Prim Care
2025Open AccessCase report
WTAP mediates IL-1β-induced chondrocyte injury by enhancing CA12 mRNA stability depending on m6A modification.
Deng G et al.·J Orthop Surg Res
2024Open Access
Malignant transformation of ovarian mature cystic teratoma with rupture, elevated serum CA199, CA12, CEA: A case report.
Chen L et al.·Medicine (Baltimore)
2024Open AccessCase report
Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition.
Deben C et al.·J Exp Clin Cancer Res
2024Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients