CA12

Chr 15

carbonic anhydrase 12

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

NCBI Gene: 771 ENSG00000074410 UniProt: 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.

ResearchSummary from RefSeq, OMIM, UniProt

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2014]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHyperchlorhidrosis, isolated

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in CA12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

467 rare PASS variants

Rare truncating (LoF)

1 in 330

78 rare PASS variants

Rare synonymous (reference)

1 in 180

214 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CA12; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 700
South Asian	~43k	1 in 73	1 in 880
Remaining (unassigned)	~30k	1 in 100	1 in 490
European (Finnish)	~27k	1 in 410	1 in 890
Admixed American	~22k	1 in 150	1 in 3,700
African / African American	~21k	1 in 96	1 in 1,100
East Asian	~20k	1 in 260	1 in 500
Ashkenazi Jewish	~13k	1 in 900	1 in 1,400
Middle Eastern	~2,884	1 in 76	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 11 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 11.? see exons ↓