Carbonic anhydrase 12

CA12
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JCZ, 1JD0, 4HT2, 4KP5, 4KP8, 4Q0L, 4QJ0, 4QJO, 4QJW, 4WW8
Identifiers
Aliases	CA12, CAXII, HsT18816, CA-XII, T18816, carbonic anhydrase 12
External IDs	OMIM: 603263; MGI: 1923709; HomoloGene: 20327; GeneCards: CA12; OMA:CA12 - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q22.2 Start 63,321,378 bp[1] End 63,381,846 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 C Start 66,620,968 bp[2] End 66,674,127 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla kidney tubule skin of thigh Epithelium of choroid plexus mucosa of colon mucosa of sigmoid colon vulva skin of hip glomerulus mucosa of pharynx Top expressed in choroid plexus of fourth ventricle retinal pigment epithelium Epithelium of choroid plexus stria vascularis right kidney lip parotid gland human kidney vestibular membrane of cochlear duct submandibular gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function carbonate dehydratase activity zinc ion binding lyase activity metal ion binding carbonic anhydrase Cellular component integral component of membrane plasma membrane membrane Biological process bicarbonate transport chloride ion homeostasis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 771 76459 Ensembl ENSG00000074410 ENSMUSG00000032373 UniProt O43570 Q8CI85 RefSeq (mRNA) NM_206925 NM_001218 NM_001293642 NM_178396 NM_001306148 RefSeq (protein) NP_001209 NP_001280571 NP_996808 NP_001293077 NP_848483 Location (UCSC) Chr 15: 63.32 – 63.38 Mb Chr 9: 66.62 – 66.67 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Carbonic anhydrase 12 is an enzyme that in humans is encoded by the CA12 gene.^[5][6]

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in various 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 highly expressed in normal tissues, such as kidney, colon and pancreas, and has been overexpressed in 10% of clear cell renal carcinomas. Two transcript variants encoding different isoforms have been identified for this gene.^[6]

Loss of function mutations in the CAXII gene result in defects in fluids and carbonate secretions in the following diseases:

1) Cystic fibrosis-like syndrome with normal cystic fibrosis transmembrane conductance regulator (CFTR) protein levels ^{[7][8][9][10][11][12]}

2) Pancreatitis^[13][14]

3) Sjögren's syndrome^[14][15]

4) Xerostomia or dry mouth syndrome^[9][10][11]

CAXII, with either the His121Gln or Glu143Lys mutation, localizes to basolateral membranes of polarized MDCK cells similar to the wild type enzyme, indicating no deleterious effect on subcellular location.^[14]

The Glu143Lys (E143K) loss-of-function variant of the CAXII gene is associated with a rare autosomal recessive condition named isolated hyperchlorhidrosis (carbonic anhydrase XII deficiency). Typically, this variant results in excessive sodium chloride loss, usually through sweating, and presents pathologically as episodic hyponatremic dehydration with bouts of vomiting and/or diarrhoea.

Generally, CAXII mutant enzymes show reduced activity. These observations make it difficult to explain the mechanism for the autosomal recessive disorder of hyponatremia, causing salt wasting in sweat due to mutant CAXII.^[7][8]

In a separate study, researchers observed that mutant enzyme activity is completely reduced at physiological concentrations of sodium chloride.^[14] Thus, loss of the function of CAXII in sweat glands and lungs is the molecular basis for cystic fibrosis patients with normal CFTR levels.^[14]

Differential modulation of the active site environment of CAXII by cationic quantum dots and polylysine helps design CAXII specific activators and inhibitors of the enzyme.^[16] CAXII specific inhibition provides a tool to interfere with cell proliferation, resulting in cell apoptosis in T-cell lymphomas.^[17]

Serum CAXII levels should be applicable as a sero-diagnostic marker for lung cancer.^[18]

The 2017 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as: Abdul Waheed; William S Sly (19 April 2017). "Carbonic anhydrase XII functions in health and disease". Gene. Gene Wiki Review Series. 623: 33–40. doi:10.1016/J.GENE.2017.04.027. ISSN 0378-1119. PMC 5851007. PMID 28433659. Wikidata Q39256524.

• Human CA12 genome location and CA12 gene details page in the UCSC Genome Browser.