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Aliases for CA12 Gene

Aliases for CA12 Gene

  • Carbonic Anhydrase 12 2 3 3 5
  • Carbonic Anhydrase XII 2 3 4
  • Tumor Antigen HOM-RCC-3.1.3 3 4
  • Carbonate Dehydratase XII 3 4
  • CA-XII 3 4
  • Carbonic Dehydratase 3
  • EC 4
  • HsT18816 3
  • T18816 3
  • CAXII 3

External Ids for CA12 Gene

Previous GeneCards Identifiers for CA12 Gene

  • GC15M059403
  • GC15M056707
  • GC15M061195
  • GC15M061332
  • GC15M061402
  • GC15M063613
  • GC15M040438

Summaries for CA12 Gene

Entrez Gene Summary for CA12 Gene

  • 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]

GeneCards Summary for CA12 Gene

CA12 (Carbonic Anhydrase 12) is a Protein Coding gene. Diseases associated with CA12 include Hyperchlorhidrosis, Isolated and Degenerative Disc Disease. Among its related pathways are Translational Control and Metabolism. Gene Ontology (GO) annotations related to this gene include carbonate dehydratase activity. An important paralog of this gene is CA14.

UniProtKB/Swiss-Prot for CA12 Gene

  • Reversible hydration of carbon dioxide.

Tocris Summary for CA12 Gene

  • Carbonic anhydrases (EC are zinc-containing enzymes belonging to the lyases family, and are primarily responsible for catalyzing the reversible hydration of carbon dioxide to form bicarbonate (HCO3-) and hydrogen (H+) ions.

Gene Wiki entry for CA12 Gene

Additional gene information for CA12 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CA12 Gene

Genomics for CA12 Gene

GeneHancer (GH) Regulatory Elements for CA12 Gene

Promoters and enhancers for CA12 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15J063379 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 685.7 +1.5 1473 3.4 PKNOX1 ZSCAN4 SIN3A ZBTB7B ZBTB40 ZNF335 ZNF121 ZNF366 HSF1 RCOR1 CA12 USP3-AS1 PIR45347 GC15M064002
GH15J063370 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 33.5 +8.7 8747 4.9 PKNOX1 SREBF2 KLF17 SIN3A ZNF207 RCOR1 FOS SMARCA5 ZNF263 PHF21A CA12 LACTB RAB8B GC15M064002 PIR45347
GH15J063395 Enhancer 1.2 ENCODE dbSUPER 31.4 -14.2 -14166 1.4 ATF1 FOXA2 ARNT TCF12 ZNF766 E2F8 ZFP91 FOS ATF7 NCOA1 CA12 APH1B FBXL22 RAB8B LINC02568 ENSG00000259268
GH15J063363 Enhancer 0.9 ENCODE dbSUPER 29.9 +18.8 18774 1 TEAD4 TAL1 FOSL1 TCF12 GATA2 NCOR1 CBFA2T2 CREM MTA2 CBFA2T3 CA12 GC15M064002 PIR45347
GH15J063407 Enhancer 0.8 ENCODE 30.8 -25.7 -25676 0.2 INSM2 MZF1 FEZF1 ZNF213 ZNF366 SCRT2 RCOR1 SP3 OVOL3 TSHZ1 CA12 USP3 APH1B FBXL22 LINC02568 ENSG00000259268
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CA12 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CA12 gene promoter:
  • E47
  • Hand1
  • MyoD
  • AML1a
  • COUP
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • AREB6

Genomic Locations for CA12 Gene

Genomic Locations for CA12 Gene
60,784 bases
Minus strand
60,784 bases
Minus strand

Genomic View for CA12 Gene

Genes around CA12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CA12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CA12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CA12 Gene

Proteins for CA12 Gene

  • Protein details for CA12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Carbonic anhydrase 12
    Protein Accession:
    Secondary Accessions:
    • B2RE24
    • Q53YE5
    • Q9BWG2

    Protein attributes for CA12 Gene

    354 amino acids
    Molecular mass:
    39451 Da
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for CA12 Gene

    Alternative splice isoforms for CA12 Gene


neXtProt entry for CA12 Gene

Post-translational modifications for CA12 Gene

  • Glycosylation at posLast=162162, posLast=8080, and posLast=2828
  • Modification sites at PhosphoSitePlus

Other Protein References for CA12 Gene

No data available for DME Specific Peptides for CA12 Gene

Domains & Families for CA12 Gene

Gene Families for CA12 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted membrane proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the alpha-carbonic anhydrase family.
  • Belongs to the alpha-carbonic anhydrase family.
genes like me logo Genes that share domains with CA12: view

Function for CA12 Gene

Molecular function for CA12 Gene

UniProtKB/Swiss-Prot Function:
Reversible hydration of carbon dioxide.
UniProtKB/Swiss-Prot CatalyticActivity:
H(2)CO(3) = CO(2) + H(2)O.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA), benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide) and Foscarnet (phosphonoformate trisodium salt).
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=12.0 mM for CO(2) {ECO:0000269 PubMed:18618712};
GENATLAS Biochemistry:
carbonic anhydrase XII,39.5kDa,expressed in pancreas,kidney and salivary gland,with a truncated form (tumor associated) overexpressed in renal cell carcinomas but not mutated

Enzyme Numbers (IUBMB) for CA12 Gene

Phenotypes From GWAS Catalog for CA12 Gene

Gene Ontology (GO) - Molecular Function for CA12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004089 carbonate dehydratase activity TAS --
GO:0008270 zinc ion binding IEA --
GO:0016829 lyase activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CA12: view
genes like me logo Genes that share phenotypes with CA12: view

Human Phenotype Ontology for CA12 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CA12

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for CA12 Gene

Localization for CA12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CA12 Gene

Membrane; Single-pass type I membrane protein.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CA12 gene
Compartment Confidence
plasma membrane 5
extracellular 2
mitochondrion 2
cytosol 2
peroxisome 1
nucleus 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleus (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CA12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with CA12: view

Pathways & Interactions for CA12 Gene

genes like me logo Genes that share pathways with CA12: view

Pathways by source for CA12 Gene

2 Reactome pathways for CA12 Gene
1 PharmGKB pathway for CA12 Gene
1 KEGG pathway for CA12 Gene
2 Cell Signaling Technology pathways for CA12 Gene

Interacting Proteins for CA12 Gene

Gene Ontology (GO) - Biological Process for CA12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006730 one-carbon metabolic process IEA --
GO:0015701 bicarbonate transport TAS --
GO:0055064 chloride ion homeostasis IMP 21035102
genes like me logo Genes that share ontologies with CA12: view

No data available for SIGNOR curated interactions for CA12 Gene

Drugs & Compounds for CA12 Gene

(23) Drugs for CA12 Gene - From: DrugBank, PharmGKB, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Zonisamide Approved, Investigational Pharma blocker, Target, inhibitor Antiepileptic with anticonvulsant and mechanistic effect 69
Topiramate Approved Pharma antagonist GluR5 receptor antagonist,anticonvulsant, GluR5 antagonist; inhibits carbonic anhydrase (CA) II and IV 257
Benzthiazide Approved Pharma Target, inhibitor 0
Hydroflumethiazide Approved, Investigational Pharma Target, inhibitor 1
Brinzolamide Approved Pharma inhibitor CA II inhibitor 63

(3) Additional Compounds for CA12 Gene - From: Novoseek, Tocris, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Carbonic acid
  • [co(OH)2]
  • Dihydrogen carbonate
  • H2CO3
  • Koehlensaeure
  • Carbonate

(2) Tocris Compounds for CA12 Gene

Compound Action Cas Number
S4 High affinity and selective CA IX and CA XII inhibitor 1330061-67-0
U 104 Potent carbonic anhydrase (CA) IX and XII inhibitor 178606-66-1
genes like me logo Genes that share compounds with CA12: view

Transcripts for CA12 Gene

mRNA/cDNA for CA12 Gene

Unigene Clusters for CA12 Gene

Carbonic anhydrase XII:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CA12

Alternative Splicing Database (ASD) splice patterns (SP) for CA12 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c
SP1: - -
SP2: - - -
SP3: - -
SP5: -

Relevant External Links for CA12 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CA12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CA12 Gene

mRNA differential expression in normal tissues according to GTEx for CA12 Gene

This gene is overexpressed in Kidney - Cortex (x8.4), Skin - Not Sun Exposed (Suprapubic) (x5.1), Colon - Transverse (x4.4), and Skin - Sun Exposed (Lower leg) (x4.1).

Protein differential expression in normal tissues from HIPED for CA12 Gene

This gene is overexpressed in Nasal epithelium (45.1) and Oral epithelium (9.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CA12 Gene

NURSA nuclear receptor signaling pathways regulating expression of CA12 Gene:


SOURCE GeneReport for Unigene cluster for CA12 Gene:


mRNA Expression by UniProt/SwissProt for CA12 Gene:

Tissue specificity: Highly expressed in colon, kidney, prostate, intestine and activated lymphocytes. Expressed at much higher levels in the renal cell cancers than in surrounding normal kidney tissue. Moderately expressed in pancreas, ovary and testis.

Evidence on tissue expression from TISSUES for CA12 Gene

  • Kidney(4.9)
  • Eye(4.7)
  • Lung(4.4)
  • Nervous system(4.2)
  • Intestine(3.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CA12 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
Head and neck:
  • brain
  • ear
  • head
  • heart
  • heart valve
  • lung
genes like me logo Genes that share expression patterns with CA12: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for CA12 Gene

Orthologs for CA12 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CA12 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia CA12 34 33
  • 99.44 (n)
(Canis familiaris)
Mammalia CA12 34 33
  • 85.63 (n)
(Mus musculus)
Mammalia Car12 16 34 33
  • 83.76 (n)
(Bos Taurus)
Mammalia CA12 34 33
  • 82.58 (n)
(Rattus norvegicus)
Mammalia Car12 33
  • 82.15 (n)
(Monodelphis domestica)
Mammalia CA12 34
  • 70 (a)
(Ornithorhynchus anatinus)
Mammalia CA12 34
  • 54 (a)
(Gallus gallus)
Aves CA12 34 33
  • 66.57 (n)
(Anolis carolinensis)
Reptilia CA12 34
  • 60 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia ca12 33
  • 57.64 (n)
Str.15012 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.10362 33
(Danio rerio)
Actinopterygii LOC100537787 33
  • 56.43 (n)
CA12 34
  • 48 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8628 34
  • 17 (a)
Species where no ortholog for CA12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CA12 Gene

Gene Tree for CA12 (if available)
Gene Tree for CA12 (if available)
Evolutionary constrained regions (ECRs) for CA12: view image

Paralogs for CA12 Gene

Paralogs for CA12 Gene

(13) SIMAP similar genes for CA12 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with CA12: view

Variants for CA12 Gene

Sequence variations from dbSNP and Humsavar for CA12 Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs148438059 pathogenic, Hyperchlorhidrosis, isolated 63,327,234(-) C/T splice_acceptor_variant
rs267606694 pathogenic, Hyperchlorhidrosis, isolated, Hyperchlorhidrosis, isolated (HCHLH) [MIM:143860] 63,345,479(-) C/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs775067652 pathogenic, Hyperchlorhidrosis, isolated 63,345,543(-) G/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs879253800 pathogenic, Hyperchlorhidrosis, isolated 63,338,834(-) /AGGT coding_sequence_variant, frameshift, non_coding_transcript_variant
rs1000050632 -- 63,347,977(-) A/G/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CA12 Gene

Variant ID Type Subtype PubMed ID
nsv1035441 CNV gain 25217958
nsv1563 CNV insertion 18451855
nsv1564 CNV deletion 18451855
nsv457181 CNV loss 19166990
nsv569700 CNV loss 21841781

Variation tolerance for CA12 Gene

Residual Variation Intolerance Score: 60.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.20; 24.08% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CA12 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CA12 Gene

Disorders for CA12 Gene

MalaCards: The human disease database

(3) MalaCards diseases for CA12 Gene - From: HGMD, OMIM, ClinVar, GTR, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hyperchlorhidrosis, isolated
  • isolated hyperchlorhidrosis
degenerative disc disease
  • lumbar disc degeneration
renal cell carcinoma, nonpapillary
  • rcc
- elite association - COSMIC cancer census association via MalaCards
Search CA12 in MalaCards View complete list of genes associated with diseases


  • Hyperchlorhidrosis, isolated (HCHLH) [MIM:143860]: A disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat. {ECO:0000269 PubMed:21035102}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CA12

genes like me logo Genes that share disorders with CA12: view

No data available for Genatlas for CA12 Gene

Publications for CA12 Gene

  1. Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal localization of a carbonic anhydrase gene that is overexpressed in some renal cell cancers. (PMID: 9636197) Türeci O … Sly WS (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 22 58
  2. Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells. (PMID: 11493685) Whittington DA … Christianson DW (Proceedings of the National Academy of Sciences of the United States of America 2001) 3 4 22 58
  3. Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes. (PMID: 9770531) Ivanov SV … Lerman MI (Proceedings of the National Academy of Sciences of the United States of America 1998) 3 4 22 58
  4. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. (PMID: 21035102) Feldshtein M … Birk OS (American journal of human genetics 2010) 3 4 58
  5. Differential modulation of the active site environment of human carbonic anhydrase XII by cationic quantum dots and polylysine. (PMID: 20215053) Manokaran S … Srivastava DK (Biochimica et biophysica acta 2010) 3 22 58

Products for CA12 Gene

Sources for CA12 Gene

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