Carbonic anhydrase 9

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Carbonic anhydrase IX
Protein CA9 PDB 2HKF.png
Rendering based on PDB 2HKF.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols CA9 ; CAIX; MN
External IDs OMIM603179 MGI2447188 HomoloGene20325 ChEMBL: 3594 GeneCards: CA9 Gene
EC number
RNA expression pattern
PBB GE CA9 205199 at tn.png
More reference expression data
Species Human Mouse
Entrez 768 230099
Ensembl ENSG00000107159 ENSMUSG00000028463
UniProt Q16790 Q8VHB5
RefSeq (mRNA) NM_001216 NM_139305
RefSeq (protein) NP_001207 NP_647466
Location (UCSC) Chr 9:
35.67 – 35.68 Mb
Chr 4:
43.51 – 43.51 Mb
PubMed search [1] [2]

Carbonic anhydrase 9 (CA9/CAIX) is an enzyme that in humans is encoded by the CA9 gene.[1][2][3]

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. They show extensive diversity in tissue distribution and in their subcellular localization. CAIX is a transmembrane protein and is a tumor-associated carbonic anhydrase isoenzyme. It is over-expressed in VHL mutated clear-cell renal cell carcinoma (ccRCC) and hypoxic solid tumors, but is low-expressed in normal kidney and most other normal tissues. It may be involved in cell proliferation and transformation. This gene is mapped to 9p13-p12.[3]

CAIX has been licensed by the Dendreon Corporation. It is under development as a target for Autologous Cellular Immunotherapy. Product candidates targeted at CA9 are in preclinical development for the treatment of kidney, colon, and cervical cancer.

CAIX is considered to be one of the best cellular biomarkers of hypoxia. Furthermore, recent studies examining the association between CAIX levels and various clinicopathological outcomes suggest that CAIX expression may also be a valuable prognostic indicator for overall survival.[4] Antibodies against CAIX serve as excellent biomarkers of hypoxic regions in many solid tumors.[5]


  1. ^ Opavsky R, Pastorekova S, Zelnik V, Gibadulinova A, Stanbridge EJ, Zavada J, Kettmann R, Pastorek J (Sep 1996). "Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships". Genomics 33 (3): 480–7. doi:10.1006/geno.1996.0223. PMID 8661007. 
  2. ^ Nakagawa Y, Uemura H, Hirao Y, Yoshida K, Saga S, Yoshikawa K (Dec 1998). "Radiation hybrid mapping of the human MN/CA9 locus to chromosome band 9p12-p13". Genomics 53 (1): 118–9. doi:10.1006/geno.1998.5483. PMID 9787087. 
  3. ^ a b "Entrez Gene: CA9 carbonic anhydrase IX". 
  4. ^ Kirkpatrick JP, Rabbani, ZN, Bentley RC, Hardee ME, Karol S, Meyer J, Oosterwijk E, Havrilesky L, Secord AA, Vujaskovic Z, Dewhirst MW, Jones EL (Feb 2008). “Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer”. Biomark Insights 3:45-55.
  5. ^

Further reading[edit]

  • Nishimori I, Onishi S (2001). "Carbonic anhydrase isozymes in the human pancreas.". Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 33 (1): 68–74. doi:10.1016/s1590-8658(01)80138-9. PMID 11303978. 
  • Pastoreková S, Závadová Z, Kostál M et al. (1992). "A novel quasi-viral agent, MaTu, is a two-component system.". Virology 187 (2): 620–6. doi:10.1016/0042-6822(92)90464-Z. PMID 1312272. 
  • Pastorek J, Pastoreková S, Callebaut I et al. (1994). "Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment.". Oncogene 9 (10): 2877–88. PMID 8084592. 
  • Závada J, Závadová Z, Pastoreková S et al. (1993). "Expression of MaTu-MN protein in human tumor cultures and in clinical specimens.". Int. J. Cancer 54 (2): 268–74. doi:10.1002/ijc.2910540218. PMID 8486430. 
  • Pastoreková S, Parkkila S, Parkkila AK et al. (1997). "Carbonic anhydrase IX, MN/CA IX: analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts.". Gastroenterology 112 (2): 398–408. doi:10.1053/gast.1997.v112.pm9024293. PMID 9024293. 
  • Saarnio J, Parkkila S, Parkkila AK et al. (1998). "Immunohistochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity.". J. Histochem. Cytochem. 46 (4): 497–504. doi:10.1177/002215549804600409. PMID 9524195. 
  • Ivanov SV, Kuzmin I, Wei MH et al. (1998). "Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes.". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12596–601. doi:10.1073/pnas.95.21.12596. PMC 22876. PMID 9770531. 
  • Grabmaier K, Vissers JL, De Weijert MC et al. (2000). "Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250.". Int. J. Cancer 85 (6): 865–70. doi:10.1002/(SICI)1097-0215(20000315)85:6<865::AID-IJC21>3.0.CO;2-Q. PMID 10709109. 
  • Kivelä AJ, Parkkila S, Saarnio J et al. (2001). "Expression of transmembrane carbonic anhydrase isoenzymes IX and XII in normal human pancreas and pancreatic tumours.". Histochem. Cell Biol. 114 (3): 197–204. PMID 11083462. 
  • Wingo T, Tu C, Laipis PJ, Silverman DN (2001). "The catalytic properties of human carbonic anhydrase IX.". Biochem. Biophys. Res. Commun. 288 (3): 666–9. doi:10.1006/bbrc.2001.5824. PMID 11676494. 
  • Kivela AJ, Saarnio J, Karttunen TJ et al. (2001). "Differential expression of cytoplasmic carbonic anhydrases, CA I and II, and membrane-associated isozymes, CA IX and XII, in normal mucosa of large intestine and in colorectal tumors.". Dig. Dis. Sci. 46 (10): 2179–86. doi:10.1023/A:1011910931210. PMID 11680594. 
  • Koukourakis MI, Giatromanolaki A, Sivridis E et al. (2002). "Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy.". Clin. Cancer Res. 7 (11): 3399–403. PMID 11705854. 
  • Grabmaier K, de Weijert M, Uemura H et al. (2002). "Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies.". Urology 60 (2): 357–62. doi:10.1016/S0090-4295(02)01711-9. PMID 12137853. 
  • Kaluz S, Kaluzová M, Chrastina A et al. (2002). "Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3'-kinase.". Cancer Res. 62 (15): 4469–77. PMID 12154057. 
  • Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Swinson DE, Jones JL, Richardson D et al. (2003). "Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer.". J. Clin. Oncol. 21 (3): 473–82. doi:10.1200/JCO.2003.11.132. PMID 12560438. 
  • Bui MH, Seligson D, Han KR et al. (2003). "Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy.". Clin. Cancer Res. 9 (2): 802–11. PMID 12576453.