ADA2 gene
adenosine deaminase 2
The ADA2 gene provides instructions for making an enzyme called adenosine deaminase 2. This enzyme breaks down molecules called adenosine and 2'-deoxyadenosine. Because this enzyme functions in the spaces between cells, it is described as extracellular. Another form of the enzyme, adenosine deaminase 1, breaks down the same molecules inside cells. This other version of the enzyme is produced from the ADA gene.
Researchers are still working to determine the functions of adenosine deaminase 2. Studies suggest that it acts as a growth factor, which means that it stimulates cell growth and division. In particular, the enzyme appears to be involved in the growth and development of certain immune system cells, including macrophages, which are a type of white blood cell that plays a critical role in inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). Some macrophages are pro-inflammatory, meaning they promote inflammation, while others are anti-inflammatory, meaning they reduce inflammation.
Related Information
More than 60 mutations in the ADA2 gene have been found to cause adenosine deaminase 2 deficiency, a disorder characterized by abnormal inflammation of various organs and tissues, particularly the blood vessels (vasculitis). These mutations severely reduce or eliminate the function of adenosine deaminase 2. Researchers do not fully understand how a shortage (deficiency) of this enzyme's activity leads to vasculitis and immune system abnormalities. They speculate that the enzyme deficiency may disrupt the balance between pro-inflammatory and anti-inflammatory macrophages in various tissues, leading to a buildup of pro-inflammatory macrophages and abnormal inflammation.
Related Information
Cytogenetic Location: 22q11.1, which is the long (q) arm of chromosome 22 at position 11.1
Molecular Location: base pairs 17,178,790 to 17,221,854 on chromosome 22 (Homo sapiens Annotation Release 109, GRCh38.p12) (NCBI)
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Related Information
- OMIM: CAT EYE SYNDROME CHROMOSOME REGION, CANDIDATE 1
- Meyts I, Aksentijevich I. Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment. J Clin Immunol. 2018 Jun 27. doi: 10.1007/s10875-018-0525-8. [Epub ahead of print] Review.
- Nanthapisal S, Murphy C, Omoyinmi E, Hong Y, Standing A, Berg S, Ekelund M, Jolles S, Harper L, Youngstein T, Gilmour K, Klein NJ, Eleftheriou D, Brogan PA. Deficiency of Adenosine Deaminase Type 2: A Description of Phenotype and Genotype in Fifteen Cases. Arthritis Rheumatol. 2016 Sep;68(9):2314-22. doi: 10.1002/art.39699.
- Navon Elkan P, Pierce SB, Segel R, Walsh T, Barash J, Padeh S, Zlotogorski A, Berkun Y, Press JJ, Mukamel M, Voth I, Hashkes PJ, Harel L, Hoffer V, Ling E, Yalcinkaya F, Kasapcopur O, Lee MK, Klevit RE, Renbaum P, Weinberg-Shukron A, Sener EF, Schormair B, Zeligson S, Marek-Yagel D, Strom TM, Shohat M, Singer A, Rubinow A, Pras E, Winkelmann J, Tekin M, Anikster Y, King MC, Levy-Lahad E. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014 Mar 6;370(10):921-31. doi: 10.1056/NEJMoa1307362. Epub 2014 Feb 19.
- Van Montfrans JM, Hartman EA, Braun KP, Hennekam EA, Hak EA, Nederkoorn PJ, Westendorp WF, Bredius RG, Kollen WJ, Schölvinck EH, Legger GE, Meyts I, Liston A, Lichtenbelt KD, Giltay JC, Van Haaften G, De Vries Simons GM, Leavis H, Sanders CJ, Bierings MB, Nierkens S, Van Gijn ME. Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations. Rheumatology (Oxford). 2016 May;55(5):902-10. doi: 10.1093/rheumatology/kev439. Epub 2016 Feb 10.
- Zavialov AV, Engström A. Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. Biochem J. 2005 Oct 1;391(Pt 1):51-7.
- Zavialov AV, Yu X, Spillmann D, Lauvau G, Zavialov AV. Structural basis for the growth factor activity of human adenosine deaminase ADA2. J Biol Chem. 2010 Apr 16;285(16):12367-77. doi: 10.1074/jbc.M109.083527. Epub 2010 Feb 9.
- Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffmann P, Negro A, Tsai WL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CC, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinun M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014 Mar 6;370(10):911-20. doi: 10.1056/NEJMoa1307361. Epub 2014 Feb 19.