ADA Gene

The ADA gene (ADA stands for "adenosine deaminase") is a protein-coding gene located on chromosome 20q13.12. The ADA gene encodes the enzyme "adenosine deaminase", which catalyzes the hydrolysis of adenosine to inosine in the purine catabolism pathway.

Several mutations have been described for this gene that are associated with human diseases related to impaired immune function, such as severe combined immunodeficiency disease (SCID), which is due to a deficiency of the ADA enzyme.

In individuals with ADA deficiency, there is a marked reduction in T, B, and NK lymphocytes. This leads to a deficiency in humoral and cellular immunity.

Adenosine deaminase (ADA) catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. It plays an important role in purine metabolism and adenosine homeostasis. The enzyme modulates signal transduction through extracellular adenosine and thus contributes indirectly to cellular signaling events.

It acts as a positive regulator of T cell coactivation by binding DPP4. Its interaction with DPP4 regulates adhesion between lymphocytes and epithelial cells.

ADA enhances the immunogenicity of dendritic cells by affecting the expression of costimulatory molecules in dendritic cells and the secretion of cytokines and chemokines. The differentiation and proliferation of CD4+ T cells is promoted. Adenosine deaminase acts as a positive modulator of the adenosine receptors ADORA1 and ADORA2A by increasing their ligand affinity through conformational change.

Diseases associated with ADA include:

Severe combined immunodeficiency (SCID), autosomal recessive, T-cell negative, B-cell negative, Nk-cell negative, due to adenosine deaminase deficiency(ADA deficiency; OMIM: 102700).

Elevated levels of adenosine deaminase are associated with congenital hemolytic anemia.

1. Arredondo-Vega FX et al (1990) Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combined immunodeficiency. J. Clin. Invest. 86: 444-452.
2. Arredondo-Vega FX et al (1994) Correct splicing despite mutation of the invariant first nucleotide of a 5-prime splice site: a possible basis for disparate clinical phenotypes in siblings with adenosine deaminase deficiency. Am J Hum Genet 54: 820-830.
3. Hershfield MS (2003) Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr Opin Immun 15: 571-577.