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ADA2

adenosine deaminase 2

The ADA2 gene provides instructions for making adenosine deaminase 2, an enzyme involved in immune system function, particularly in regulating inflammation and immune cell development. ADA2 encodes adenosine deaminase 2, an extracellular enzyme that breaks down adenosine and 2'-deoxyadenosine.

Chromosome 22q11.1 Autosomal recessive HGNC:1839 Tier C
ADA2 22q11.1 p arm q arm 22

ADA2 is located on the long (q) arm of chromosome 22, at band 22q11.1. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
ADA2 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ADA2 gene produces the enzyme adenosine deaminase 2, which acts outside of cells. This enzyme metabolises adenosine and 2'-deoxyadenosine. Research indicates that ADA2 is crucial for immune system function, acting as a growth factor that supports the development of immune cells such as macrophages, which are important in inflammatory processes.

What the gene does

The ADA2 gene encodes adenosine deaminase 2, an enzyme that facilitates the deamination of adenosine and 2'-deoxyadenosine in the extracellular environment. This enzymatic activity is distinct from adenosine deaminase 1 (ADA1), which is produced by the ADA gene and performs a similar metabolic role inside cells. Beyond its role in nucleoside metabolism, ADA2 is believed to function as a growth factor, supporting the proliferation and differentiation of specific cell types, particularly within the immune system. It influences the development of macrophages, which are white blood cells central to the body's inflammatory response. Macrophages can either promote or reduce inflammation, suggesting ADA2 contributes to modulating these immune responses.

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Chromosome location

The ADA2 gene is located on chromosome 22, specifically at position 22q11.1. This means it is found on the long (q) arm of chromosome 22, within band 1 of region 1.

Protein structure

The adenosine deaminase 2 protein consists of 511 amino acids. It has specific functional regions, including a Dimerisation region, located between amino acids 30 and 100, which likely enables the protein to form a dimer. Additionally, it contains a PRB domain, found between amino acids 127 and 185; the precise function of this domain in ADA2 is still under investigation.

Domain map · 511 amino acids
Dimerization (30–100)PRB domain (127–185)Dimerization30–100PRB domain127–1851~256511
Region - functional region
🧬 Explore 3D structure on AlphaFold
UniProt:Q9NZK5Length:511 aaStructure:AlphaFold

Key variants

Variants within the ADA2 gene can alter how the adenosine deaminase 2 enzyme functions or is produced. These genetic changes may lead to reduced or absent enzyme activity, which is associated with specific health conditions. The impact of a particular variant depends on its nature and its location within the gene. More than 60 pathogenic variants have been identified in the ADA2 gene.

599
Total variants catalogued in ClinVar
View all on ClinVar →
90 Pathogenic / Likely pathogenic 249 Uncertain significance 234 Benign / Likely benign 26 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1058_1061del
Deletion
 p.Tyr353fs Pathogenic ★★☆☆ Deficiency of adenosine deaminase 2
c.1072G>A
single nucleotide variant
 p.Gly358Arg Pathogenic ★★☆☆ not provided
c.1078A>G
single nucleotide variant
 p.Thr360Ala Pathogenic ★★☆☆ Sneddon syndrome
c.1110C>A
single nucleotide variant
 p.Asn370Lys Pathogenic/Likely pathogenic ★★☆☆ Inherited Immunodeficiency Diseases
c.1147G>A
single nucleotide variant
 p.Gly383Ser Pathogenic/Likely pathogenic ★★☆☆ Sneddon syndrome
c.1303_1319del
Deletion
 p.His434_Pro435insTer Pathogenic ★★☆☆ Deficiency of adenosine deaminase 2
c.1358A>G
single nucleotide variant
 p.Tyr453Cys Pathogenic/Likely pathogenic ★★☆☆ Deficiency of adenosine deaminase 2
c.1373T>A
single nucleotide variant
 p.Val458Asp Pathogenic/Likely pathogenic ★★☆☆ Sneddon syndrome
c.1397_1403del
Deletion
 p.Lys466fs Pathogenic/Likely pathogenic ★★☆☆ Deficiency of adenosine deaminase 2
c.139G>A
single nucleotide variant
 p.Gly47Arg Pathogenic/Likely pathogenic ★★☆☆ Deficiency of adenosine deaminase 2

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ADA2 gene result in deficiency of ADA2 (DADA2). This is an autosomal recessive disorder characterised by dysregulated inflammation affecting various organs and tissues, frequently presenting as vasculitis.

Inheritance pattern

Conditions caused by pathogenic ADA2 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous ADA2 carrier status across ancestry groups?

UK clinical status

The ADA2 gene is included in several expert-curated panels within the UK's NHS Genomic Medicine Service via PanelApp. It is featured in panels for Autoinflammatory disorders (R413), Cytopenia - NOT Fanconi anaemia (R91), Cytopenias and congenital anaemias, Hereditary neuropathy or pain disorder (R78), Primary immunodeficiency or monogenic inflammatory bowel disease (R15), Rare anaemia (R92), and Rare genetic inflammatory skin disorders (R332), indicating its relevance in diagnosing a range of conditions.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Autoinflammatory disorders · R413 NHS GMS → Cytopenia - NOT Fanconi anaemia · R91 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Primary immunodeficiency or monogenic inflammatory bowel disease · R15 NHS GMS → Rare anaemia · R92 NHS GMS → Rare genetic inflammatory skin disorders · R332 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary role of the ADA2 gene?

The ADA2 gene provides instructions for making adenosine deaminase 2, an extracellular enzyme. This enzyme breaks down adenosine and 2'-deoxyadenosine and acts as a growth factor, influencing the development of immune cells like macrophages and regulating inflammation.

What condition is associated with variants in the ADA2 gene?

Variants in the ADA2 gene are associated with deficiency of ADA2 (DADA2). This is an inherited condition characterised by chronic inflammation that can affect various body systems, particularly blood vessels.

How is DADA2 inherited?

DADA2 is inherited in an autosomal recessive pattern. This means an individual must inherit two pathogenic variants, one from each parent, to develop the condition. Individuals with only one pathogenic variant are typically carriers and do not show symptoms.

References

  1. Meyts I, Aksentijevich I. Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment. Journal of clinical immunology. 2018. PMID: 29951947
  2. Van Montfrans JM, Hartman EA, Braun KP. Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations. Rheumatology (Oxford, England). 2016. PMID: 26867732
  3. Nanthapisal S, Murphy C, Omoyinmi E. Deficiency of Adenosine Deaminase Type 2: A Description of Phenotype and Genotype in Fifteen Cases. Arthritis & rheumatology (Hoboken, N.J.). 2016. PMID: 27059682
  4. Zhou Q, Yang D, Ombrello AK. Early-onset stroke and vasculopathy associated with mutations in ADA2. The New England journal of medicine. 2014. PMID: 24552284
  5. Navon Elkan P, Pierce SB, Segel R. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. The New England journal of medicine. 2014. PMID: 24552285
  6. Zavialov AV, Yu X, Spillmann D. Structural basis for the growth factor activity of human adenosine deaminase ADA2. The Journal of biological chemistry. 2010. PMID: 20147294
  7. Zavialov AV, Engström A. Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. The Biochemical journal. 2005. PMID: 15926889
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 6 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .