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ADA2

adenosine deaminase 2

The ADA2 gene provides instructions for producing the adenosine deaminase 2 enzyme, which is involved in immune system regulation and inflammation processes. The ADA2 gene is critical for the production of adenosine deaminase 2, an enzyme found outside cells that helps break down adenosine.

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.

Explore chromosome 22 in the library →

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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 encodes for adenosine deaminase 2, an extracellular enzyme that breaks down adenosine and 2'-deoxyadenosine. Unlike adenosine deaminase 1, which acts inside cells, ADA2 functions in the spaces between cells. Research suggests ADA2 is a growth factor, stimulating cell growth and division, particularly within immune system cells like macrophages.

What the gene does

The adenosine deaminase 2 enzyme, encoded by the ADA2 gene, is primarily involved in breaking down molecules such as adenosine and 2'-deoxyadenosine in the extracellular space. This enzyme is crucial for the proper development and function of immune system cells, including macrophages. Macrophages are a type of white blood cell that are central to the body's inflammatory responses, with some promoting inflammation and others helping to reduce it. The precise mechanisms by which ADA2 influences these processes are still being investigated, but it is understood to be a growth factor that encourages cellular proliferation.

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Chromosome location

The ADA2 gene is located on chromosome 22 at position q11.1. This genomic location specifies its position on the long (q) arm of chromosome 22, within region 1, band 1, sub-band 1.

Protein structure

The adenosine deaminase 2 protein consists of 511 amino acids. It features a Dimerization region spanning amino acids 30-100, which is important for the protein to form its functional dimeric structure. Additionally, a PRB domain is present between amino acids 127-185, though its specific function within the enzyme 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

Genetic variations within the ADA2 gene can alter the function or production of the adenosine deaminase 2 enzyme. Over 60 different genetic changes, often referred to as mutations, have been identified. These variations can range from single base pair changes to larger deletions or insertions, and they can significantly reduce or eliminate the enzyme's activity.

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/Likely 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 are associated with deficiency of ADA2 (DADA2). This is an autosomal recessive condition characterised by systemic inflammation affecting various organs and tissues, particularly the blood vessels, leading to vasculitis. The severity of the condition can vary widely among affected individuals.

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 NHS Genomic Medicine Service national testing panels in the UK. It is assessed for a range of conditions including autoinflammatory disorders, cytopenias, rare anaemia, and primary immunodeficiency. It is also part of research efforts related to COVID-19 and hereditary neuropathy or pain disorders.

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 function of the ADA2 gene?

The ADA2 gene provides instructions for the adenosine deaminase 2 enzyme, which breaks down adenosine outside cells. This enzyme is important for the growth and development of immune cells, particularly macrophages, and plays a role in the body's inflammatory responses.

What is deficiency of ADA2 (DADA2)?

DADA2 is an autosomal recessive condition caused by mutations in the ADA2 gene. It leads to a lack of functional adenosine deaminase 2 enzyme, resulting in abnormal inflammation that can affect various parts of the body, including blood vessels.

How is the ADA2 gene inherited?

The ADA2 gene is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic variant, one from each parent, to develop a condition like DADA2. Carriers, with one copy, typically 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 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .