ADA — adenosine deaminase

30 sources retrieved · Most recent: April 2026 · Index updated 3 months ago

269PubMed Papers

#1,369 · top 7% of 19K genes

21Diseases

top 9%

3Drugs

top 52%

165Pathogenic Variants

top 8%

FDA Approved TargetOMIM Disease GeneVariant-RichExperimental GO EvidenceSwiss-Prot Reviewed

adenosine metabolic processlysosomeexternal side of plasma membranenegative regulation of adenosine receptor signaling pathwaySevere combined immunodeficiency due to adenosine deaminase deficiencysevere combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiencypartial adenosine deaminase deficiencysevere combined immunodeficiency

AI Summary

ADA encodes adenosine deaminase, a crucial enzyme in purine metabolism that catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine to maintain adenosine homeostasis. The enzyme plays a vital role in immune system function, as ADA deficiency causes severe combined immunodeficiency (SCID), a fatal childhood disorder characterized by profound T-cell dysfunction and susceptibility to infections 1. Gene therapy approaches using retroviral vectors to transfer the ADA gene into patient lymphocytes have successfully restored enzyme activity and immune function, demonstrating that genetically corrected T cells can survive in vivo and reconstitute specific immune responses 2. Clinical treatment with PEGylated ADA enzyme replacement therapy (both ADAGEN and the newer elapegademase) effectively increases plasma ADA activity and promotes immune reconstitution, including T cell recovery and thymus development 3. Beyond its metabolic role, ADA contributes to cellular signaling by modulating extracellular adenosine levels and enhancing T-cell activation. Genetic polymorphisms in ADA have been associated with increased susceptibility to certain infections, including tuberculous pericarditis 4. The enzyme's critical role in immune function makes it an important target for therapeutic intervention in immunodeficiency disorders.

Sources cited

ADA deficiency causes severe combined immunodeficiency (SCID), a fatal childhood immunodeficiency disease

PMID: 2081198

Retroviral-mediated ADA gene transfer into human ADA-deficient T lymphocytes restores enzyme activity, proliferative potential, and specific immune functions

PMID: 1325209

PEGylated ADA enzyme replacement therapy (elapegademase and ADAGEN) increases plasma ADA activity and promotes immune reconstitution including T cell recovery

PMID: 31989577

ADA gene polymorphisms are associated with increased risk of tuberculous pericarditis

PMID: 30017738

⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.

Disease Associations21

Severe combined immunodeficiency due to adenosine deaminase deficiencyOpen Targets

0.86Strong

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiencyOpen Targets

0.86Strong

partial adenosine deaminase deficiencyOpen Targets

0.66Moderate

severe combined immunodeficiencyOpen Targets

0.65Moderate

Omenn syndromeOpen Targets

0.46Moderate

T-B- severe combined immunodeficiencyOpen Targets

0.46Moderate

T-B+ severe combined immunodeficiencyOpen Targets

0.46Moderate

T+ B+ severe combined immunodeficiencyOpen Targets

0.46Moderate

neoplasmOpen Targets

0.40Weak

anemiaOpen Targets

0.37Weak

hairy cell leukemiaOpen Targets

0.37Weak

type 2 diabetes mellitusOpen Targets

0.37Weak

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets

0.34Weak

chronic lymphocytic leukemiaOpen Targets

0.30Weak

graft versus host diseaseOpen Targets

0.29Weak

diabetes mellitusOpen Targets

0.27Weak

abscessOpen Targets

0.24Weak

cellulitisOpen Targets

0.24Weak

gastrointestinal defects and immunodeficiency syndrome 1Open Targets

0.19Weak

gastrointestinal defect and immunodeficiency syndromeOpen Targets

0.18Weak

Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiencyUniProt

Pathogenic Variants165

NM_000022.4(ADA):c.606+1G>TLikely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024

NM_000022.4(ADA):c.516C>A (p.Tyr172Ter)Likely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 172

NM_000022.4(ADA):c.511A>T (p.Lys171Ter)Likely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 171

NM_000022.4(ADA):c.603C>A (p.Tyr201Ter)Likely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 201

NM_000022.4(ADA):c.976-1G>CPathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024

NM_000022.4(ADA):c.986C>T (p.Ala329Val)Pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency|not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|ADA-related disorder

★★★☆2024→ Residue 329

NM_000022.4(ADA):c.975+1G>APathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency|Severe combined immunodeficiency disease

★★★☆2024

NM_000022.4(ADA):c.763G>T (p.Glu255Ter)Likely pathogenic

not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 255

NM_000022.4(ADA):c.736C>T (p.Gln246Ter)Pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 246

NM_000022.4(ADA):c.603C>G (p.Tyr201Ter)Pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 201

NM_000022.4(ADA):c.646G>A (p.Gly216Arg)Pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency|not provided|ADA-related disorder

★★★☆2024→ Residue 216

NM_000022.4(ADA):c.845G>A (p.Arg282Gln)Pathogenic

not specified|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency|Severe combined immunodeficiency disease

★★★☆2024→ Residue 282

NM_000022.4(ADA):c.1078+2T>ALikely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024

NM_000022.4(ADA):c.890C>T (p.Pro297Leu)Likely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2024→ Residue 297

NM_000022.4(ADA):c.363-2A>GLikely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2023

NM_000022.4(ADA):c.396dup (p.Val133fs)Pathogenic

Severe combined immunodeficiency disease|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2023→ Residue 133

NM_000022.4(ADA):c.632G>A (p.Arg211His)Pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency|not provided

★★★☆2023→ Residue 211

NM_000022.4(ADA):c.201C>G (p.Tyr67Ter)Likely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2023→ Residue 67

NM_000022.4(ADA):c.219-2A>GLikely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

★★★☆2023

NM_000022.4(ADA):c.703C>T (p.Arg235Trp)Likely pathogenic

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency|ADA-related disorder

★★★☆2023→ Residue 235

Drug Targets03

AUTOLOGOUS CD34+ ENRICHED CELL FRACTION THAT CONTAINS CD34+ CELLS TRANSDUCED WITH RETROVIRAL VECTOR THAT ENCODES FOR THE HUMAN ADA CDNA SEQUENCEApproved

ADA exogenous gene

severe combined immunodeficiency

COFORMYCINPhase I

Adenosine deaminase inhibitor

leukemia

PENTOSTATINApproved

Adenosine deaminase inhibitor

anemia

Tissue Expression6 tissues

Bone Marrow

100%

Lung

57%

Heart

42%

Liver

23%

Ovary

16%

Brain

11%

Gene Interaction Network6 neighbors

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Structure2 PDB hits

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PDB3IAR · 1.52 Å · X-ray

View on RCSB

ConstraintgnomAD v4.1

LOEUFⓘ

1.18LoF Tolerant

pLIⓘ

0.00Tolerant

Observed/Expected LoF0.92 [0.73–1.18]

Rankings4 dim

Where ADA stands among ~20K protein-coding genes

#1,369of 20,598
Most Researched269 · top 10%
#538of 1,025
FDA-Approved Drug Targets2
#455of 5,509
Most Pathogenic Variants165 · top 10%
#12,423of 17,882
Most Constrained (LOEUF)1.18