ADA2

Chr 22AR

adenosine deaminase 2

Also known as: ADGF, CECR1, IDGFL, PAN, SNEDS, VAIHS

NCBI Gene: 51816ENSG00000093072UniProt: Q9NZK5

This gene encodes a member of a subfamily of the adenosine deaminase protein family. The encoded protein is one of two adenosine deaminases found in humans, which regulate levels of the signaling molecule, adenosine. The encoded protein is secreted from monocytes undergoing differentiation and may regulate cell proliferation and differentiation. This gene may be responsible for some of the phenotypic features associated with cat eye syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Primary Disease Associations & Inheritance

Sneddon syndromeMIM #182410
AR
Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndromeMIM #615688
AR
703
ClinVar variants
76
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ADA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 195 VUS of 703 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.07LOEUF
pLI 0.000
Z-score 1.32
OE 0.68 (0.45–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.36Z-score
OE missense 0.94 (0.85–1.04)
280 obs / 297.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.45–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.85–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 14 / 20.5Missense obs/exp: 280 / 297.3Syn Z: 0.37

ClinVar Variant Classifications

703 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic30
VUS195
Likely Benign171
Benign33
Conflicting14
46
Pathogenic
30
Likely Pathogenic
195
VUS
171
Likely Benign
33
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
6
27
0
46
Likely Pathogenic
14
10
5
1
30
VUS
2
164
25
4
195
Likely Benign
0
1
79
91
171
Benign
0
0
32
1
33
Conflicting
—14
Total2918116897489

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ADA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Sneddon syndrome

MIM #182410

Molecular basis of disorder known

Autosomal recessive

Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome

MIM #615688

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deficiency of adenosine deaminase 2 (DADA2): Review.
Sharma V et al.·Best Pract Res Clin Rheumatol
2023Review
The Genetic Landscape of Diamond-Blackfan Anemia.
Ulirsch JC et al.·Am J Hum Genet
2018
Getting to know adenosine deaminase 2 deficiency inside and out.
Ehlers L et al.·J Allergy Clin Immunol
2025Review
Early-onset stroke and vasculopathy associated with mutations in ADA2.
Zhou Q et al.·N Engl J Med
2014
Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment.
Meyts I et al.·J Clin Immunol
2018Review
Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M et al.·Front Immunol
2021
[Polyarteritis nodosa].
Ghrenassia É et al.·Rev Prat
2025Review
A Cohort Study on Deficiency of ADA2 from China.
Li GM et al.·J Clin Immunol
2023Cohort
Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers.
Wouters M et al.·J Exp Med
2025
Systematic Review of Cerebral Phenotypes Associated With Monogenic Cerebral Small-Vessel Disease.
Whittaker E et al.·J Am Heart Assoc
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Lymphoma Diffuse Large B-cellLeukemia and LymphomaLeukemia Relapse

Study of Allo-QuadCAR01-T, an Allogeneic CAR-T Targeting CD19/CD20, in Patients With Relapsed or Refractory B-Cell Malignancies

RECRUITING
NCT07284433Phase PHASE1, PHASE2AvenCell Therapeutics, Inc.Started 2026-01-06
Cyclophosphamide (Non-IMP, Lymphodepletion)Fludarabine (Non-IMP, Lymphodepletion)Allo-QuadCAR01-T

External Resources

Links to major genomics databases and tools