ADA2

Chr 22

adenosine deaminase 2

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

NCBI Gene: 51816 ENSG00000093072 UniProt: Q9NZK5

The protein is a secreted adenosine deaminase that degrades extracellular adenosine and regulates cell proliferation and differentiation. Biallelic mutations cause vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome and Sneddon syndrome, both inherited in an autosomal recessive pattern. The gene is highly intolerant to loss-of-function variants, reflecting its critical role in immune and vascular function.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.07

Clinical Summary— ADA2

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Gene-Disease Validity (ClinGen)

obsolete deficiency of adenosine deaminase 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.36Z-score

OE missense 0.94 (0.85–1.04)

280 obs / 297.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.45–1.07)

0≤0.351.4

Missense OE?0.94 (0.85–1.04)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 14 / 20.5Missense obs/exp: 280 / 297.3Syn Z: 0.37

This gene — mechanism propensity

0.7325th %ile

GOF

0.6052th %ile

LOF

0.2387th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.