ADA2

Chr 22AR

adenosine deaminase 2

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

NCBI Gene: 51816 ENSG00000093072 UniProt: Q9NZK5 OMIM: 607575

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Sneddon syndromeMIM #182410

Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndromeMIM #615688

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · obsolete deficiency of adenosine deaminase 2 · AR · ClinGen 2023

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.07

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in ADA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

678 rare PASS variants

Rare truncating (LoF)

1 in 710

92 rare PASS variants

Rare synonymous (reference)

1 in 230

230 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADA2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 640
South Asian	~43k	1 in 70	1 in 880
Remaining (unassigned)	~30k	1 in 61	1 in 1,300
European (Finnish)	~27k	1 in 210	1 in 2,200
Admixed American	~22k	1 in 70	1 in 410
African / African American	~21k	1 in 93	1 in 1,200
East Asian	~20k	1 in 92	1 in 1,200
Ashkenazi Jewish	~13k	1 in 400	none seen
Middle Eastern	~2,884	1 in 89	1 in 570

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓