ADAR

Chr 1ARAD

adenosine deaminase RNA specific

Also known as: ADAR1, AGS6, DRADA, DSH, DSRAD, G1P1, IFI-4, IFI4

NCBI Gene: 103 ENSG00000160710 UniProt: P55265 OMIM: 146920

This gene encodes an enzyme that catalyzes adenosine-to-inosine RNA editing in double-stranded RNA, which can alter protein sequences, RNA splicing, and RNA stability. Mutations cause Aicardi-Goutières syndrome 6, a severe early-onset encephalopathy with neuroinflammation, and dyschromatosis symmetrica hereditaria, a skin pigmentation disorder. The gene shows both autosomal recessive and autosomal dominant inheritance patterns depending on the associated phenotype.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Aicardi-Goutieres syndrome 6MIM #615010

Dyschromatosis symmetrica hereditariaMIM #127400

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

200

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ADAR

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.026

Z-score 4.78

OE 0.26 (0.17–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.27Z-score

OE missense 0.75 (0.70–0.81)

502 obs / 667.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.17–0.42)

0≤0.351.4

Missense OE?0.75 (0.70–0.81)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 13 / 49.2Missense obs/exp: 502 / 667.1Syn Z: -1.62

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

1,329 rare PASS variants

Rare truncating (LoF)

1 in 2,600

124 rare PASS variants

Rare synonymous (reference)

1 in 99

651 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADAR. 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 97	1 in 2,300
South Asian	~43k	1 in 43	1 in 1,500
Remaining (unassigned)	~30k	1 in 75	1 in 3,800
European (Finnish)	~27k	1 in 190	≈ 1 in 8,800
Admixed American	~22k	1 in 67	1 in 2,800
African / African American	~21k	1 in 56	1 in 1,700
East Asian	~20k	1 in 58	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 41	≈ 1 in 2,900

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 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓