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…

LOFmechanismAR/ADLOEUF 0.422 OMIM phenotypes

Clinical Summary— ADAR

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

64 unique Pathogenic / Likely Pathogenic· 584 VUS of 1085 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveADAR-related dyschromatosis symmetrica hereditariaLOFAD

definitiveADAR-related Aicardi-Goutieres syndrome associated with a type I interferon signatureOTHERAD

definitiveADAR-related Aicardi-Goutieres syndrome associated with a type I interferon signatureLOFAR

This gene — mechanism propensity

0.5771th %ile

GOF

0.4875th %ile

LOF

0.4627th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · 89% of P/LP variants are LoF · LOEUF 0.42

DN1 literature citation

Literature Evidence

DNThe proximity of Gly1007 to the RNA backbone, and the possibility for an arginine residue to make polyvalent interactions there, suggests a mechanism whereby Arg1007 might confer a dominant-negative effect: by binding more tightly to RNA, the mutant protein could act as a competitive inhibitor of wi1

LOFTwo novel mutations and evidence for haploinsufficiency of the ADAR gene in dyschromatosis symmetrica hereditaria.2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

ClinVar Variant Classifications

1085 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41

Likely Pathogenic23

VUS584

Likely Benign396

Benign7

Conflicting11

Pathogenic

Likely Pathogenic

584

VUS

396

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	38	3	0	0	41
Likely Pathogenic	19	4	0	0	23
VUS	5	537	34	8	584
Likely Benign	0	2	142	252	396
Benign	0	1	5	1	7
Conflicting	—				11
Total	62	547	181	261	1,062

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap ADAR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →