ADAR

Chr 1ARAD

adenosine deaminase RNA specific

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

NCBI Gene: 103ENSG00000160710UniProt: P55265

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]

Primary Disease Associations & Inheritance

Aicardi-Goutieres syndrome 6MIM #615010
AR
Dyschromatosis symmetrica hereditariaMIM #127400
AD
577
ClinVar variants
49
Pathogenic / LP
0.03
pLI score
2
Active trials
Clinical Summary— ADAR
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 320 VUS of 577 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
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?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.
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?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.0.26 (0.17–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.70–0.81)
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.1.13
0≤1.21.6
LoF obs/exp: 13 / 49.2Missense obs/exp: 502 / 667.1Syn Z: -1.62

ClinVar Variant Classifications

577 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic15
VUS320
Likely Benign202
Benign5
Conflicting1
34
Pathogenic
15
Likely Pathogenic
320
VUS
202
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
4
13
0
34
Likely Pathogenic
10
2
3
0
15
VUS
4
288
21
7
320
Likely Benign
0
0
69
133
202
Benign
0
1
4
0
5
Conflicting
—1
Total31295110140577

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAR · protein map & ClinVar variants

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

Gene2Phenotype Curations

ADAR-related dyschromatosis symmetrica hereditaria

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

ADAR-related Aicardi-Goutieres syndrome associated with a type I interferon signature

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

ADAR-related Aicardi-Goutieres syndrome associated with a type I interferon signature

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Aicardi-Goutieres syndrome 6

MIM #615010

Molecular basis of disorder known

Autosomal recessive

Dyschromatosis symmetrica hereditaria

MIM #127400

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ADAR
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RNA editing: Expanding the potential of RNA therapeutics.
Booth BJ et al.·Mol Ther
2023Review
Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides.
Merkle T et al.·Nat Biotechnol
2019
Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.
Crow YJ et al.·Am J Med Genet A
2015
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.
Rice GI et al.·Lancet Neurol
2013
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer.
Umeda H et al.·Mol Cancer
2025
Emerging clinical applications of ADAR based RNA editing.
Rainaldi J et al.·Stem Cells Transl Med
2025Review
Systemic complications of Aicardi Goutières syndrome using real-world data.
Peixoto de Barcelos I et al.·Mol Genet Metab
2024
Advances in A-to-I RNA editing in cancer.
Zhang Y et al.·Mol Cancer
2024Review
A loss-of-function human ADAR variant activates innate immune response and promotes bowel inflammation.
Xu P et al.·Nat Commun
2025
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
Rectum Cancer, Adenocarcinoma

ADAR1 Expression Level in Rectal Cancer

RECRUITING
NCT07108348Necmettin Erbakan UniversityStarted 2025-06-01
Adenosine deaminase acting on RNA1
Non-Muscle Invasive Bladder Urothelial CarcinomaRecurrent Non-Muscle Invasive Bladder Urothelial Carcinoma

Study to Determine Possible Effects of Apalutamide, Compared to Placebo, on EGFR Expression in Patients With Non-muscle Invasive Bladder Cancer

NOT YET RECRUITING
NCT05521698Phase PHASE1University of Wisconsin, MadisonStarted 2026-04
ApalutamideBiopsy ProcedureBiospecimen Collection

External Resources

Links to major genomics databases and tools