ADARB1

Chr 21AR

adenosine deaminase RNA specific B1

Also known as: ADAR2, DRABA2, DRADA2, NEDHYMS, RED1

NCBI Gene: 104ENSG00000197381UniProt: P78563

This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rat found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, microcephaly, and seizuresMIM #618862
AR
218
ClinVar variants
97
Pathogenic / LP
0.80
pLI score
0
Active trials
Clinical Summary— ADARB1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 95 VUS of 218 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
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.
0.40LOEUF
pLI 0.803
Z-score 3.67
OE 0.17 (0.09–0.40)
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.
3.52Z-score
OE missense 0.53 (0.48–0.59)
242 obs / 452.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.17 (0.09–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.48–0.59)
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.0.94
0≤1.21.6
LoF obs/exp: 4 / 23.0Missense obs/exp: 242 / 452.6Syn Z: 0.60

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic4
VUS95
Likely Benign18
Benign6
Conflicting2
93
Pathogenic
4
Likely Pathogenic
95
VUS
18
Likely Benign
6
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
5
87
0
93
Likely Pathogenic
0
0
4
0
4
VUS
2
64
29
0
95
Likely Benign
0
2
7
9
18
Benign
0
2
0
4
6
Conflicting
—2
Total37312713218

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

View in ClinVar →

Protein Context — Lollipop Plot

ADARB1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ADARB1-related microcephaly, intellectual disability, and seizures

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia, microcephaly, and seizures

MIM #618862

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nanocarriers Targeting Circular RNA ADARB1 Boost Radiosensitivity of Nasopharyngeal Carcinoma through Synergically Promoting Ferroptosis.
Wang D et al.·ACS Nano
2024
Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures.
Tan TY et al.·Am J Hum Genet
2020
C to U RNA editing of MFN1 is regulated by ADARB1 and associates with favourable prognosis in chronic lymphocytic leukemia.
Gonzalez Martinez A et al.·Sci Rep
2025
Function of low ADARB1 expression in lung adenocarcinoma.
Wang X et al.·PLoS One
2019
Role of downregulated ADARB1 in lung squamous cell carcinoma.
Wang X et al.·Mol Med Rep
2020
Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients.
Karanović J et al.·J Neural Transm (Vienna)
2017Cohort
Routine Diagnostics Confirm Novel Neurodevelopmental Disorders.
Jauss RT et al.·Genes (Basel)
2022
Variants in TPH2 and ADARB1 genes in completed suicide from the Slovenian population - a follow-up to findings on attempted suicide in the Serbian population.
Karanović J et al.·World J Biol Psychiatry
2026Natural history
ADARB1 inhibits glycolysis and progression of cervical cancer through the HMGB1/PFKFB3 axis.
Liu X et al.·Biochim Biophys Acta Mol Basis Dis
2026
Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy.
Maroofian R et al.·J Med Genet
2021Case report
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools