ADARB1

Chr 21

adenosine deaminase RNA specific B1

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

NCBI Gene: 104 ENSG00000197381 UniProt: P78563

ADARB1 encodes an adenosine deaminase that catalyzes A-to-I RNA editing in double-stranded RNA, modifying the amino acid sequences of important neurotransmitter receptors including glutamate, serotonin, and GABA receptors. Biallelic mutations cause a neurodevelopmental disorder with hypotonia, microcephaly, and seizures, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.399), indicating that haploinsufficiency is likely not tolerated in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.40

Clinical Summary— ADARB1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 72 VUS of 114 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

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?

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?

LoF OE?0.17 (0.09–0.40)

0≤0.351.4

Missense OE?0.53 (0.48–0.59)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 4 / 23.0Missense obs/exp: 242 / 452.6Syn Z: 0.60

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedADARB1-related microcephaly, intellectual disability, and seizuresOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4388th %ile

GOF

0.3193th %ile

LOF

0.71top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

VUS72

Likely Benign16

Benign6

Conflicting1

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	5	0	0	6
Likely Pathogenic	0	0	0	0	0
VUS	3	66	3	0	72
Likely Benign	0	2	4	10	16
Benign	0	2	0	4	6
Conflicting	—				1
Total	4	75	7	14	101

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

View in ClinVar →

91 pathogenic / likely-pathogenic (of 120) ClinVar copy-number / structural variants overlap ADARB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →