ADRA2B

Chr 2

adrenoceptor alpha 2B

Also known as: ADRA2L1, ADRA2RL1, ADRARL1, ALPHA2BAR, FAME2, alpha-2BAR

NCBI Gene: 151 ENSG00000274286 UniProt: P18089 OMIM: 104260

The alpha-2B adrenergic receptor is a G protein-coupled receptor that inhibits adenylyl cyclase and regulates neurotransmitter release from sympathetic and central adrenergic neurons, controlling blood pressure, lipolysis, and insulin release. Mutations cause autosomal dominant developmental and epileptic encephalopathy with movement abnormalities. This gene is not highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. [provided by RefSeq, Apr 2014]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.22

Clinical Summary— ADRA2B

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Gene-Disease Validity (ClinGen)

epilepsy · ADRefuted

Refuted — evidence has disproved this relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.97

OE 0.72 (0.44–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.94 (0.85–1.04)

270 obs / 287.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.44–1.22)

0≤0.351.4

Missense OE?0.94 (0.85–1.04)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 10 / 13.9Missense obs/exp: 270 / 287.4Syn Z: 1.07

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedADRA2B-related intellectual developmental disorderOTHERAR

This gene — mechanism propensity

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

0.75top 25%

GOF

0.82top 10%

LOF

0.2873th %ile

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.