ADRA2C

Chr 4

adrenoceptor alpha 2C

Also known as: ADRA2L2, ADRA2RL2, ADRARL2, ALPHA2CAR

ADRA2C encodes the alpha-2C adrenergic receptor, a G protein-coupled receptor that mediates presynaptic inhibition of neurotransmitter release from noradrenergic nerve terminals in sympathetic and central nervous systems, specifically modulating neurotransmission at lower levels of nerve activity. The gene is moderately constrained against loss-of-function variants (LOEUF 0.605), but specific disease associations and inheritance patterns for ADRA2C mutations have not been established in the current clinical literature.

Summary from RefSeq, UniProt
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0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.60
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryADRA2C
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.502
Z-score 2.41
OE 0.19 (0.080.60)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.64Z-score
OE missense 0.70 (0.610.79)
161 obs / 231.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.080.60)
00.351.4
Missense OE0.70 (0.610.79)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 2 / 10.4Missense obs/exp: 161 / 231.2Syn Z: -0.65
DN
0.6550th %ile
GOF
0.77top 25%
LOF
0.4528th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ADRA2C · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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