ADRA2C
Chr 4adrenoceptor 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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
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
199 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 115 | 0 | 115 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 68 | 2 | 0 | 70 |
Likely Benign | 0 | 0 | 1 | 5 | 6 |
Benign | 0 | 2 | 0 | 2 | 4 |
| Total | 0 | 70 | 122 | 7 | 199 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools