ADGRA1
Chr 10adhesion G protein-coupled receptor A1
Also known as: GPR123
This gene encodes an adhesion G-protein-coupled receptor that functions as an orphan receptor, with related proteins in the family regulating sensory systems, blood pressure, immune responses, and development. Mutations in ADGRA1 cause autosomal recessive bilateral frontoparietal polymicrogyria, a cortical malformation disorder affecting brain development. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance requiring biallelic mutations to cause disease.
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
236 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 | 93 | 0 | 93 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 109 | 17 | 0 | 126 |
Likely Benign | 0 | 5 | 2 | 1 | 8 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 115 | 117 | 1 | 233 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ADGRA1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools