ADGRA1

Chr 10

adhesion G protein-coupled receptor A1

Also known as: GPR123

NCBI Gene: 84435 ENSG00000197177 UniProt: Q86SQ6 OMIM: 612302

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that belongs to the adhesion family of G-protein-coupled receptors. Members of this family function in several sensory systems and regulate blood pressure, immune responses, food intake and development. A similar protein in rodents is thought to play a role in in the regulation of neuronal signaling pathways. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Mar 2014]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— ADGRA1

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ClinVar Variants

110 VUS of 120 total submissions

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Some data sources returned errors (1)

gnomad: Error: Service overloaded

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.77top 25%

GOF

0.81top 10%

LOF

0.3843th %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

120 submitted variants in ClinVar

ClinVar

Classification Summary

VUS110

Likely Benign6

Benign1

110

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	110	0	110
Likely Benign	5	1	6
Benign	1	0	1
Total	116	1	117

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

View in ClinVar →

99 pathogenic / likely-pathogenic (of 119) ClinVar copy-number / structural variants overlap ADGRA1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →