ADGRG1

Chr 16AR

adhesion G protein-coupled receptor G1

Also known as: BFPP, BPPR, CDCBM14B, CDCBM15A, GPR56, TM7LN4, TM7XN1

NCBI Gene: 9289ENSG00000205336UniProt: Q9Y653

This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Primary Disease Associations & Inheritance

Cortical dysplasia, complex, with other brain malformations 14A, (bilateral frontoparietal)MIM #606854
AR
Cortical dysplasia, complex, with other brain malformations 14B, (bilateral perisylvian)MIM #615752
1146
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADGRG1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1146 total variants — no pathogenic classifications of 1146 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.000
Z-score 2.07
OE 0.61 (0.43–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.07Z-score
OE missense 1.01 (0.93–1.10)
390 obs / 386.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.43–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.93–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 20 / 32.8Missense obs/exp: 390 / 386.2Syn Z: -1.15

ClinVar Variant Classifications

1146 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

ADGRG1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ADGRG1-related polymicrogyria

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cortical dysplasia, complex, with other brain malformations 14A, (bilateral frontoparietal)

MIM #606854

Molecular basis of disorder known

Autosomal recessive

Cortical dysplasia, complex, with other brain malformations 14B, (bilateral perisylvian)

MIM #615752

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
Hamann J et al.·Pharmacol Rev
2015Review
Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers.
Zheng C et al.·Cancer Cell
2022
Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings.
Kuo CY et al.·Epilepsia Open
2023Review
Demarcating the Development of Cirrhosis and Its Complications via Plasma Proteomic Features in an Asymptomatic Population.
Liang Z et al.·J Proteome Res
2025
Update on preclinical and clinical efforts on ex-vivo expansion of hematopoietic stem and progenitor cells.
Huang X et al.·Curr Opin Hematol
2022Review
Microglial ADGRG1: AD glial resilience generator.
Barclay KM et al.·Neuron
2025
A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer.
Lei P et al.·Int Immunopharmacol
2022
A specific GPR56/ADGRG1 splicing isoform is associated with antidepressant response in major depressive disorder.
Lion M et al.·Eur Neuropsychopharmacol
2025
PLAG1 fusions define a third subtype of CNS embryonal tumor with PLAG family gene alteration.
Keck MK et al.·Acta Neuropathol
2025
Pathophysiological impact of the adhesion G protein-coupled receptor family.
Einspahr JM et al.·Am J Physiol Cell Physiol
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools