ADGRG1

Chr 16AR

adhesion G protein-coupled receptor G1

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

NCBI Gene: 9289 ENSG00000205336 UniProt: Q9Y653 OMIM: 604110

ADGRG1 encodes an adhesion G-protein coupled receptor that regulates cortical development by maintaining pial basement membrane integrity and controlling neuronal migration through RhoA pathway signaling. Mutations cause autosomal recessive bilateral frontoparietal or perisylvian polymicrogyria, representing complex cortical dysplasias with other brain malformations. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.892 OMIM phenotypes

Clinical Summary— ADGRG1

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Gene-Disease Validity (ClinGen)

bilateral frontoparietal polymicrogyria · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

132 unique Pathogenic / Likely Pathogenic· 283 VUS of 1129 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 2.07

OE 0.61 (0.43–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.07Z-score

OE missense 1.01 (0.93–1.10)

390 obs / 386.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.43–0.89)

0≤0.351.4

Missense OE?1.01 (0.93–1.10)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 20 / 32.8Missense obs/exp: 390 / 386.2Syn Z: -1.15

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveADGRG1-related polymicrogyriaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.7030th %ile

LOF

0.2580th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

1129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60

Likely Pathogenic72

VUS283

Likely Benign547

Benign81

Conflicting62

Pathogenic

Likely Pathogenic

283

VUS

547

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	54	3	3	0	60
Likely Pathogenic	52	14	6	0	72
VUS	6	221	48	8	283
Likely Benign	3	15	210	319	547
Benign	0	2	75	4	81
Conflicting	—				62
Total	115	255	342	331	1,105

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap ADGRG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →