ADGRG6

Chr 6AR

adhesion G protein-coupled receptor G6

Also known as: APG1, DREG, GPR126, LCCS9, PR126, PS1TP2, VIGR

The protein is an adhesion G-protein coupled receptor that binds steroid hormones like progesterone and signals through G proteins to regulate adenylate cyclase, playing roles in peripheral nervous system myelination, blood-brain barrier formation, and bone development. Mutations cause autosomal recessive polymicrogyria, megalencephaly, and hydrocephalus (PMGYSH), affecting brain development and structure. This gene is highly constrained against loss-of-function variants (LOEUF 0.468), indicating that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.471 OMIM phenotype
Clinical SummaryADGRG6
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.000
Z-score 4.87
OE 0.32 (0.220.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.19Z-score
OE missense 0.87 (0.810.93)
538 obs / 621.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.220.47)
00.351.4
Missense OE0.87 (0.810.93)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 19 / 59.6Missense obs/exp: 538 / 621.6Syn Z: 0.55
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveADGRG6-related lethal congenital contracture syndromeLOFAR

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

DN
0.76top 25%
GOF
0.7029th %ile
LOF
0.2678th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ADGRG6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →