ADGRG6

Chr 6AR

adhesion G protein-coupled receptor G6

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

NCBI Gene: 57211ENSG00000112414UniProt: Q86SQ4

This gene, which is upregulated in human umbilical vein endothelial cells, encodes a G protein-coupled receptor. Variations in this gene can affect a person's stature. Multiple transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Lethal congenital contracture syndrome 9MIM #616503
AR
259
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADGRG6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 158 VUS of 259 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.47LOEUF
pLI 0.000
Z-score 4.87
OE 0.32 (0.22–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.19Z-score
OE missense 0.87 (0.81–0.93)
538 obs / 621.6 exp
Tolerant

Mild missense constraint

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.0.32 (0.22–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.81–0.93)
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.0.95
0≤1.21.6
LoF obs/exp: 19 / 59.6Missense obs/exp: 538 / 621.6Syn Z: 0.55

ClinVar Variant Classifications

259 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic5
VUS158
Likely Benign34
Benign44
Conflicting2
16
Pathogenic
5
Likely Pathogenic
158
VUS
34
Likely Benign
44
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
14
0
16
Likely Pathogenic
2
1
2
0
5
VUS
0
148
10
0
158
Likely Benign
0
14
7
13
34
Benign
0
8
32
4
44
Conflicting
—2
Total41716517259

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

View 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.

Gene2Phenotype Curations

ADGRG6-related lethal congenital contracture syndrome

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

Lethal congenital contracture syndrome 9

MIM #616503

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita.
Laquerriere A et al.·J Med Genet
2022
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
Hamann J et al.·Pharmacol Rev
2015Review
Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.
Wang L et al.·Proc Natl Acad Sci U S A
2025
ADGRG6-related disorder: a novel mutation resulting in distal arthrogryposis and a patchy neuropathy.
Perrain V et al.·Neuromuscul Disord
2025Case report
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
Pan-cancer analysis identifies adhesion G protein-coupled receptor G6 as a potential prognostic and immunotherapeutic biomarker with its functional validation.
Zhu J et al.·Int J Biol Macromol
2025Functional
Heritability and genome-wide association study of diffusing capacity of the lung.
Terzikhan N et al.·Eur Respir J
2018Meta-analysis
Detection of the ADGRG6 hotspot mutations in urine for bladder cancer early screening by ARMS-qPCR.
Tan D et al.·Cancer Med
2023
Noncoding SNP at rs1663689 represses ADGRG6 via interchromosomal interaction and reduces lung cancer progression.
Lei X et al.·EMBO Rep
2023
Regulation of body length and bone mass by Gpr126/Adgrg6.
Sun P et al.·Sci Adv
2020
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