ADGRG6
protein-codingadhesion G protein-coupled receptor G6, the group of Adhesion G protein-coupled receptors, subfamily G
Gene summary
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]
- GPR126
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~144.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014670
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014670
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0001071
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0014670
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014670
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADGRG6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198569.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 16 | 2 | 21 | ||
| missense | 1 | 161 | 16 | 5 | 183 | |
| nonsense | 2 | 1 | 2 | 5 | ||
| start loss | 0 | |||||
| frameshift | 2 | 2 | 4 | |||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 4 | 6 | 167 | 32 | 7 | 216 |
Highest pathogenic variant AF is 0.0000054734987
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_940971.2 | 25 | MANE Select | |
| Ensembl | ENSP00000356581.3 | 25 | MANE Select | |
| RefSeq | NP_001027566.2 | 25 | Standard | |
| RefSeq | NP_001027567.2 | 24 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adgrg6 | Danio rerio | Structure: otic vesicle protrusion Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mitochondrion organization
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- Schwann cell differentiation
Molecular Function
- G protein-coupled receptor activity
- collagen binding
- laminin binding
- extracellular matrix binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367609
- Coding exons
- 25
- Length
- 144413
- Individuals with no LoFs
- 124609
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 53
- Defined
- 124662
- p
- 0.000213
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 538 | 622 | 0.866 | 0.0000298 | 8248 |
| Missense (PolyPhen) | 178 | 260.11 | 0.68433 | 3581 | ||
| Synonymous | 0.551 | 218 | 229 | 0.954 | 0.0000113 | 2329 |
| Loss of Function | 4.87 | 19 | 59.6 | 0.319 | 0.00000300 | 771 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00024 | 0.00022 | rare |
| Finnish | 0.00019 | 0.00019 | rare |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0.00015 | 0.00013 | rare |
| Other | 0.00050 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane (By similarity). Couples to G(i)-proteins as well as G(s)-proteins (PubMed:24227709). Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:24227709). Regulates neural, cardiac and ear development via G-protein- and/or N-terminus-dependent signaling (By similarity). May act as a receptor for PRNP which may promote myelin homeostasis (By similarity). {ECO:0000250|UniProtKB:C6KFA3, ECO:0000269|PubMed:24227709, ECO:0000269|PubMed:26004201}.;
- Disease
- DISEASE: Lethal congenital contracture syndrome 9 (LCCS9) [MIM:616503]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:26004201}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- RVIS EVS
- -0.17
- RVIS percentile EVS
- 40.68
Essentials
- Essential (gene trap)
- N