ADGRG6

adhesion G protein-coupled receptor G6, the group of Adhesion G protein-coupled receptors, subfamily G

Basic information

Region (hg38): 6:142301854-142446266

Previous symbols: [ "GPR126" ]

Links

ENSG00000112414 ∙ NCBI:57211 ∙ OMIM:612243 ∙ HGNC:13841 ∙ Uniprot:Q86SQ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lethal congenital contracture syndrome 9 (Definitive), mode of inheritance: AR
• lethal congenital contracture syndrome 9 (Moderate), mode of inheritance: AR
• lethal congenital contracture syndrome 9 (Strong), mode of inheritance: AR
• intellectual disability (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lethal congenital contracture syndrome 9	AR	General	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	Craniofacial; Musculoskeletal; Neurologic	26004201

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADGRG6 gene.

• Lethal congenital contracture syndrome 9 (4 variants)
• Arthrogryposis multiplex congenita (3 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADGRG6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				12	4	16
missense	1		72	7	8	88
nonsense	2					2
start loss						0
frameshift	2	1				3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	2	2	5
non coding			3	3	27	33
Total	5	2	76	22	39

Variants in ADGRG6

This is a list of pathogenic ClinVar variants found in the ADGRG6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-142301906-T-C			Benign (May 25, 2021)
6-142302016-T-G			Benign (May 25, 2021)
6-142302064-C-T			Benign (May 24, 2021)
6-142302089-G-A			Benign (May 25, 2021)
6-142302091-C-T			Benign (May 12, 2021)
6-142302510-A-G			Benign (May 20, 2021)
6-142309521-A-G			Benign (May 12, 2021)
6-142309560-C-T		Arthrogryposis multiplex congenita • Lethal congenital contracture syndrome 9	Pathogenic (Dec 01, 2014)
6-142309575-C-T		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
6-142309603-T-C		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
6-142309626-A-G		Inborn genetic diseases	Likely benign (Jun 18, 2021)
6-142367613-G-A			Uncertain significance (Mar 23, 2020)
6-142367667-A-G		Inborn genetic diseases • ADGRG6-related disorder	Conflicting classifications of pathogenicity (Mar 29, 2022)
6-142367674-C-T			Benign (Dec 31, 2019)
6-142367680-G-A			Uncertain significance (Oct 14, 2019)
6-142367690-C-T			Benign (May 04, 2021)
6-142367704-A-G		Inborn genetic diseases	Uncertain significance (Jul 22, 2022)
6-142367770-A-C		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
6-142367770-A-G			Uncertain significance (Oct 14, 2019)
6-142367797-G-A		Inborn genetic diseases	Uncertain significance (May 04, 2022)
6-142367819-A-G		Lethal congenital contracture syndrome 9	Benign/Likely benign (Sep 01, 2023)
6-142367832-A-G			Benign (May 04, 2021)
6-142367905-T-A			Benign (May 04, 2021)
6-142370175-G-A		Inborn genetic diseases	Uncertain significance (May 05, 2023)
6-142370231-A-G			Likely benign (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADGRG6	protein_coding	protein_coding	ENST00000367609	25	144413

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000661	1.00	124609	0	53	124662	0.000213

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	538	622	0.866	0.0000298	8248
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000279	0.000278
Ashkenazi Jewish	0.0000995	0.0000994
East Asian	0.000241	0.000223
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000272	0.000265
Middle Eastern	0.000241	0.000223
South Asian	0.000145	0.000131
Other	0.000499	0.000496

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.0882
• hipred: N
• hipred_score: 0.491
• ghis: 0.516

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Adgrg6
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: adgrg6
• Affected structure: otic vesicle protrusion
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• 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;cAMP-mediated signaling;myelination in peripheral nervous system;myelination;heart trabecula formation
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane
• Molecular function: G protein-coupled receptor activity;collagen binding;laminin binding;extracellular matrix binding