ADGRV1

adhesion G protein-coupled receptor V1, the group of USH2 complex |Adhesion G protein-coupled receptors, subfamily V

Basic information

Region (hg38): 5:90529343-91164437

Previous symbols: [ "USH2C", "MASS1", "GPR98" ]

Links

ENSG00000164199 ∙ NCBI:84059 ∙ OMIM:602851 ∙ HGNC:17416 ∙ Uniprot:Q8WXG9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Usher syndrome type 2C (Strong), mode of inheritance: AR
• febrile seizures, familial, 4 (Limited), mode of inheritance: AD
• Usher syndrome type 2 (Supportive), mode of inheritance: AR
• Usher syndrome type 2C (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Disputed Evidence), mode of inheritance: AR
• Usher syndrome type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Usher syndrome, type IIC	AR/Digenic	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	12402266; 14740321; 16273391;19357116; 18854872; 0440071; 21174530
Digenic inheritance has been described (with PDZD7)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADGRV1 gene.

• not provided (4464 variants)
• not specified (541 variants)
• Usher syndrome type 2C (471 variants)
• Inborn genetic diseases (247 variants)
• Febrile seizures, familial, 4;Usher syndrome type 2C (50 variants)
• Usher syndrome type 2C;Febrile seizures, familial, 4 (46 variants)
• Retinal dystrophy (40 variants)
• Usher syndrome (31 variants)
• Febrile seizures, familial, 4 (30 variants)
• Rare genetic deafness (24 variants)
• ADGRV1-related condition (22 variants)
• Hearing impairment (18 variants)
• Usher syndrome type 2 (8 variants)
• Seizure (5 variants)
• Retinitis pigmentosa (4 variants)
• Idiopathic generalized epilepsy (3 variants)
• Febrile seizures, familial, 1 (3 variants)
• Meniere disease (2 variants)
• ADGRV1-Related Disorders (2 variants)
• Beta-D-mannosidosis (1 variants)
• Hearing loss, autosomal recessive (1 variants)
• See cases (1 variants)
• Autosomal recessive sensorineural hearing loss (1 variants)
• Abnormal activity of mitochondrial respiratory chain (1 variants)
• ADGRV1-related myoclonic epilepsy (1 variants)
• Ear malformation (1 variants)
• Usher syndrome type 1 (1 variants)
• Cerebral arteriovenous malformation;Arteriovenous malformation;Hand tremor;Tremor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADGRV1 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			32	843	28	903
missense	3	9	1756	227	51	2046
nonsense	100	21	1			122
start loss		1				1
frameshift	169	30	5			204
inframe indel			14			14
splice donor/acceptor (+/-2bp)	17	50	4		1	72
splice region		1	84	108	10	203
non coding		1	31	499	257	788
Total	289	112	1843	1569	337

Highest pathogenic variant AF is 0.0000460

Variants in ADGRV1

This is a list of pathogenic ClinVar variants found in the ADGRV1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-90558495-C-G			Benign (Jul 07, 2018)
5-90558508-A-G			Benign (Jun 14, 2018)
5-90558610-C-T			Likely benign (Dec 21, 2018)
5-90558631-G-C			Benign (Jun 14, 2018)
5-90558666-G-A			Benign (Aug 13, 2018)
5-90558750-G-A			Likely benign (Dec 31, 2018)
5-90558798-G-A		not specified • Usher syndrome type 2C	Benign (Aug 07, 2018)
5-90558829-A-T		Usher syndrome type 2C	Likely benign (Aug 23, 2018)
5-90558849-G-C		Usher syndrome type 2C	Benign (Apr 10, 2018)
5-90558852-C-T		not specified • Usher syndrome type 2C	Conflicting classifications of pathogenicity (Jan 13, 2018)
5-90558869-CCGGCGGGGACCGCCGGGA-C		not specified • ADGRV1-related disorder	Conflicting classifications of pathogenicity (Jul 31, 2020)
5-90558885-G-A		not specified	Uncertain significance (Apr 10, 2013)
5-90558896-A-T			Uncertain significance (Dec 22, 2022)
5-90558898-G-A			Likely pathogenic (Dec 08, 2022)
5-90558901-G-C			Likely benign (Jun 14, 2023)
5-90558901-G-T			Likely benign (Oct 16, 2023)
5-90558908-C-T			Likely benign (Jan 07, 2024)
5-90558910-G-C		not specified	Likely benign (Sep 14, 2017)
5-90558913-G-T			Likely benign (Nov 24, 2023)
5-90558916-A-C		not specified	Conflicting classifications of pathogenicity (Aug 20, 2022)
5-90558920-A-C			Uncertain significance (May 08, 2022)
5-90558923-C-T			Uncertain significance (Aug 25, 2021)
5-90558925-A-G			Likely benign (Nov 05, 2023)
5-90558926-T-C		not specified • ADGRV1-related disorder	Benign/Likely benign (Jan 31, 2024)
5-90558929-C-A			Likely benign (Oct 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADGRV1	protein_coding	protein_coding	ENST00000405460	90	634878

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.17e-39	1.00	124366	0	313	124679	0.00126

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0740	3130	3.14e+3	0.996	0.000160	41060
Missense in Polyphen		852	944.78	0.9018		12042
Synonymous	-0.554	1179	1.16e+3	1.02	0.0000632	12548
Loss of Function	8.19	110	250	0.441	0.0000132	3267

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00229	0.00228
Ashkenazi Jewish	0.00	0.00
East Asian	0.00137	0.00134
Finnish	0.000607	0.000603
European (Non-Finnish)	0.00142	0.00138
Middle Eastern	0.00137	0.00134
South Asian	0.00191	0.00183
Other	0.00169	0.00165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor that may have an important role in the development of the central nervous system.
• Disease: DISEASE: Usher syndrome 2C (USH2C) [MIM:605472]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269|PubMed:14740321, ECO:0000269|PubMed:22147658}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Febrile seizures, familial, 4 (FEB4) [MIM:604352]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: GPCRs, Other (Consensus)

Recessive Scores

• pRec: 0.170

Intolerance Scores

• rvis_EVS: 8.12
• rvis_percentile_EVS: 99.95

Haploinsufficiency Scores

• pHI: 0.0774
• hipred: N
• hipred_score: 0.426
• ghis: 0.417

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Adgrv1
• Phenotype: hearing/vestibular/ear 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); vision/eye 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)