ADGRV1

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

Basic information

Region (hg38): 5:90529344-91164437

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
Usher syndrome type 2C (Strong), 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 (5934 variants)
Inborn_genetic_diseases (715 variants)
not_specified (585 variants)
Usher_syndrome_type_2C (581 variants)
Febrile_seizures,_familial,_4 (205 variants)
ADGRV1-related_disorder (182 variants)
Retinal_dystrophy (84 variants)
Usher_syndrome (44 variants)
Usher_syndrome_type_2 (33 variants)
Rare_genetic_deafness (25 variants)
Hearing_impairment (19 variants)
Retinitis_pigmentosa (6 variants)
Idiopathic_generalized_epilepsy (6 variants)
Usher_syndrome_type_2A (4 variants)
Intellectual_disability (3 variants)
Craniosynostosis_syndrome (3 variants)
Optic_atrophy (3 variants)
Febrile_seizures,_familial,_1 (3 variants)
Meniere_disease (2 variants)
Usher_syndrome_type_1 (2 variants)
Beta-D-mannosidosis (1 variants)
Autosomal_recessive_sensorineural_hearing_loss (1 variants)
Hearing_loss,_autosomal_recessive (1 variants)
Ear_malformation (1 variants)
ADGRV1-related_myoclonic_epilepsy (1 variants)
Arteriovenous_malformation (1 variants)
Hand_tremor (1 variants)
Tremor (1 variants)
Usher_syndrome,_type_IIC,_GPR98/PDZD7_digenic (1 variants)
Abnormal_activity_of_mitochondrial_respiratory_chain (1 variants)
See_cases (1 variants)
Vascular_disorder (1 variants)
Monogenic_hearing_loss (1 variants)
Cerebral_arteriovenous_malformation (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. These statistics are base on transcript: NM_000032119.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	25 clinvar	1700 clinvar	29 clinvar	1756
missense	11 clinvar	25 clinvar	1820 clinvar	1055 clinvar	62 clinvar	2973
nonsense	150 clinvar	44 clinvar				194
start loss		1	1			2
frameshift	248 clinvar	58 clinvar	7 clinvar			313
splice donor/acceptor (+/-2bp)	20 clinvar	82 clinvar	4 clinvar	1 clinvar		107
Total	430	211	1857	2756	91

Highest pathogenic variant AF is 0.0000770222

Loading clinvar variants...

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

loftool
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_CRISPR
essential_gene_CRISPR2
essential_gene_gene_trap: N
gene_indispensability_pred
gene_indispensability_score

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);