ADGRV1

Chr 5ADARDigenic dominant

adhesion G protein-coupled receptor V1

Also known as: FEB4, GPR98, MASS1, USH2B, USH2C, VLGR1, VLGR1b

NCBI Gene: 84059ENSG00000164199UniProt: Q8WXG9

This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Febrile seizures, familial, 4MIM #604352
AD
Usher syndrome, type 2CMIM #605472
ARDigenic dominant
Usher syndrome, type 2C, GPR98/PDZD7 digenicMIM #605472
ARDigenic dominant
UniProtUsher syndrome 2C
556
ClinVar variants
51
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADGRV1
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 192 VUS of 556 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.
0.52LOEUF
pLI 0.000
Z-score 8.19
OE 0.44 (0.38–0.52)
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.
0.07Z-score
OE missense 1.00 (0.97–1.03)
3130 obs / 3141.7 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.0.44 (0.38–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.97–1.03)
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.1.02
0≤1.21.6
LoF obs/exp: 110 / 249.6Missense obs/exp: 3130 / 3141.7Syn Z: -0.55

ClinVar Variant Classifications

556 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic19
VUS192
Likely Benign301
Benign7
Conflicting5
32
Pathogenic
19
Likely Pathogenic
192
VUS
301
Likely Benign
7
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
18
0
32
Likely Pathogenic
15
0
4
0
19
VUS
0
183
8
1
192
Likely Benign
0
47
89
165
301
Benign
0
4
1
2
7
Conflicting
—5
Total29234120168556

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

View in ClinVar →

Protein Context — Lollipop Plot

ADGRV1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ADGRV1-related Usher syndrome

strong
ARLoss Of FunctionAbsent Gene Product
EyeEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Febrile seizures, familial, 4

MIM #604352

Molecular basis of disorder known

Autosomal dominant

Usher syndrome, type 2C

MIM #605472

Molecular basis of disorder known

Autosomal recessiveDigenic dominant

Usher syndrome, type 2C, GPR98/PDZD7 digenic

MIM #605472

Molecular basis of disorder known

Autosomal recessiveDigenic dominant
📖
GeneReview available — ADGRV1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
Hamann J et al.·Pharmacol Rev
2015Review
The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification.
Delmaghani S et al.·Hum Genet
2022Review
Genotypic and phenotypic characteristics of ADGRV1 mutations in four children and functional validation in a zebrafish model.
Xiao X et al.·Gene
2025Case report
Novel ADGRV1 pathogenic variant associated to sleep-related hypermotor epilepsy.
Russo A et al.·Epileptic Disord
2025Case report
Correlation between ADGRV1 expression and clinical pathological and prognostic features in breast cancer.
Wang L et al.·Sci Rep
2025
Genotype and phenotype analysis of epilepsy caused by ADGRV1 mutations in Chinese children.
Leng X et al.·Seizure
2022
Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2.
Stemerdink M et al.·Hum Genet
2022Review
Genetic etiology of non-syndromic hearing loss in Europe.
Del Castillo I et al.·Hum Genet
2022Review
Detailed Clinical, Ophthalmic, and Genetic Characterization of ADGRV1-Associated Usher Syndrome.
Daich Varela M et al.·Am J Ophthalmol
2023
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
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