VIPR1

Chr 3

vasoactive intestinal peptide receptor 1

Also known as: HVR1, II, PACAP-R-2, PACAP-R2, RDC1, V1RG, VAPC1, VIP-R-1

NCBI Gene: 7433ENSG00000114812UniProt: P32241OMIM: 192321

The protein is a G protein-coupled receptor that binds vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), activating cAMP-dependent signaling pathways that regulate smooth muscle relaxation, hormone secretion, and epithelial ion transport. VIPR1 mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.73
Clinical Summary— VIPR1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 84 VUS of 117 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.73LOEUF
pLI 0.000
Z-score -1.50
OE 1.31 (1.00–1.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.07Z-score
OE missense 0.99 (0.89–1.10)
259 obs / 262.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.31 (1.00–1.73)
0≤0.351.4
Missense OE0.99 (0.89–1.10)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 35 / 26.6Missense obs/exp: 259 / 262.0Syn Z: 0.97
DN
0.78top 25%
GOF
0.80top 10%
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

117 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS84
Likely Benign10
Benign8
6
Pathogenic
1
Likely Pathogenic
84
VUS
10
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
79
5
0
84
Likely Benign
0
6
2
2
10
Benign
0
4
0
4
8
Total089146109

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

View in ClinVar →

Protein Context — Lollipop Plot

VIPR1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
[VIPR1 promoter methylation promotes transcription factor AP-2alpha binding to inhibit VIPR1 expression and promote hepatocellular carcinoma cell growth in vitro].
Ning S et al.·Nan Fang Yi Ke Da Xue Xue Bao
2022
Identification of the Diagnostic Biomarker VIPR1 in Hepatocellular Carcinoma Based on Machine Learning Algorithm
Ge S et al.·J Oncol
2022
Overexpressing miR-122-5p Inhibits the Relaxation of Vaginal Smooth Muscle in Female Sexual Arousal Disorder by Targeting Vasoactive Intestinal Peptide Receptor 1
Cong S et al.·Sex Med
2021
lncRNA-AC079061.1/VIPR1 axis may suppress the development of hepatocellular carcinoma: a bioinformatics analysis and experimental validation
Lin XH et al.·J Transl Med
2022
Vasoactive Intestinal Peptide (VIP) Protects Nile Tilapia (Oreochromis niloticus) against Streptococcus agalatiae Infection
Zhang Z et al.·Int J Mol Sci
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients