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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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VIPR2
vasoactive intestinal peptide receptor 2
Chromosome 7 · 7q36.3
NCBI Gene: 7434Ensembl: ENSG00000106018.15HGNC: HGNC:12695UniProt: P41587
92PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
adenylate cyclase-activating G protein-coupled receptor signaling pathwayplasma membranepituitary adenylate cyclase-activating polypeptide receptor activityvasoactive intestinal polypeptide receptor activitymyopiarefractive errorProgressive visual lossCOVID-19
✦AI Summary

VIPR2 (vasoactive intestinal peptide receptor 2) is a G protein-coupled receptor located on chromosome 7.3 that binds vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) with binding affinity order PACAP38 = VIP > PACAP27 1. Ligand binding triggers conformational changes activating cAMP-dependent signaling pathways and potentially phospholipase C 1. VIPR2 functions as a homodimer through transmembrane domains 3-4, which is essential for efficient VIP binding and Gαi protein interaction 2. An intramolecular disulfide bond between Cys25 and Cys192 is functionally significant for downstream AKT phosphorylation 3. Clinically, VIPR2 dysfunction associates with multiple disorders. Microduplications at 7q36.3 containing VIPR2 are linked to schizophrenia and possibly autism spectrum disorder, potentially through disrupted cortical circuit maturation during development 14. Loss of VIPR2 function causes myopia in humans and mice by impairing bipolar cell signaling 5. VIPR2 regulates circadian rhythms and metabolic homeostasis; the rs6950857 variant association with metabolic syndrome is modifiable by seaweed consumption 6. Additionally, VIPR2 is expressed on innate lymphoid cells and may regulate immune responses 7. VIPR2 represents a therapeutic target for cancer progression, neuropsychiatric disorders, refractive errors, and metabolic disease.

Sources cited
1
VIPR2 binds VIP and PACAP with specific binding affinities; role in circadian rhythms, fear cognition, and cortical circuit maturation; VIPR2 microduplications linked to schizophrenia and autism spectrum disorder
PMID: 34366784
2
VIPR2 gene structure and low-copy repeats mediating rearrangements; rare microduplications involving VIPR2 associated with schizophrenia
PMID: 23073313
3
VIPR2 SNP rs6979985 associated with high myopia; VIPR2 knockout causes myopia through altered bipolar cell function and cAMP signaling
PMID: 33318135
4
VIPR2 structure and ligand-binding mechanism; disulfide bond between Cys25 and Cys192 functionally significant for VIPR2 signaling
PMID: 36332470
5
VIPR2 dimerization through transmembrane domains 3-4 essential for VIP binding and Gαi interaction; relevant to breast cancer progression
PMID: 40203889
6
VIPR2 rs6950857 variant involved in metabolic syndrome incidence; seaweed consumption modulates this association
PMID: 37807848
7
VIPR2 expressed on innate lymphoid cells with potential role in immune responses
PMID: 32017245
Disease Associationsⓘ20
myopiaOpen Targets
0.51Moderate
refractive errorOpen Targets
0.46Moderate
Progressive visual lossOpen Targets
0.46Moderate
COVID-19Open Targets
0.35Weak
Abnormality of refractionOpen Targets
0.34Weak
hidradenitisOpen Targets
0.34Weak
pathological myopiaOpen Targets
0.30Weak
ocular hypotensionOpen Targets
0.27Weak
atrial heart septal defectOpen Targets
0.19Weak
HypercholesterolemiaOpen Targets
0.19Weak
scoliosisOpen Targets
0.19Weak
myoepithelial tumorOpen Targets
0.11Weak
jaw diseaseOpen Targets
0.07Suggestive
cancerOpen Targets
0.05Suggestive
schizophreniaOpen Targets
0.04Suggestive
infectionOpen Targets
0.04Suggestive
hyper-IgE recurrent infection syndrome 5, autosomal recessiveOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
immunodeficiency 89 and autoimmunityOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PER2Protein interaction100%RAMP1Protein interaction96%NPPAProtein interaction91%FSHBProtein interaction91%TSHBProtein interaction91%GNB1Protein interaction90%
Tissue Expression6 tissues
Heart
100%
Ovary
85%
Brain
7%
Bone Marrow
5%
Lung
3%
Liver
2%
Gene Interaction Network
Click a node to explore
VIPR2PER2RAMP1NPPAFSHBTSHBGNB1
PROTEIN STRUCTURE
Preparing viewer…
PDB2X57 · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.81 [0.64–1.04]
RankingsWhere VIPR2 stands among ~20K protein-coding genes
  • #5,223of 20,598
    Most Researched92
  • #10,428of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedVIPR2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Probing the
PMID: 34366784
Front Neurosci · 2021
1.00
2
Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements.
PMID: 23073313
Eur J Hum Genet · 2013
0.90
3
Dysfunction of VIPR2 leads to myopia in humans and mice.
PMID: 33318135
J Med Genet · 2022
0.80
4
AlphaFold version 2.0 elucidates the binding mechanism between VIPR2 and KS-133, and reveals an S-S bond (Cys
PMID: 36332470
Biochem Biophys Res Commun · 2022
0.70
5
Structure of the human VIPR2 gene for vasoactive intestinal peptide receptor type 2.
PMID: 10481065
FEBS Lett · 1999
0.60