VIPR1

Summary

VIPR1 (vasoactive intestinal peptide receptor 1, HGNC:12694) is a protein-coding gene on chromosome 3p22.1, encoding Vasoactive intestinal polypeptide receptor 1 (P32241). G protein-coupled receptor activated by the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP).

This gene encodes a receptor for vasoactive intestinal peptide, a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7433 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 99 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004624

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12694
Approved symbol	VIPR1
Name	vasoactive intestinal peptide receptor 1
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	VPAC1, RDC1, HVR1, VPAC1R
Ensembl gene	ENSG00000114812
Ensembl biotype	protein_coding
OMIM	192321
Entrez	7433

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000325123, ENST00000433647, ENST00000436487, ENST00000439731, ENST00000439910, ENST00000443646, ENST00000446673, ENST00000450274, ENST00000465338, ENST00000473495, ENST00000473575, ENST00000487545, ENST00000490161, ENST00000495189, ENST00000498102, ENST00000883016, ENST00000883017, ENST00000883018, ENST00000883019, ENST00000883020, ENST00000883021, ENST00000883022, ENST00000883023, ENST00000883024, ENST00000883025, ENST00000883026, ENST00000883027, ENST00000883028, ENST00000883029, ENST00000883030, ENST00000913982, ENST00000954072, ENST00000954073

RefSeq mRNA: 5 — MANE Select: NM_004624 NM_001251882, NM_001251883, NM_001251884, NM_001251885, NM_004624

CCDS: CCDS2698, CCDS58828

Canonical transcript exons

ENST00000325123 — 13 exons

Exon	Start	End
ENSE00003460096	42519223	42519330
ENSE00003464487	42535343	42535384
ENSE00003488172	42530779	42530932
ENSE00003505964	42531471	42531531
ENSE00003516247	42527991	42528123
ENSE00003521687	42531803	42531869
ENSE00003527672	42534975	42535104
ENSE00003586884	42513749	42513854
ENSE00003601410	42532242	42532333
ENSE00003663519	42525887	42525993
ENSE00003790864	42527393	42527496
ENSE00003842902	42536090	42537568
ENSE00003843166	42502643	42502813

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.61.

FANTOM5 (CAGE): breadth broad, TPM avg 8.0133 / max 353.2848, expressed in 861 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36257	8.0133	861

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.61	gold quality
upper lobe of left lung	UBERON:0008952	97.34	gold quality
upper lobe of lung	UBERON:0008948	97.04	gold quality
mucosa of transverse colon	UBERON:0004991	95.38	gold quality
rectum	UBERON:0001052	94.19	gold quality
ileal mucosa	UBERON:0000331	93.76	gold quality
skin of leg	UBERON:0001511	93.25	gold quality
skin of abdomen	UBERON:0001416	92.60	gold quality
duodenum	UBERON:0002114	92.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.15	gold quality
lung	UBERON:0002048	91.53	gold quality
minor salivary gland	UBERON:0001830	91.44	gold quality
cerebellar hemisphere	UBERON:0002245	91.21	gold quality
cerebellar cortex	UBERON:0002129	91.07	gold quality
lower lobe of lung	UBERON:0008949	91.05	silver quality
zone of skin	UBERON:0000014	90.78	gold quality
transverse colon	UBERON:0001157	90.58	gold quality
granulocyte	CL:0000094	89.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.43	gold quality
right frontal lobe	UBERON:0002810	89.42	gold quality
jejunal mucosa	UBERON:0000399	89.30	gold quality
cerebellum	UBERON:0002037	88.99	gold quality
right lobe of liver	UBERON:0001114	88.95	gold quality
small intestine	UBERON:0002108	88.81	gold quality
saliva-secreting gland	UBERON:0001044	88.53	gold quality
colonic mucosa	UBERON:0000317	88.24	gold quality
mouth mucosa	UBERON:0003729	88.23	gold quality
prostate gland	UBERON:0002367	87.35	gold quality
monocyte	CL:0000576	86.94	gold quality
leukocyte	CL:0000738	86.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	14.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, IKZF1, NEUROD4, NR1H4

miRNA regulators (miRDB)

64 targeting VIPR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-508-5P	99.41	64.25	1248

Literature-anchored findings (GeneRIF, showing 40)

• Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros. (PMID:11812772)
• VPAC1 is a cellular neuroendocrine receptor expressed on T cells that actively facilitates productive HIV-1 infection. (PMID:11834941)
• Thus, the highly diverged chemical properties of the hydrophobic “YL” motif and charged “DR(Y)” motif could be a crucial difference between the Secretin Receptor Family and the Rhodopsin Family with respect to receptor activation and G-protein coupling. (PMID:11859928)
• VPAC1 receptor mRNA is expressed in the trigeminal, otic and superior cervical ganglia (prejunctional) and cerebral arteries (postjunctional). (PMID:11930171)
• a small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for the efficient agonist-stimulated intracellular calcium concentration increase (PMID:11981043)
• Genetic complexity of HVR1 quasispecies of hepatitis C virus in patients with cirrhosis. (PMID:12094871)
• a selective filter; Identification of a critical domain for restricting secretin binding (PMID:12133828)
• Vasoactive intestinal peptide (VIP) inhibits the proliferation of bone marrow progenitors through the VPAC1 receptor. (PMID:12225791)
• the role of charged residues in the intracellular loop 3 and the proximal C-terminal tail of hVPAC1 receptor for agonist-induced adenylyl cyclase activation (PMID:12690118)
• cloning and sequencing of 5’ flanking region; VPAC1 may play a functional role in development of both cerebellum and adrenal medulla (PMID:14599709)
• Data suggest that vasoactive intestinal peptide directly stimulates cortisol secretion from H295 cells via activation of the VPAC1 receptor subtype. (PMID:15171718)
• the hVPAC1 receptor binds to vasoactive intestinal peptide at its N-terminal ectodomain (PMID:15247290)
• Interaction of different G proteins with the recombinant VPAC1 receptor involves different receptor sub-domains. (PMID:15451021)
• the VPAC1 receptor carboxyl terminus has a role in agonist-induced receptor phosphorylation, internalization, and recycling (PMID:15932876)
• Farnesoid X receptor agonists may increase gallbladder fluid secretion through transcriptional activation of VPAC1. (PMID:16037943)
• analysis of the two-step activation mechanism of VPAC receptor and of class II G protein-coupled receptors (PMID:16520374)
• Thr429 phosphorylation has a role in activation of human VPAC1 (PMID:16554109)
• 125I-[Bpa28-vasoactive intestinal peptide] was covalently bonded to the 121-133 fragment within the N-terminal ectodomain of the receptor (PMID:16888162)
• Photoaffinity experiments clearly indicated that the 6-28 part of VIP physically interacts with the N-terminal ectodomain of VPAC1 receptor (PMID:16888167)
• MCF-7 cells have VPAC1 receptors that bound the VIP chemotherapeutic conjugate (PMID:16888206)
• observations provide additional evidence for a role of proapoptotic caspase adaptor protein and PAC1 R in the events determining the outcome of prostate cancer (PMID:16888207)
• identification and characterization of novel five-transmembrane(5TM) isoforms of VPAC1 (PMID:16934434)
• expression of VIP receptor-1 (VPAC1) and VPAC2 in CD4+ T cells changed reciprocally in the context of the activation state (PMID:17077178)
• The differential expression of VIPR1 in ulcerative colitis and Crohn’s disease mucosa suggests that the VIP system plays different roles in the pathogenesis of inflammatory bowel disease. (PMID:17611633)
• Both intra- and extracellular Ca2+ play a role in controlling pro-inflammatory functions stimulated by PACAP which acts through a VPAC-1, FPRL1/Galphai/PI3K/ERK pathway and a VPAC-1/Galphas/PKA/p38 pathway to fully activate monocytes (PMID:17651798)
• analysis of VIP 16gamma-glutamyl diamino derivative positive charges on hVPAC1 and hVPAC2 receptor function (PMID:17883247)
• Structural studies provide a detailed molecular understanding of the VIP-VPAC1 receptor interaction. (PMID:17885205)
• VPAC1 signaling tempers normal megakaryopoiesis, and inhibition of this pathway stimulates megakaryocyte differentiation. (PMID:18000164)
• Proinflammatory effect of VIP is mediated via the specific G protein-coupled receptor VIP/pituitary adenylate cyclase-activating protein (VPAC1) receptor as well as via FPRL1. (PMID:18174366)
• VIP and PACAP levels were decreased in anterior vaginal wall of stress urinary incontinence and pelvic organ prolapse patients,they may participate in the pathophysiology of these diseases. (PMID:18351280)
• deficient expression of VPAC1 (vasoactive intestinal peptide receptor 1) in immune cells of Rheumatoid Arthritis was associated with the predominant proinflammatory Th1 mileu; reduced VPAC1 expression in RA is associated with genetic polymorphism (PMID:18383379)
• Results indicate that the N-terminal part of VIP physically interacts with the N-ted in the continuity of 6-28 VIP sequence; and the N-terminal part of VIP and its antagonist (PG97-269) have different sites of interaction with the VPAC1 receptor N-ted. (PMID:18597186)
• VIP acts in an autocrine fashion via VPAC1 to inhibit megakaryocyte proliferation and induce proplatelet formation (PMID:18663606)
• HLA-B (*)2705 and a functional polymorphism in VIPR1 gene, might be due to a founder effect or might be the result of a selective pressure. Consequent downregulation of this receptor in presence of a ‘danger’ signal might influence susceptibility to AS. (PMID:18668120)
• Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype of VIPR1 distribution of snps (PMID:19309439)
• We describe significant upregulation of the SPP1 gene, downregulation of VIPR1, and losses of the VIPR1 gene. (PMID:20014941)
• Results indicate that VPAC1, but not VPAC2 or PAC1, up-regulation in macrophages is a common mechanism in response to acute and chronic pro-inflammatory stimuli. (PMID:20026142)
• Moreover, we report the markedly nuclear localization of VPAC(1) receptors in estrogen-dependent (T47D) and independent (MDA-MB-468) human breast cancer cell lines (PMID:20691743)
• role of in MicroRNA 525-5p down-modulating VPAC1 expressio (PMID:20706588)
• The VIPR1 polymorphism, previously linked to gastrointestinal dysmotility disorders, does not represent a common risk factor for gallstones in the general or in an elderly population. (PMID:20922191)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vipr1b	ENSDARG00000059058
mus_musculus	Vipr1	ENSMUSG00000032528
rattus_norvegicus	Vipr1	ENSRNOG00000047457

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Vasoactive intestinal polypeptide receptor 1 — P32241 (reviewed: P32241)

Alternative names: Pituitary adenylate cyclase-activating polypeptide type II receptor, VPAC1 receptor

All UniProt accessions (4): P32241, C9JDT8, C9JH33, F2Z2U6

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor activated by the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP). Binds VIP and both PACAP27 and PACAP38 bioactive peptides with the following order of ligand affinity VIP = PACAP27 > PACAP38. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Activates cAMP-dependent pathway.

Subunit / interactions. Interacts with ADCYAP1/PACAP; activated by both PACAP27 and PACAP38 neuropeptides. Interacts with VIP; the interaction results in VIPR1 activation.

Subcellular location. Cell membrane.

Tissue specificity. In lung, HT-29 colonic epithelial cells, Raji B-lymphoblasts. Lesser extent in brain, heart, kidney, liver and placenta. Not expressed in CD4+ or CD8+ T-cells. Expressed in the T-cell lines HARRIS, HuT 78, Jurkat and SUP-T1, but not in the T-cell lines Peer, MOLT-4, HSB and YT.

Similarity. Belongs to the G-protein coupled receptor 2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P32241-1	Short, hIVR8	yes
P32241-2	Long, hIVR5
P32241-3	3
P32241-4	4
P32241-5	5

RefSeq proteins (5): NP_001238811, NP_001238812, NP_001238813, NP_001238814, NP_004615* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000832	GPCR_2_secretin-like	Family
IPR001571	GPCR_2_VIP_rcpt	Family
IPR001771	GPCR_2_VIP_rcpt_1	Family
IPR001879	GPCR_2_extracellular_dom	Domain
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR050332	GPCR_2	Family

Pfam: PF00002, PF02793

UniProt features (67 total): helix 18, topological domain 8, strand 8, transmembrane region 7, disulfide bond 5, splice variant 5, glycosylation site 4, sequence conflict 4, turn 3, sequence variant 2, signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
5IB2	X-RAY DIFFRACTION	1.44
1OGT	X-RAY DIFFRACTION	1.47
5DEF	X-RAY DIFFRACTION	1.6
3B6S	X-RAY DIFFRACTION	1.8
7ALO	X-RAY DIFFRACTION	1.8
5DEG	X-RAY DIFFRACTION	1.83
3B3I	X-RAY DIFFRACTION	1.86
5IB1	X-RAY DIFFRACTION	1.91
5IB3	X-RAY DIFFRACTION	1.91
3HCV	X-RAY DIFFRACTION	1.95
5IB4	X-RAY DIFFRACTION	1.95
3DTX	X-RAY DIFFRACTION	2.1
1OF2	X-RAY DIFFRACTION	2.2
8E3Y	ELECTRON MICROSCOPY	2.3
5IB5	X-RAY DIFFRACTION	2.49
8E3Z	ELECTRON MICROSCOPY	2.7
6VN7	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32241-F1	76.72	0.30

Antibody-complex structures (SAbDab): 3 — 6VN7, 8E3Y, 8E3Z

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 37–208, 50–72, 63–105, 86–122, 215–285

Glycosylation sites (4): 58, 69, 100, 290

Mutagenesis-validated functional residues (1):

Position	Phenotype
139	decreased adcyap1/pacap27 potency for vipr1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-420092	Glucagon-type ligand receptors

MSigDB gene sets: 214 (showing top): MODULE_92, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, MODULE_274, MODULE_64, MODULE_329, PID_REG_GR_PATHWAY, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MODULE_75, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, MODULE_206, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, CAIRO_HEPATOBLASTOMA_DN, chr3p22, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_DN

GO Biological Process (7): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cell population proliferation (GO:0008284), signal transduction (GO:0007165)

GO Molecular Function (7): pituitary adenylate cyclase-activating polypeptide receptor activity (GO:0001634), vasoactive intestinal polypeptide receptor activity (GO:0004999), G protein-coupled peptide receptor activity (GO:0008528), peptide hormone binding (GO:0017046), transmembrane signaling receptor activity (GO:0004888), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	4
G protein-coupled receptor signaling pathway	3
signal transduction	2
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
peptide receptor activity	1
hormone binding	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VIPR1	VIP	P01282	999
VIPR1	ADCYAP1	P18509	999
VIPR1	ATG5	Q9H1Y0	988
VIPR1	RAMP2	O60895	941
VIPR1	WASL	O00401	876
VIPR1	SCT	P09683	772
VIPR1	RAMP1	O60894	766
VIPR1	RAMP3	O60896	743
VIPR1	VIPR2	P41587	710
VIPR1	HTR1D	P28221	681
VIPR1	ADORA1	P30542	678
VIPR1	PPIP5K1	Q6PFW1	665
VIPR1	ERVFRD-1	P60508	642
VIPR1	ERV3-1	Q14264	642
VIPR1	GCG	P01275	632

IntAct

13 interactions, top by confidence:

A	B	Type	Score
VIPR1	PRDM5	psi-mi:“MI:0915”(physical association)	0.560
VIPR1	HLA-A	psi-mi:“MI:0407”(direct interaction)	0.440
VIPR1	VIP	psi-mi:“MI:0915”(physical association)	0.400
VIP	VIPR1	psi-mi:“MI:0915”(physical association)	0.400
VIPR1	CALM1	psi-mi:“MI:0915”(physical association)	0.400
TINF2	VIPR1	psi-mi:“MI:0915”(physical association)	0.370
VIPR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
VIPR1	SLC33A1	psi-mi:“MI:0914”(association)	0.350
VIPR1	ATP9A	psi-mi:“MI:0914”(association)	0.350
VIPR1	PRDM5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (209): REEP6 (Affinity Capture-MS), SC5D (Affinity Capture-MS), KIAA1244 (Affinity Capture-MS), XPO6 (Affinity Capture-MS), MFSD5 (Affinity Capture-MS), RNF13 (Affinity Capture-MS), DYM (Affinity Capture-MS), YIPF3 (Affinity Capture-MS), GPR89A (Affinity Capture-MS), PTPLB (Affinity Capture-MS), SLC7A2 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP8 (Affinity Capture-MS), AGPAT4 (Affinity Capture-MS), EBP (Affinity Capture-MS)

ESM2 similar proteins: A0A2Z2U4G9, O35659, O46502, O95838, P23811, P25107, P25117, P25961, P30082, P30083, P30988, P32082, P32214, P32215, P32241, P32301, P34999, P35000, P41587, P41588, P41593, P43218, P43219, P43220, P47871, P47872, P48546, P49190, P50133, P51839, P70555, P79222, P97751, Q02643, Q02644, Q03431, Q0P543, Q1LZF7, Q28992, Q29627

Diamond homologs: A0A2Z2U4G9, A6QP74, O35659, O42602, O42603, O46502, O62772, O95838, P23811, P25107, P25117, P25961, P30082, P30083, P32082, P32215, P32241, P32301, P34998, P34999, P35000, P35347, P35353, P41586, P41587, P41588, P41593, P43218, P43219, P43220, P47866, P47871, P47872, P48546, P48960, P49190, P50133, P70205, P70555, P97751

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ADCYAP1	up-regulates	VIPR1	binding
VIP	up-regulates	VIPR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

99 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	10
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2193 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42513745:TCAG:T	acceptor_loss	1.0000
3:42513746:CAG:C	acceptor_loss	1.0000
3:42513747:A:AG	acceptor_gain	1.0000
3:42513747:A:G	acceptor_loss	1.0000
3:42513748:G:GG	acceptor_gain	1.0000
3:42519221:A:AC	acceptor_loss	1.0000
3:42519221:A:AG	acceptor_gain	1.0000
3:42519222:G:GC	acceptor_loss	1.0000
3:42519222:G:GG	acceptor_gain	1.0000
3:42519327:CAAG:C	donor_loss	1.0000
3:42519328:AAG:A	donor_loss	1.0000
3:42519331:GTAA:G	donor_loss	1.0000
3:42519332:T:A	donor_loss	1.0000
3:42527388:A:AG	acceptor_gain	1.0000
3:42527391:A:AG	acceptor_gain	1.0000
3:42527392:G:GC	acceptor_gain	1.0000
3:42527392:GC:G	acceptor_gain	1.0000
3:42527392:GCA:G	acceptor_gain	1.0000
3:42527392:GCAGC:G	acceptor_gain	1.0000
3:42527493:TCAG:T	donor_loss	1.0000
3:42527496:GGT:G	donor_loss	1.0000
3:42527497:G:A	donor_loss	1.0000
3:42527498:T:G	donor_loss	1.0000
3:42530776:CA:C	acceptor_loss	1.0000
3:42530777:AGGT:A	acceptor_gain	1.0000
3:42530777:AGGTG:A	acceptor_gain	1.0000
3:42530778:G:GT	acceptor_loss	1.0000
3:42530778:GGT:G	acceptor_gain	1.0000
3:42530778:GGTG:G	acceptor_gain	1.0000
3:42530778:GGTGG:G	acceptor_gain	1.0000

AlphaMissense

2997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42519257:G:C	W73C	0.998
3:42519257:G:T	W73C	0.998
3:42525924:G:C	W110C	0.998
3:42525924:G:T	W110C	0.998
3:42519239:G:C	W67C	0.996
3:42519239:G:T	W67C	0.996
3:42530929:T:A	W263R	0.995
3:42530929:T:C	W263R	0.995
3:42531809:G:C	W286C	0.995
3:42531809:G:T	W286C	0.995
3:42530836:T:A	W232R	0.994
3:42530836:T:C	W232R	0.994
3:42525922:T:A	W110R	0.993
3:42525922:T:C	W110R	0.993
3:42525907:T:A	C105S	0.992
3:42525908:G:C	C105S	0.992
3:42535343:G:C	G381R	0.992
3:42519255:T:A	W73R	0.991
3:42519255:T:C	W73R	0.991
3:42525902:G:C	R103P	0.990
3:42527439:G:A	G149D	0.990
3:42528029:T:C	L181P	0.989
3:42535369:C:G	C389W	0.989
3:42519225:T:A	C63S	0.987
3:42519226:G:C	C63S	0.987
3:42528019:C:G	H178D	0.987
3:42535367:T:C	C389R	0.987
3:42530829:C:A	N229K	0.986
3:42530829:C:G	N229K	0.986
3:42530849:A:T	E236V	0.986

dbSNP variants (sampled 300 via entrez): RS1000156453 (3:42501054 G>A), RS1000178806 (3:42510245 G>A,C), RS1000354431 (3:42489904 C>G,T), RS1000402206 (3:42501390 T>C), RS1000423484 (3:42503997 T>C), RS1000455903 (3:42516292 G>A,C,T), RS1000544230 (3:42509298 A>G), RS1000567232 (3:42536077 T>C), RS1000746918 (3:42518255 G>C), RS1000831582 (3:42505755 G>A), RS1000847699 (3:42516597 T>A,G), RS1000852192 (3:42526949 G>A), RS1000884043 (3:42505993 G>A,T), RS1000943751 (3:42511879 G>A,C), RS1000947294 (3:42521039 G>T)

Disease associations

OMIM: gene MIM:192321 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003134_7	Cerebrospinal fluid clusterin levels	3.000000e-06
GCST008103_63	Bipolar disorder	6.000000e-07
GCST008156_140	Hip circumference adjusted for BMI	8.000000e-06
GCST012299_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524128 (PROTEIN FAMILY), CHEMBL5144 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 207 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1933349	MK-0893	2	207

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — VIP and PACAP receptors

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
[Ala11,22,28]VIP	Agonist	10.2	pEC50
VIP	Agonist	10.0	pEC50
[125I]VIP (human, mouse, rat)	Agonist	9.4	pKd
N-stearyl-[Nle17]VIP	Agonist	8.3	pIC50
[Lys15,Arg16,Leu27]VIP-(1-7)/GRF-(8-27)-NH2	Agonist	7.7	pIC50
PACAP-27	Agonist	7.6	pEC50
N-stearyl-[Nle17] neurotensin-(6-11)/VIP-(7-28)	Antagonist	7.5	pIC50
PACAP-38	Agonist	7.4	pEC50
[Arg16]chicken secretin	Agonist	7.2	pIC50
PG 97-269	Antagonist	7.1	pIC50
GHRH	Agonist	6.2	pKi
Ro 25-1553	Partial agonist	6.0	pEC50
PHI	Agonist	6.0	pIC50
helodermin	Agonist	6.0	pIC50
PHM	Agonist	5.7	pKi
PG 99-465	Agonist	5.5	pEC50
PHV	Agonist	5.5	pIC50
Ro 25-1392	Agonist	5.5	pKi
BAY 55-9837	Agonist	5.1	pIC50
secretin	Agonist	5.0	pKi

Binding affinities (BindingDB)

2 measured of 3 human assays (5 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NSC_0	KI	1.7 nM
Ac-L-His-L-Ser-L-Asp-L-Ala-L-Val-L-Phe-L-Thr-L-Glu-L-Asn-L-Tyr-L-Thr-L-Lys-L-Leu-L-Arg-L-Lys-L-Gln-L-Nle-L-Ala-L-Ala-L-Lys-L-Lys(1)-L-Tyr-L-Leu-L-Asn-L-Asp(1)-L-Leu-L-Lys-L-Lys-Gly-Gly-L-Thr-NH2	KI	1020 nM

ChEMBL bioactivities

44 potent at pChembl≥5 of 45 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	EC50	0.02	nM	CHEMBL1893324
10.52	EC50	0.03	nM	CHEMBL5220770
10.40	IC50	0.04	nM	CHEMBL524658
10.30	IC50	0.05	nM	CHEMBL524658
10.21	Ki	0.062	nM	CHEMBL1893324
10.17	Ki	0.067	nM	CHEMBL1893324
9.96	IC50	0.11	nM	CHEMBL1893324
9.96	IC50	0.11	nM	CHEMBL3884667
9.92	IC50	0.12	nM	CHEMBL1893324
9.71	EC50	0.1952	nM	CHEMBL4294827
9.57	IC50	0.27	nM	CHEMBL1893324
9.45	EC50	0.3575	nM	CHEMBL4280734
9.33	IC50	0.47	nM	CHEMBL4128926
9.22	EC50	0.6	nM	CHEMBL219499
8.66	EC50	2.17	nM	CHEMBL4295255
8.35	EC50	4.426	nM	CHEMBL4281814
8.31	IC50	4.9	nM	CHEMBL4296687
8.25	EC50	5.658	nM	CHEMBL4277709
8.23	IC50	5.888	nM	CHEMBL524852
8.05	IC50	9	nM	CHEMBL3736134
8.04	EC50	9.088	nM	CHEMBL4294843
8.03	IC50	9.333	nM	CHEMBL3736134
8.02	EC50	9.515	nM	CHEMBL4291119
7.99	EC50	10.24	nM	CHEMBL4295255
7.94	IC50	11.48	nM	CHEMBL3736230
7.92	IC50	12	nM	CHEMBL3736230
7.92	IC50	12	nM	CHEMBL219499
7.85	IC50	14.13	nM	CHEMBL507480
7.19	EC50	64.4	nM	CHEMBL4284839
7.15	EC50	71.18	nM	CHEMBL4281905
7.05	EC50	89.34	nM	CHEMBL4282941
6.93	IC50	118.4	nM	CHEMBL5219662
6.88	EC50	133	nM	CHEMBL4282016
6.66	EC50	217.7	nM	CHEMBL4277441
6.53	EC50	293	nM	CHEMBL4286419
6.34	EC50	461.4	nM	CHEMBL4290756
6.29	EC50	516.3	nM	CHEMBL4277799
6.11	EC50	785.3	nM	CHEMBL4291903
6.04	EC50	912.1	nM	CHEMBL4277783
6.03	EC50	931.8	nM	CHEMBL4284961
5.85	EC50	1420	nM	CHEMBL4282364
5.85	EC50	1420	nM	CHEMBL4277870
5.82	EC50	1530	nM	CHEMBL4287451

PubChem BioAssay actives

22 with measured affinity, of 141 total; 12 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1915941: Agonist activity at VPAC1 in human SH-SY5Y cells assessed as cAMP accumulation incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay	ec50	<0.0001	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1915941: Agonist activity at VPAC1 in human SH-SY5Y cells assessed as cAMP accumulation incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay	ec50	<0.0001	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1336346: Displacement of [125I]PACAP1-27 from human recombinant PAC1 receptor expressed in CHO cells measured after 120 mins by scintillation counting method	ic50	<0.0001	uM
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1336366: Displacement of [125I]VIP from human recombinant VPAC1 receptor expressed in CHO cells measured after 60 mins by scintillation counting method	ic50	0.0001	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494772: Displacement of [125I]VIP from human recombinant VPAC1 receptor after 60 mins by scintillation counting analysis	ic50	0.0005	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoic acid	274568: Activity at human VPAC1 receptor in CHO cells by measuring cAMP accumulation	ec50	0.0006	uM
(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid	340269: Inhibition of human VIP1 receptor	ic50	0.0049	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0059	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-[4-[2-(4-fluorophenyl)ethynyl]phenyl]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0090	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-[4-(2-phenylethynyl)phenyl]propan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0115	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0141	uM
(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-sulfanylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]hexanoic acid	1915944: Antagonist activity at VPAC1 in human SH-SY5Y cells assessed as inhibition of PACAP38-induced cAMP accumulation pre-incubated for 30 mins followed by agonist addition and measured after 75 mins by Eu-cAMP tracer based LANCE ultra cAMP assay	ic50	0.1184	uM

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	7
Particulate Matter	decreases reaction, increases expression, increases abundance	4
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
chloroacetaldehyde	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression, increases abundance	1
arsenite	increases methylation	1
afimoxifene	increases expression	1
sodium arsenite	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-nonylphenol	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-tert-octylphenol	affects cotreatment, decreases expression	1
GW 4064	decreases reaction, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
Nebivolol	increases expression	1
Zoledronic Acid	increases expression	1
Cidofovir	increases expression	1
Alitretinoin	decreases reaction, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	decreases reaction, increases expression	1
Chenodeoxycholic Acid	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1

ChEMBL screening assays

83 unique, capped per target: 71 binding, 12 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4880302	Binding	Vasoactive intestinal peptide receptor CEREP ligand profiling	Data for DCP probe ABT-546
CHEMBL2160607	Functional	Antagonist activity at human VPAC1 expressed in HT-29 cells assessed as inhibition of glucagon-induced cAMP accumulation preincubated for 30 mins prior to glucagon challenge measured after 30 mins post glucagon challenge by liquid scintilla	Discovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes. — J Med Chem

Cellosaurus cell lines

9 cell lines: 4 spontaneously immortalized cell line, 3 transformed cell line, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0TV	ACTOne VIPR1	Transformed cell line	Female
CVCL_H510	CHO-K1/VPAC1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV88	cAMP Hunter CHO-K1 VIPR1 Gs/Gq	Spontaneously immortalized cell line	Female
CVCL_KZ24	PathHunter CHO-K1 VIPR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB47	PathHunter U2OS VIPR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_T424	Psi-CRIP-RxhVIPR-bsr	Transformed cell line	Male
CVCL_YK24	HEK293 VIPR1 HiTSeeker	Transformed cell line	Female
CVCL_YK65	U2OS VIPR1 cAMP-Nomad	Cancer cell line	Female
CVCL_ZK84	GeneBLAzer VPAC1-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.