VIP

Summary

VIP (vasoactive intestinal peptide, HGNC:12693) is a protein-coding gene on chromosome 6q25.2, encoding VIP peptides (P01282). VIP is a neuropeptide involved in a diverse array of physiological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors: VIP receptor 1 (VPR1) and VIP receptor 2 (VPR2).

The protein encoded by this gene belongs to the glucagon family. It stimulates myocardial contractility, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.

Source: NCBI Gene 7432 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Asperger syndrome (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 14 total
• Druggable target: yes
• MANE Select transcript: NM_003381

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12693
Approved symbol	VIP
Name	vasoactive intestinal peptide
Location	6q25.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000146469
Ensembl biotype	protein_coding
OMIM	192320
Entrez	7432

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000367243, ENST00000367244, ENST00000431366, ENST00000897583, ENST00000897584, ENST00000897585, ENST00000897586, ENST00000897587

RefSeq mRNA: 2 — MANE Select: NM_003381 NM_003381, NM_194435

CCDS: CCDS5240, CCDS5241

Canonical transcript exons

ENST00000367244 — 7 exons

Exon	Start	End
ENSE00000976009	152754166	152754288
ENSE00000976010	152755269	152755373
ENSE00000976011	152756134	152756265
ENSE00000976012	152757096	152757184
ENSE00001443920	152752168	152752284
ENSE00003841961	152750797	152750959
ENSE00003848106	152758910	152759760

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 96.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1087 / max 347.7204, expressed in 113 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70653	1.1087	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	96.53	gold quality
rectum	UBERON:0001052	96.20	gold quality
caecum	UBERON:0001153	95.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.68	gold quality
mucosa of stomach	UBERON:0001199	88.97	gold quality
endothelial cell	CL:0000115	88.59	gold quality
transverse colon	UBERON:0001157	87.30	gold quality
cingulate cortex	UBERON:0003027	85.65	gold quality
anterior cingulate cortex	UBERON:0009835	85.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.32	gold quality
lower esophagus	UBERON:0013473	85.10	gold quality
sigmoid colon	UBERON:0001159	84.87	gold quality
prefrontal cortex	UBERON:0000451	84.59	gold quality
large intestine	UBERON:0000059	84.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.17	gold quality
colon	UBERON:0001155	84.12	gold quality
intestine	UBERON:0000160	83.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.17	gold quality
colonic epithelium	UBERON:0000397	83.04	gold quality
right frontal lobe	UBERON:0002810	82.34	gold quality
Brodmann (1909) area 10	UBERON:0013541	82.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.76	gold quality
amygdala	UBERON:0001876	81.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.89	gold quality
frontal cortex	UBERON:0001870	80.33	gold quality
neocortex	UBERON:0001950	80.31	gold quality
small intestine	UBERON:0002108	80.16	gold quality
mucosa of transverse colon	UBERON:0004991	79.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1882.14
E-HCAD-30	no	204.63
E-ANND-3	no	2.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPD, CEBPG, CREB1, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, JUND, NFKB, NR4A2, POU1F1, POU2F2, REST, SMAD3, SMAD4, SP1, SPI1, STAT1, STAT3

miRNA regulators (miRDB)

85 targeting VIP, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 40)

• Besides their presence and functions in the gut and the brain VIP and PACAP have distinct physiological roles in the genital tract. (PMID:11713978)
• Circulating VIP in fulminant hepatic failure seems to reflect hemodynamic changes in the systemic rather than in the cerebral circulation. (PMID:11884208)
• mRNA of this peptide and immunoreactivity are decreased in a fetal alcohol syndrome model. (PMID:12220738)
• Vasoactive intestinal peptide (VIP) inhibits the proliferation of bone marrow progenitors through the VPAC1 receptor. (PMID:12225791)
• VIP modulation of neural crest differentiation is mediated via VPAC1 and high expression of VPAC1 induces differentiation in and decreases tumorigenicity of neuroblastoma cells. (PMID:12409228)
• Atopic dermatitis patients’ VIP levels were elevated not only in the skin but also in the serum, suggesting that increased serum levels in might be involved in its pathogenesis. (PMID:12670727)
• VIP has a role in downregulating interferon gamma in the inflammatory response in the central nervous system (PMID:12754213)
• We report here a repressor element, similar to the canonical restrictive element-1 (RE-1), located within the first non-coding exon of the human VIP gene. Endogenous RE-1 silencer factor regulates VIP gene expression in neuroblastic and non-neuronal cells (PMID:15009665)
• VIP induces neuroendocrine differentiation in prostate cancer cells and has proangiogenic potential (PMID:15093699)
• Thus, in human skin, VIP-mediated vasodilation includes a NO-dependent component that could not be explained by H1- and H2-receptor activation. (PMID:15155712)
• the central part of VIP, at least between Phe(6) and Tyr(22), interacts with the N-terminal ectodomain of the hVPAC1 receptor (PMID:15247290)
• Results show that the combination of different amino terminal and intracellular loop 3 splicing variants in the PAC1 receptor dictates the ability of agonists, including PACAP and VIP, to activate signaling pathways. (PMID:16226889)
• VIP and PACAP stimulate the synthesis and release of adrenomedullary catecholamines, and all three subtypes of PACAP/VIP Rs mediate this effect, PAC(1)-Rs being coupled to AC, VPAC(1)-Rs to both AC and PLC, and VPAC(2)-Rs only to PLC. (PMID:16697281)
• antiapoptotic signaling pathways activated by vasoactive intestinal polypeptide, epidermal growth factor, and phosphatidylinositol 3-kinase in prostate cancer cells converge on BAD (PMID:16728406)
• HNF4alpha, CREM, HNF1alpha, and C/EBPalpha have roles in transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine (PMID:16893891)
• Has protective effects against human bronchial epithelial cell damage. (PMID:16965837)
• Study investigated the relevance of genetic alterations in VIP to the development of idiopathic pulmonary arterial hypertension; analysis of VIP gene from 10 patients could not be correlated with the disease. (PMID:17003842)
• SP, CGRP and VIP may play important roles in the pathophysiological mechanism of vasomotor rhinitis. (PMID:17087112)
• VIP has an inhibitory effect on IL-1beta-induced ICAM-1 expression in serous fibroblasts, which may be associated with NF-kappaB activity (PMID:17275031)
• This paper reviews the role of VIP in neurodevelopment, its known involvement in neurodevelopmental disorders and proposes ways in which VIP might be of therapeutic value. (PMID:17430171)
• The aim of this review is (1) to update our knowledge of the cellular and molecular events relevant to VIP function in the immune system; and (2) to gather recent data that support its role as a type 2 cytokine. (PMID:17430175)
• inflammation is associated with a differential expression of VIP and nNOS neuronal subpopulations within the two major enteric plexi, likely due to phenotypic switch in Crohn disease (PMID:17466601)
• a proangiogenic potential of vasoactive intestinal peptide in breast cancer. (PMID:17683807)
• in trophic and anti-inflammatory VIP effects occurs in areas exhibiting a very marked inflammation (PMID:17804556)
• Structural studies provide a detailed molecular understanding of the VIP-VPAC1 receptor interaction. (PMID:17885205)
• The abnormal excretion of hormonal factors is closely related to gallstone formation (PMID:18234640)
• 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)
• VIP(Vasoactive intestinal peptide) expression was decreased in Rhematoid Arthritis (RA) synovial fibroblasts (FLS) compared with Osteoarthritis(OA) FLS;in RA FLS, VPAC2 (VIP receptor type 2) mediates the antiinflammatory effects of VIP (PMID:18383383)
• study demonstrated the role of corneal endothelial cell VIP in maintaining the expression level of a corneal endothelial differentiation marker, N-cadherin, and the hexagonal cell shape (PMID:18441300)
• The antimicrobial peptide, VIP is a neuropeptide with activity against a range of microorganisms from skin, oral, respiratory and gastrointestinal tract sites. (PMID:18603306)
• VIP acts in an autocrine fashion via VPAC1 to inhibit megakaryocyte proliferation and induce proplatelet formation (PMID:18663606)
• These results suggest that the VIP-mediated wound repair of HBECs is associated with activation of CREB via PKA and ERK dependent pathway. (PMID:19136032)
• VIP secreting Neuroblastic tumors are usually associated with differentiation; they can also secondarily arise from a high-risk tumor upon treatment (PMID:19143025)
• secretin stimulates VIP release from postganglionic neurons in the gastric myenteric plexus. (PMID:19239625)
• There is evidence that VIP is a neurotransmitter in the vaginal epithelium. The anterior vaginal wall has a more important role than the posterior wall. Change of VIP is related to age in pelvic organ prolapse patients. (PMID:19272598)
• Reduction in the quantitative sudomotor axon reflex test and VIP expression in the sweat glands might be involved in the dyshidrosis of PD patients. (PMID:19476518)
• Investigated the correlation between VIP gene variants and idiopathic pulmonary arterial hypertension (IPAH) in Chinese population. The VIP gene variant g.8129T–>C may be one of the risk factors in the pathogenesis of IPAH. (PMID:19508420)
• The VIP level of the nasal septum in the perennial allergic rhinitis patients was higher than that in the normal controls. (PMID:19685709)
• Results suggest for the first time a role of FOS in PACAP-induced VIP gene expression in human NB-1 neuroblastoma cells. (PMID:19712974)
• Relaxation reaction via VIP nerves and contraction via SP nerves might be involved in regulation of enteric nervous system in the normal human PS. (PMID:19950799)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vip	ENSDARG00000078247
danio_rerio	vipb	ENSDARG00000079443
mus_musculus	Vip	ENSMUSG00000019772
rattus_norvegicus	Vip	ENSRNOG00000018808

Paralogs (2): GHRH (ENSG00000118702), ADCYAP1 (ENSG00000141433)

Protein

Protein identifiers

VIP peptides — P01282 (reviewed: P01282)

All UniProt accessions (2): P01282, H0Y763

UniProt curated annotations — full annotation on UniProt →

Function. VIP is a neuropeptide involved in a diverse array of physiological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors: VIP receptor 1 (VPR1) and VIP receptor 2 (VPR2). Abundantly expressed throughout the CNS and peripheral nervous systems where they primarily exert neuroprotective and immune modulatory roles. Also causes vasodilation, lowers arterial blood pressure, stimulates myocardial contractility, increases glycogenolysis and relaxes the smooth muscle of trachea, stomach and gall bladder. Bioactive forms that cause vasodilation. PHM-27 is a potent agonist of the calcitonin receptor CALCR, with similar efficacy as calcitonin. Bioactive forms that cause vasodilation.

Subcellular location. Secreted.

Similarity. Belongs to the glucagon family.

Isoforms (2)

UniProt ID	Names	Canonical?
P01282-1	1	yes
P01282-2	2

RefSeq proteins (2): NP_003372, NP_919416 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000532	Glucagon_GIP_secretin_VIP	Domain
IPR046963	VIP/GHRH-like	Family

Pfam: PF00123

UniProt features (14 total): sequence conflict 3, peptide 3, modified residue 3, propeptide 2, signal peptide 1, helix 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8E3Z	ELECTRON MICROSCOPY	2.7
9P93	ELECTRON MICROSCOPY	3.2
9P92	ELECTRON MICROSCOPY	3.8
2RRH	SOLUTION NMR
2RRI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01282-F1	67.73	0.16

Antibody-complex structures (SAbDab): 3 — 8E3Z, 9P92, 9P93

Functional residue map

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

Post-translational modifications (3): 76, 107, 152

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: 195 (showing top): ATF_B, MODULE_92, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, NKX25_02, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, STAT3_01, AAAYRNCTG_UNKNOWN, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (10): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), body fluid secretion (GO:0007589), positive regulation of cell population proliferation (GO:0008284), regulation of protein localization (GO:0032880), positive regulation of protein catabolic process (GO:0045732), epinephrine secretion (GO:0048242), mRNA stabilization (GO:0048255), prolactin secretion (GO:0070459), positive regulation of cAMP/PKA signal transduction (GO:0141163)

GO Molecular Function (6): hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), type 1 vasoactive intestinal polypeptide receptor binding (GO:0031891), type 2 vasoactive intestinal polypeptide receptor binding (GO:0031892), peptide hormone receptor binding (GO:0051428), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), neuron projection (GO:0043005)

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
vasoactive intestinal polypeptide receptor binding	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
secretion	1
regulation of body fluid levels	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
intracellular protein localization	1
regulation of localization	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
catecholamine secretion	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
protein secretion	1
peptide hormone secretion	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
positive regulation of intracellular signal transduction	1
receptor ligand activity	1
hormone activity	1
neuropeptide activity	1
hormone receptor binding	1
binding	1
cellular anatomical structure	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VIP	VIPR2	P41587	999
VIP	VIPR1	P32241	999
VIP	SCT	P09683	987
VIP	NPY	P01303	973
VIP	TAC1	P20366	970
VIP	ADCYAP1R1	P41586	966
VIP	SCTR	P47872	935
VIP	SST	P01166	932
VIP	GHRH	P01286	930
VIP	GAL	P22466	923
VIP	GRP	P07491	919
VIP	GLP1R	P43220	882
VIP	CRH	P06850	861
VIP	GIP	P09681	861
VIP	CCK	P06307	856

IntAct

13 interactions, top by confidence:

A	B	Type	Score
VIP	SGTA	psi-mi:“MI:0915”(physical association)	0.560
FAP	VIP	psi-mi:“MI:0194”(cleavage reaction)	0.440
DPP4	VIP	psi-mi:“MI:0194”(cleavage reaction)	0.440
VIP	DPP4	psi-mi:“MI:0194”(cleavage reaction)	0.440
MEOX2	VIP	psi-mi:“MI:0915”(physical association)	0.370
VIP	LRP2	psi-mi:“MI:0914”(association)	0.350
VIP	VGF	psi-mi:“MI:0914”(association)	0.350
VIP	VHL	psi-mi:“MI:0914”(association)	0.350
VIP	UBQLN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): VIP (Two-hybrid), VIP (Two-hybrid), ACTBL2 (Affinity Capture-MS), PXDN (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), LRP2 (Affinity Capture-MS), VIP (Two-hybrid), CTNNA3 (Two-hybrid), UBQLN2 (Two-hybrid), VIP (Biochemical Activity), LRP2 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), PXDN (Affinity Capture-MS), KLHL13 (Affinity Capture-MS)

ESM2 similar proteins: A0JMK6, A5A6J6, B9WZ56, C0HKY1, C0HM54, E1ZXU8, O12956, O35314, O35417, O70176, P01165, P01282, P01362, P05060, P05408, P06300, P06308, P10362, P12285, P12961, P13521, P13589, P16014, P16613, P17685, P17686, P18509, P18844, P20616, P23389, P27682, P30945, P41534, P41535, P41585, P45644, P48143, P48144, P81401, P85799

Diamond homologs: C6EVG1, C6EVG2, O70176, P01282, P01283, P04203, P04204, P0DJ94, P0DJ95, P13589, P16613, P18509, P20394, P26349, P32648, P39089, P41535, P45644, P48143, P48144, P63289, P63290, P63291, P81039, P81401, P84488, P84771, P84772, Q29W19, P01284, P04566, P32649, P41534, P41585, P42692, P63292, Q09169, Q60549, P07217, P09916

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
VIP	up-regulates	VIPR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

783 predictions. Top by Δscore:

Variant	Effect	Δscore
6:152750955:GCGAG:G	donor_gain	1.0000
6:152750956:CGAG:C	donor_gain	1.0000
6:152750957:GAG:G	donor_gain	1.0000
6:152750957:GAGG:G	donor_gain	1.0000
6:152750957:GAGGT:G	donor_loss	1.0000
6:152750958:AG:A	donor_gain	1.0000
6:152750958:AGGT:A	donor_loss	1.0000
6:152750959:GG:G	donor_gain	1.0000
6:152750959:GGT:G	donor_loss	1.0000
6:152750960:G:GG	donor_gain	1.0000
6:152750960:GT:G	donor_loss	1.0000
6:152752166:A:AG	acceptor_gain	1.0000
6:152752167:G:GG	acceptor_gain	1.0000
6:152752167:GA:G	acceptor_gain	1.0000
6:152754161:A:AG	acceptor_gain	1.0000
6:152754161:ATCAG:A	acceptor_gain	1.0000
6:152754164:A:AG	acceptor_gain	1.0000
6:152754164:AG:A	acceptor_gain	1.0000
6:152754165:G:GG	acceptor_gain	1.0000
6:152754165:GG:G	acceptor_gain	1.0000
6:152754165:GGT:G	acceptor_gain	1.0000
6:152754165:GGTT:G	acceptor_gain	1.0000
6:152754285:CCAGG:C	donor_loss	1.0000
6:152754289:G:GG	donor_gain	1.0000
6:152754289:GTGA:G	donor_loss	1.0000
6:152754290:T:G	donor_loss	1.0000
6:152755261:T:TA	acceptor_gain	1.0000
6:152755267:A:AG	acceptor_gain	1.0000
6:152755268:G:GT	acceptor_gain	1.0000
6:152755268:GA:G	acceptor_gain	1.0000

AlphaMissense

1114 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:152756186:T:C	F130L	0.998
6:152756187:T:C	F130S	0.998
6:152756187:T:G	F130C	0.998
6:152756188:C:A	F130L	0.998
6:152756188:C:G	F130L	0.998
6:152756238:T:C	L147S	0.998
6:152756222:G:C	A142P	0.997
6:152756190:C:T	T131I	0.996
6:152756205:G:C	R136P	0.996
6:152756212:A:C	R138S	0.996
6:152756212:A:T	R138S	0.996
6:152756217:A:C	Q140P	0.995
6:152756168:C:A	R124S	0.994
6:152756223:C:A	A142D	0.994
6:152756180:G:C	A128P	0.993
6:152756198:T:G	Y134D	0.993
6:152756208:T:C	L137P	0.993
6:152756243:T:C	S149P	0.993
6:152756250:T:C	L151P	0.993
6:152756234:T:G	Y146D	0.992
6:152756235:A:G	Y146C	0.991
6:152756211:G:C	R138T	0.990
6:152755294:T:C	F86L	0.989
6:152755295:T:G	F86C	0.989
6:152755296:C:A	F86L	0.989
6:152755296:C:G	F86L	0.989
6:152755334:C:A	A99D	0.989
6:152756169:G:C	R124P	0.989
6:152756177:G:C	D127H	0.989
6:152755295:T:C	F86S	0.988

dbSNP variants (sampled 300 via entrez): RS1000049427 (6:152753681 G>C), RS1000112823 (6:152755977 T>A), RS1000185359 (6:152755692 G>A), RS1000277388 (6:152759765 AT>A,ATT), RS1000390378 (6:152749834 G>C,T), RS1000564258 (6:152760002 T>C), RS1001339028 (6:152756434 T>A), RS1001487256 (6:152750350 A>G), RS1001513572 (6:152750253 G>C), RS1001875270 (6:152756744 T>C), RS1002450693 (6:152755400 A>C), RS1002745773 (6:152754941 A>T), RS1002943222 (6:152751918 C>G,T), RS1002958402 (6:152758075 C>A,G), RS1003145187 (6:152758246 G>A)

Disease associations

OMIM: gene MIM:192320 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Asperger syndrome	Limited	Autosomal dominant

Mondo (1): (MONDO:0005259)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003429_28	Morning vs. evening chronotype	4.000000e-11
GCST005951_154	Body mass index	1.000000e-09
GCST007565_142	Morning person	4.000000e-33
GCST007576_1	Chronotype	4.000000e-33
GCST007576_423	Chronotype	9.000000e-30

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5737 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

16 measured of 18 human assays (66 total across all organisms); most potent 16 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
VIP Ala9	KI	0.29 nM
VIP Ala19	KI	0.59 nM
VIP [D-Asn9]	KI	1.1 nM
VIP [D-Ala4]	KI	1.1 nM
VIP Ala15	KI	2.1 nM
CAS_150828-75-4	KI	3.4 nM
VIP [D-Tyr10]	KI	3.7 nM
PACAP-VIP	KI	8 nM
[Ser9,Tyr13]VIP	KI	15 nM
VIP [D-Met17]	KI	29.5 nM
[Tyr13]VIP	KI	40 nM
[Ser9]VIP	KI	50 nM
VIP-PACAP	KI	100 nM
VIP [D-Asp8]	KI	110 nM
VIP [D-Thr7]	KI	162 nM
SR 147778	KI	1000 nM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	decreases expression, affects binding, increases expression, affects cotreatment	2
fenamic acid	increases expression, increases reaction	1
8-((4-chlorophenyl)thio)cyclic-3’,5’-AMP	increases expression	1
sodium arsenite	increases expression	1
nickel chloride	affects cotreatment, increases secretion, increases expression	1
N-(2-aminoethyl)-5-isoquinolinesulfonamide	decreases reaction, increases expression	1
5-nitro-2-(3-phenylpropylamino)benzoic acid	increases expression, increases reaction	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cyclic AMP	affects binding, increases abundance	1
Aspirin	increases expression	1
Atrazine	decreases expression	1
Bromocriptine	decreases reaction, increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Curcumin	decreases reaction, increases activity, increases expression	1
Doxorubicin	decreases expression	1
Progesterone	increases abundance	1
Silver	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019022	Binding	Binding affinity to vasoactive intestinal peptide	Bioactive Prenylhydroquinone Sulfates and a Novel C 31 Furanoterpene Alcohol Sulfate from the Marine Sponge, Ircinia Sp. — J Nat Prod

Clinical trials (associated diseases)

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