TRPV2

Summary

TRPV2 (transient receptor potential cation channel subfamily V member 2, HGNC:18082) is a protein-coding gene on chromosome 17p11.2, encoding Transient receptor potential cation channel subfamily V member 2 (Q9Y5S1). Calcium-permeable, non-selective cation channel.

This gene encodes an ion channel that is activated by high temperatures above 52 degrees Celsius. The protein may be involved in transduction of high-temperature heat responses in sensory ganglia. It is thought that in other tissues the channel may be activated by stimuli other than heat.

Source: NCBI Gene 51393 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 106 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016113

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18082
Approved symbol	TRPV2
Name	transient receptor potential cation channel subfamily V member 2
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	VRL, VRL-1, VRL1
Ensembl gene	ENSG00000187688
Ensembl biotype	protein_coding
OMIM	606676
Entrez	51393

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000338560, ENST00000455666, ENST00000475513, ENST00000493434, ENST00000577277, ENST00000577865, ENST00000580788, ENST00000581560, ENST00000583241

RefSeq mRNA: 1 — MANE Select: NM_016113 NM_016113

CCDS: CCDS32576

Canonical transcript exons

ENST00000338560 — 15 exons

Exon	Start	End
ENSE00001384175	16422599	16422889
ENSE00001390499	16426099	16426269
ENSE00001505837	16427449	16427547
ENSE00001505838	16426722	16426877
ENSE00002725127	16415571	16415833
ENSE00002823967	16428317	16428387
ENSE00002855383	16431784	16431850
ENSE00002878594	16431966	16432300
ENSE00002961959	16433574	16433698
ENSE00003504951	16420115	16420248
ENSE00003614289	16417562	16417868
ENSE00003618191	16434890	16434969
ENSE00003656155	16428817	16428982
ENSE00003670238	16436789	16437003
ENSE00003789237	16423469	16423767

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 97.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1116 / max 323.3659, expressed in 1357 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159697	14.8169	1295
159700	4.9455	982
159698	4.6799	894
159699	3.6692	942

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.74	gold quality
upper lobe of left lung	UBERON:0008952	93.04	gold quality
upper lobe of lung	UBERON:0008948	92.38	gold quality
spleen	UBERON:0002106	92.19	gold quality
blood	UBERON:0000178	91.21	gold quality
right coronary artery	UBERON:0001625	90.81	gold quality
leukocyte	CL:0000738	90.66	gold quality
right lung	UBERON:0002167	90.59	gold quality
monocyte	CL:0000576	90.38	gold quality
mononuclear cell	CL:0000842	90.30	gold quality
right adrenal gland	UBERON:0001233	90.24	gold quality
right adrenal gland cortex	UBERON:0035827	89.69	gold quality
left coronary artery	UBERON:0001626	89.47	gold quality
left adrenal gland cortex	UBERON:0035825	89.35	gold quality
left adrenal gland	UBERON:0001234	89.14	gold quality
apex of heart	UBERON:0002098	89.09	gold quality
popliteal artery	UBERON:0002250	88.43	gold quality
tibial artery	UBERON:0007610	88.42	gold quality
coronary artery	UBERON:0001621	88.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.20	gold quality
omental fat pad	UBERON:0010414	87.88	gold quality
lymph node	UBERON:0000029	87.87	gold quality
peritoneum	UBERON:0002358	87.81	gold quality
adrenal cortex	UBERON:0001235	87.68	gold quality
adrenal gland	UBERON:0002369	87.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.25	gold quality
lung	UBERON:0002048	86.60	gold quality
vermiform appendix	UBERON:0001154	86.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.00	gold quality
stromal cell of endometrium	CL:0002255	85.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05
E-MTAB-5061	no	3.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting TRPV2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-6858-3P	96.37	64.41	771

Literature-anchored findings (GeneRIF, showing 40)

• TRPV2 and PKA have roles as a signaling module for transduction of physical stimuli in mast cells (PMID:15249591)
• It is concluded that PI3-kinase induces or modulates the activity of recombinant TRPV2 channels; in contrast to the previously proposed mechanism, activation of TRPV2 channels by PI3-kinase is not due to channel translocation to the plasma membrane. (PMID:16533525)
• Both TRPV1 and TRPV2 are found in human peripheral blood lymphocytes. (PMID:16777226)
• The TRPV2 ARD provides the first structural insight into a domain that coordinates nociceptive sensory transduction and is likely to be a prototype for other TRPV channel ARDs (PMID:16882997)
• A progressive loss of s-TRPV2 accompanied by an increase of hTRPV2 expression was found in high-grade and -stage UC. (PMID:17977643)
• Messenger RNA transcripts of TRPVs 1 through 4 are detected for the first time in human pulmonary artery smooth muscle cells. (PMID:18787888)
• relative gene expression ofTRPV1-4 in leukocytes is: TRPV3 < TRPV4, TRPV1 and TRPV2; leukocytes in hyposensitive subjects showed up-regulation of TRPV1, which was almost doubly expressed (PMID:18983665)
• The reduction of TRPV2 and TRPM8 immunoreactive nerve fibers in skin from individuals with Norrbottnian congenital insensitivity to pain further suggests that these ion channels are expressed primarily on nociceptive primary sensory neurons. (PMID:19482060)
• TRPV1-immunoreactivity was significantly higher and TRPV2-immunoreactivity was significantly lower in peripheral blood mononuclear cells from end-stage kidney disease patients compared to controls. (PMID:19619644)
• TRPV2 negatively controls glioma cell survival and proliferation, as well as resistance to Fas-induced apoptotic cell death in an ERK-dependent manner. (PMID:20093382)
• Findings establish a role for TRPV2 in PCa progression to the aggressive castration-resistant stage, prompting evaluation of TRPV2 as a potential prognostic marker and therapeutic target in the setting of advanced PCa. (PMID:20103638)
• TRPV2 plays a role in human hepatocarcinogenesis and might be a prognostic marker of patients with hepatocellular carcinoma (HCC). (PMID:20113837)
• A calmodulin binding site was located in the C-termini of TRPV2 (654-683) and TRPV5 (587-616). (PMID:20686800)
• Decrease in membrane phosphatidylinositol 4,5-bisphosphate (PIP2) levels on channel activation underlies a major component of divalent calcium ion-dependent desensitization of TRPV2 and may play a similar role in other TRP channels. (PMID:20926660)
• Human corneal epithelial cells possess thermosensitive TRPV2 activity. (PMID:21506114)
• TRPV2 plays a key role in mast-cell degranulation in response to mechanical, heat and red laser-light stimulation. (PMID:21574765)
• Cultivated HCjE cells and human conjunctiva express TRPV2, mRNA. (PMID:22327830)
• The increased expression of TRPV2 gene in peripheral lymphocytes is closely correlated with childhood asthma in the north of China. (PMID:23294145)
• Duchenne muscular dystrophy primary human myotubes exhibit abnormal elevation of TRPV2-dependant cation entry. (PMID:23426965)
• TRPV1 and TRPV2 are potential targets for potential therapeutic interventions in cardiovascular disease. (PMID:23453732)
• TRPV2-coupled signaling as a key player in mediating the cellular actions of heat shock on DCs (PMID:23542034)
• TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion. (PMID:23741410)
• Sarcolemmal TRPV2 accumulation appears to have considerable pathological impact on Dilated cardiomyopathy (DCM) progression. (PMID:23786999)
• The addition of TRPV2 inhibitor Tranilast in the incubation medium prevent the calcium influx triggered by lysoPC and reduced lysoPC-induced cytotoxicity,whereas TRPV4 inhibitor RN 1734 was without effect (PMID:23964684)
• An upregulation in the expression of vanilloid transient potential channels 2 enhances hypotonicity-induced cytosolic Ca(2) rise in human induced pluripotent stem cell model of Hutchinson-Gillford Progeria. (PMID:24475260)
• TRPV1-, TRPV2-, P2X3-, and parvalbumin-immunoreactivity neurons in the human nodose ganglion innervate the pharynx and epiglottis through the pharyngeal branch and superior laryngeal nerve (PMID:24764033)
• High expression of TRPV2 mRNA was closely associated with advanced pathological stage and worse survival of patients with esophageal squamous cell carcinoma. (PMID:24878697)
• Aim of this review is to study the role of the TRPV2 channel, a member of the TRPV subfamily of TRP channels, in tumor progression. [review] (PMID:25001513)
• Data indicate that transient receptor potential vanilloid 2 (TRPV2) siRNA virtually abolished stretch-activated current. (PMID:25268680)
• Using multiple sequence alignments as source for evolutionary, bioinformatics and statistical analysis, we have analyzed the evolutionary profiles for TRPV1, TRPV2, TRPV3 and TRPV4 (PMID:25333484)
• There appears to be TRPV1- or TRPV2-IR sympathetic pathway in the human stellate ganglion and spinal cord. (PMID:25641129)
• This study evaluated the role of Trpv2 in arthritis and the pharmacological effects of Trpv2 agonists. (PMID:25869297)
• transient receptor potential vanilloid 2 is an intracellular Ca(2+)-permeable transient receptor potential vanilloid channel upregulated by nerve growth factor via the mitogen-activated protein kinase signaling pathway to augment neurite outgrowth. (PMID:26416880)
• both TRPV2 and TRPV4 are involved in migration of human cardiac c-kit(+) progenitor cells. (PMID:26865051)
• High TRPV2 expression is associated with breast cancer. (PMID:26993604)
• The results of the study show that polymorphism of TRPV2 influenced the susceptibility to FM. (PMID:27079220)
• Binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. (PMID:27298359)
• CGRP- and TRPV2-containing trigeminal neurons probably innervate the paranasal sinus mucosae, and project into spinal and principal trigeminal sensory nuclei. (PMID:27553072)
• Study shows that despite lacking gastric mucosal inflammation, up-regulation of TRPV1 and TRPV2, down-regulation of BDNF were observed in functional dyspepsia (FD) patients. These suggest that immune alteration may contribute to the pathogenesis of FD without any previous infection. (PMID:28782273)
• the expression of transient receptor potential vanilloid-1 (TRPV1), transient receptor potential vanilloid-2 (TRPV2) and transient receptor potential vanilloid-3 (TRPV3) channels in native human odontoblasts, was examined. (PMID:28905239)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpv1	ENSDARG00000059883
mus_musculus	Trpv2	ENSMUSG00000018507
rattus_norvegicus	Trpv2	ENSRNOG00000003104
drosophila_melanogaster		FBGN0036414
drosophila_melanogaster	iav	FBGN0086693
caenorhabditis_elegans		WBGENE00003841
caenorhabditis_elegans		WBGENE00003889

Paralogs (5): TRPV4 (ENSG00000111199), TRPV5 (ENSG00000127412), TRPV6 (ENSG00000165125), TRPV3 (ENSG00000167723), TRPV1 (ENSG00000196689)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily V member 2 — Q9Y5S1 (reviewed: Q9Y5S1)

Alternative names: Osm-9-like TRP channel 2, Vanilloid receptor-like protein 1

All UniProt accessions (6): Q9Y5S1, H7BZK2, K7EIQ6, K7EKG5, K7ELL3, K7EPY7

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-permeable, non-selective cation channel. Seems to be regulated, at least in part, by growth factors, such as IGF1, PDGF and morphogenetic neuropeptide/head activator. May transduce physical stimuli in mast cells.

Subunit / interactions. Homotetramer. Interacts with a cAMP-dependent protein kinase type II regulatory subunit (PRKAR2A or PRKAR2B) and ACBD3. Interacts with SLC50A1; the interaction probably occurs intracellularly and depends on TRPV2 N-glycosylation.

Subcellular location. Cell membrane. Cytoplasm. Melanosome.

Post-translational modifications. N-glycosylated. Phosphorylated by PKA.

Activity regulation. Activated by temperatures higher than 52 degrees Celsius. Weakly activated by cannabinoid that binds to the vanilloid binding pocket; this activation is potentiated by the binding of uricosuric agents like probenecid.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV2 sub-subfamily.

RefSeq proteins (1): NP_057197* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR005821	Ion_trans_dom	Domain
IPR008347	TrpV1-4	Family
IPR024862	TRPV	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00520, PF12796

Catalyzed reactions (Rhea), 4 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (59 total): helix 17, sequence conflict 10, topological domain 7, transmembrane region 6, repeat 6, region of interest 4, modified residue 3, sequence variant 2, turn 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2F37	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5S1-F1	78.85	0.32

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): 6, 751, 763

Glycosylation sites (1): 570

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 267 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GGGTGGRR_PAX4_03, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, ONKEN_UVEAL_MELANOMA_UP

GO Biological Process (11): sensory perception (GO:0007600), response to temperature stimulus (GO:0009266), positive regulation of axon extension (GO:0045773), calcium ion transmembrane transport (GO:0070588), positive regulation of calcium ion import (GO:0090280), calcium ion import across plasma membrane (GO:0098703), positive regulation of cold-induced thermogenesis (GO:0120162), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (5): monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), calcium channel activity (GO:0005262), monoatomic ion transmembrane transporter activity (GO:0015075), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), cell surface (GO:0009986), growth cone membrane (GO:0032584), melanosome (GO:0042470), axonal growth cone (GO:0044295), cell body (GO:0044297), cytoplasm (GO:0005737), membrane (GO:0016020), axon (GO:0030424)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Stimuli-sensing channels	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
calcium ion import	2
transport	2
growth cone	2
nervous system process	1
response to abiotic stimulus	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
positive regulation of calcium ion transport	1
regulation of calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
transmembrane transporter activity	1
monoatomic ion transmembrane transport	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
pigment granule	1
intracellular anatomical structure	1
neuron projection	1

Protein interactions and networks

STRING

1154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPV2	TRPM8	Q7Z2W7	929
TRPV2	TRPA1	O75762	896
TRPV2	TRPM4	Q8TD43	846
TRPV2	TRPC1	P48995	844
TRPV2	TRPM3	Q9HCF6	822
TRPV2	ANK1	P16157	814
TRPV2	TRPM7	Q96QT4	791
TRPV2	ANK2	Q01484	790
TRPV2	TRPM5	Q9NZQ8	787
TRPV2	TRPC6	Q9Y210	761
TRPV2	MCOLN1	Q9GZU1	750
TRPV2	TRPC3	Q13507	746
TRPV2	TRPC4	Q9UBN4	737
TRPV2	TRPC5	Q9UL62	720
TRPV2	SERPINA6	P08185	684

IntAct

29 interactions, top by confidence:

A	B	Type	Score
S	ACE2	psi-mi:“MI:0914”(association)	1.000
S	TRPV2	psi-mi:“MI:0915”(physical association)	0.500
TRPV2	NTM	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	FGF1	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	ST18	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	ABR	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	KCNJ10	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	PEBP1	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	SLC44A2	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	OPALIN	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	CDH6	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	INPP5F	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	PIP4K2B	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	ARF1	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	PLP1	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	SDC3	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	CACNG3	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	PI16	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	SACM1L	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	SHISA6	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	ARL15	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	ALDH1A3	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
	FN1	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): TRPV2 (Affinity Capture-Western), TRPV2 (Proximity Label-MS), TRPV2 (Proximity Label-MS), TRPV2 (Proximity Label-MS), TRPV2 (Affinity Capture-MS), TRPV2 (Affinity Capture-MS), TRPV2 (Affinity Capture-MS), TRPV2 (Affinity Capture-RNA), TRPV2 (Affinity Capture-MS), TRPV2 (Affinity Capture-MS), TRPV2 (Protein-RNA)

ESM2 similar proteins: A0A1D5PXA5, O18784, O35119, O35433, O62852, P0C550, P19334, P34586, P34641, P48994, P48995, P69744, P79100, P97414, Q0JKV1, Q12324, Q5ICL9, Q61056, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q875M2, Q8GXE6, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q96L42, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9MYV9, Q9NQA5, Q9P2G1, Q9QUQ5, Q9QX01, Q9QX29

Diamond homologs: A0A1D5PXA5, O35433, P69744, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9NQA5, Q9R186, Q9WTR1, Q9WUD2, Q9XSM3, Q9Y5S1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2992 predictions. Top by Δscore:

Variant	Effect	Δscore
17:16415829:GCGGG:G	donor_gain	1.0000
17:16415831:GGG:G	donor_gain	1.0000
17:16415832:GG:G	donor_gain	1.0000
17:16415832:GGG:G	donor_gain	1.0000
17:16415833:GG:G	donor_gain	1.0000
17:16417558:GCAG:G	acceptor_loss	1.0000
17:16417560:A:AG	acceptor_gain	1.0000
17:16417561:G:C	acceptor_loss	1.0000
17:16417561:G:GG	acceptor_gain	1.0000
17:16417828:A:G	donor_gain	1.0000
17:16420112:CA:C	acceptor_loss	1.0000
17:16420113:A:AG	acceptor_gain	1.0000
17:16420113:A:AT	acceptor_loss	1.0000
17:16420114:G:GT	acceptor_gain	1.0000
17:16420114:GT:G	acceptor_gain	1.0000
17:16420114:GTC:G	acceptor_gain	1.0000
17:16420114:GTCA:G	acceptor_gain	1.0000
17:16420246:CAGG:C	donor_loss	1.0000
17:16422597:AGAG:A	acceptor_gain	1.0000
17:16422598:GAGG:G	acceptor_gain	1.0000
17:16422888:CGGTG:C	donor_loss	1.0000
17:16422891:T:A	donor_loss	1.0000
17:16423768:G:GC	donor_loss	1.0000
17:16423769:T:G	donor_loss	1.0000
17:16426882:GGGC:G	donor_gain	1.0000
17:16426883:GGCG:G	donor_gain	1.0000
17:16428388:G:GG	donor_gain	1.0000
17:16428392:G:GG	donor_gain	1.0000
17:16428978:AGAAG:A	donor_loss	1.0000
17:16428979:GAAG:G	donor_gain	1.0000

AlphaMissense

4959 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:16431808:T:C	F538L	0.997
17:16431810:C:A	F538L	0.997
17:16431810:C:G	F538L	0.997
17:16428914:T:A	W507R	0.996
17:16428914:T:C	W507R	0.996
17:16433577:G:C	A665P	0.994
17:16422856:T:C	F198L	0.992
17:16422858:C:A	F198L	0.992
17:16422858:C:G	F198L	0.992
17:16423490:C:A	A216D	0.992
17:16423469:G:T	G209V	0.991
17:16423745:C:A	A301D	0.991
17:16423748:C:A	A302D	0.991
17:16431841:T:C	F549L	0.991
17:16431843:C:A	F549L	0.991
17:16431843:C:G	F549L	0.991
17:16422780:G:C	E172D	0.990
17:16422780:G:T	E172D	0.990
17:16423469:G:A	G209D	0.990
17:16423493:C:A	A217D	0.990
17:16423526:T:C	L228P	0.990
17:16423742:T:C	L300P	0.990
17:16432246:G:A	M645I	0.990
17:16432246:G:C	M645I	0.990
17:16432246:G:T	M645I	0.990
17:16423478:C:A	P212H	0.989
17:16423581:C:A	N246K	0.989
17:16423581:C:G	N246K	0.989
17:16423716:C:A	N291K	0.989
17:16423716:C:G	N291K	0.989

dbSNP variants (sampled 300 via entrez): RS1000007923 (17:16437056 A>G), RS1000081388 (17:16425023 T>A,C), RS1000117071 (17:16418944 C>A), RS1000282934 (17:16430404 T>G), RS1000547162 (17:16429431 T>C), RS1000692405 (17:16435218 C>G), RS1000744704 (17:16429734 G>A), RS1000884669 (17:16428969 T>A,C,G), RS1000885901 (17:16423028 T>C,G), RS1001126594 (17:16417198 A>C,G), RS1001157057 (17:16436324 C>T), RS1001212454 (17:16428716 T>C), RS1001314569 (17:16429710 G>A), RS1001345393 (17:16424058 C>T), RS1001785525 (17:16430066 C>T)

Disease associations

OMIM: gene MIM:606676 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007001_11	Cerebrospinal AB1-42 levels in normal cognition	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5051 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,738 (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
CHEMBL74415	CANNABINOL	3	18,794
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884
CHEMBL2387742	CANNABIDIVARIN	2	4,963
CHEMBL497318	CANNABIGEROL	2	11,097

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
SET2	Channel blocker	6.34	pIC50
ruthenium red	Channel blocker	6.2	pIC50
loratadine	Inhibition	5.52	pIC50
tranilast	Inhibition	5.0	pIC50
Δ9-tetrahydrocannabinol	Activation	4.85	pEC50
cannabidiol	Activation	4.5	pEC50
probenecid	Activation	4.5	pEC50
cannabinol	Activation	4.11	pEC50
SKF96365	Channel blocker	4.0	pIC50
2-APB	Agonist	3.9	pEC50

ChEMBL bioactivities

8 potent at pChembl≥5 of 11 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.10	IC50	800	nM	TETRAHYDROCANNABIVARIN
5.82	IC50	1500	nM	CANNABIGEROL
5.77	EC50	1700	nM	CANNABIGEROL
5.66	IC50	2200	nM	CHEMBL4170268
5.51	EC50	3100	nM	CHEMBL4170268
5.39	EC50	4100	nM	TETRAHYDROCANNABIVARIN
5.19	IC50	6500	nM	CANNABICHROMENE
5.14	EC50	7300	nM	CANNABIDIVARIN

PubChem BioAssay actives

8 with measured affinity, of 26 total; 5 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
(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol	1845617: Agonist activity at ionomycin-stimulated TRPV2 (unknown origin) channel desensitization in presence of lysophosphatidylcholine	ic50	0.8000	uM
2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-pentylbenzene-1,3-diol	1845617: Agonist activity at ionomycin-stimulated TRPV2 (unknown origin) channel desensitization in presence of lysophosphatidylcholine	ic50	1.5000	uM
6,6,9-trimethyl-3-propylbenzo[c]chromen-1-ol	1845617: Agonist activity at ionomycin-stimulated TRPV2 (unknown origin) channel desensitization in presence of lysophosphatidylcholine	ic50	2.2000	uM
2-methyl-2-(4-methylpent-3-enyl)-7-pentylchromen-5-ol	1845617: Agonist activity at ionomycin-stimulated TRPV2 (unknown origin) channel desensitization in presence of lysophosphatidylcholine	ic50	6.5000	uM
2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-propylbenzene-1,3-diol	1845615: Agonist activity at ionomycin-stimulated TRPV2 (unknown origin) activation	ec50	7.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	3
bisphenol A	affects expression, affects cotreatment, decreases expression	2
cannabidiolic acid	increases expression, increases activity, increases uptake	2
(+)-JQ1 compound	decreases expression	2
Cannabidiol	increases activity, increases uptake	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
cannabichromene	increases uptake, increases activity	1
tranilast	decreases activity	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
cannabidivarin	increases activity, increases uptake	1
Zoledronic Acid	decreases expression	1
Amiodarone	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 10 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1224913	Functional	Agonist activity at TRPV2	Sensing with TRP channels. — Nat Chem Biol
CHEMBL3112351	Binding	Antagonist activity at human TRPV2 expressed in HEK293T cells assessed as LPC-induced intracellular Ca2+ influx at 100 uM by Fluo-4 AM staining-based fluorescence analysis	Activation and inhibition of thermosensitive TRP channels by voacangine, an alkaloid present in Voacanga africana, an African tree. — J Nat Prod

Cellosaurus cell lines

4 cell lines: 4 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7Q3	SEES3-1V human TRPV2, clone1	Embryonic stem cell	Male
CVCL_A7Q4	SEES3-1V human TRPV2, clone2	Embryonic stem cell	Male
CVCL_A7Q5	SEES3-1V human TRPV2, clone3	Embryonic stem cell	Male
CVCL_D6SB	WAe009-A-1Y	Embryonic stem cell	Female

Clinical trials (associated diseases)

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