TRPV3

Summary

TRPV3 (transient receptor potential cation channel subfamily V member 3, HGNC:18084) is a protein-coding gene on chromosome 17p13.2, encoding Transient receptor potential cation channel subfamily V member 3 (Q8NET8). Non-selective calcium permeant cation channel.

This gene product belongs to a family of nonselective cation channels that function in a variety of processes, including temperature sensation and vasoregulation. The thermosensitive members of this family are expressed in subsets of sensory neurons that terminate in the skin, and are activated at distinct physiological temperatures. This channel is activated at temperatures between 22 and 40 degrees C. This gene lies in close proximity to another family member gene on chromosome 17, and the two encoded proteins are thought to associate with each other to form heteromeric channels. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 162514 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mutilating palmoplantar keratoderma with periorificial keratotic plaques (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 405 total — 9 pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_145068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18084
Approved symbol	TRPV3
Name	transient receptor potential cation channel subfamily V member 3
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	VRL3
Ensembl gene	ENSG00000167723
Ensembl biotype	protein_coding
OMIM	607066
Entrez	162514

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000301365, ENST00000381913, ENST00000571005, ENST00000571139, ENST00000572519, ENST00000573539, ENST00000574773, ENST00000575865, ENST00000576742, ENST00000577016, ENST00000616411, ENST00000898643, ENST00000898644

RefSeq mRNA: 2 — MANE Select: NM_145068 NM_001258205, NM_145068

CCDS: CCDS11029, CCDS58500

Canonical transcript exons

ENST00000576742 — 18 exons

Exon	Start	End
ENSE00001239301	3557676	3557812
ENSE00002656431	3510502	3514011
ENSE00002692655	3554732	3554852
ENSE00003472013	3526854	3526927
ENSE00003481719	3518576	3518850
ENSE00003504824	3532657	3532937
ENSE00003523457	3543474	3543628
ENSE00003539520	3514593	3514672
ENSE00003549930	3528025	3528126
ENSE00003551924	3530027	3530203
ENSE00003566987	3528837	3528995
ENSE00003579274	3516457	3516569
ENSE00003579994	3535573	3535713
ENSE00003608347	3524198	3524363
ENSE00003625274	3542522	3542698
ENSE00003685319	3544579	3544665
ENSE00003685624	3545167	3545271
ENSE00003692280	3520973	3521039

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 83.21.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8046 / max 68.9155, expressed in 559 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163852	0.9184	250
163850	0.2852	139
163847	0.2009	80
163851	0.1814	70
163849	0.1474	79
163848	0.0712	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	83.21	gold quality
skin of abdomen	UBERON:0001416	82.96	gold quality
sural nerve	UBERON:0015488	81.11	gold quality
tibial nerve	UBERON:0001323	79.50	gold quality
zone of skin	UBERON:0000014	78.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.14	gold quality
bone marrow cell	CL:0002092	72.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.33	gold quality
right frontal lobe	UBERON:0002810	71.02	gold quality
rectum	UBERON:0001052	70.92	gold quality
gastrocnemius	UBERON:0001388	70.64	gold quality
apex of heart	UBERON:0002098	70.43	gold quality
putamen	UBERON:0001874	70.15	gold quality
spinal cord	UBERON:0002240	69.88	gold quality
amygdala	UBERON:0001876	69.50	gold quality
caudate nucleus	UBERON:0001873	69.21	gold quality
right testis	UBERON:0004534	69.07	gold quality
nucleus accumbens	UBERON:0001882	69.02	gold quality
muscle of leg	UBERON:0001383	68.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.98	gold quality
granulocyte	CL:0000094	67.82	gold quality
prefrontal cortex	UBERON:0000451	67.80	gold quality
anterior cingulate cortex	UBERON:0009835	67.33	gold quality
left testis	UBERON:0004533	66.96	gold quality
mucosa of transverse colon	UBERON:0004991	66.84	gold quality
small intestine	UBERON:0002108	66.53	gold quality
testis	UBERON:0000473	65.69	gold quality
mucosa of stomach	UBERON:0001199	65.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

112 targeting TRPV3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4495	99.82	72.08	3080

Literature-anchored findings (GeneRIF, showing 40)

• member of the vanilloid channel family that is expressed in skin, tongue, dorsal root ganglion, trigeminal ganglion, spinal cord and brain; a calcium-permeable temperature-sensitive cation channel (PMID:12077604)
• temperature-sensitive (but capsaicin-insensitive) vanilloid receptor-like protein; may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels (PMID:12077606)
• accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG. (PMID:17521436)
• Ca(2+) inhibits TRPV3 from both the extracellular and intracellular sides. The inhibition is sequentially reduced, appearing as sensitization to repetitive stimulations. (PMID:18178557)
• 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)
• vanilloid type 3 (TRPV3) channel is crucially involved in pruritic dermatitis [review] (PMID:19209153)
• A multiligand binding site for ATP and calmodulin previously identified in the TRPV1 ankyrin repeat domain is conserved in TRPV3 and TRPV4, but not TRPV2. (PMID:19864432)
• Farnesyl pyrophosphate is the firstly identified endogenous TRPV3 activator that causes nociception (PMID:20395302)
• PI(4,5)P(2)-dependent modulation of TRPV3 activity represents an attractive mechanism for acute regulation of keratinocyte signaling cascades that control cell proliferation and the release of autocrine and paracrine factors. (PMID:21321070)
• TRPV3 channel is expressed in skin, its likely role is to detect noxious cold temperatures. (PMID:21490957)
• It was concluded that the sensitization of TRPV3 is intrinsic to the channel itself and occurs as a result of hysteresis of channel gating. (PMID:22006988)
• Nominal association was confirmed for TRPV3 rs7217270 in migraine with aura and TRPV1 rs222741 in the overall migraine group. (PMID:22162417)
• Nucleotide sequencing of five additional affected individuals also revealed missense mutations in TRPV3. (PMID:22405088)
• TRPV3 is a therapeutic target for itch (PMID:22475759)
• The Olmsted syndrome patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation with immunological dysregulation function. (PMID:23692804)
• TRPV3 has roles in skin physiology and in certain skin diseases [review] (PMID:23800054)
• Demonstrate similarities but also notable differences in TRPV3 pharmacology between recombinant and native systems. (PMID:23848361)
• TRPV3-ARD with characteristic finger 3 loop likely plays an important role in channel function and pharmacology. (PMID:24248473)
• TRPV3 missense mutation found in patient with Olmsted syndrome. (PMID:24452206)
• a TRPV3 mutation has a role in Olmsted syndrome [case report] (PMID:24463422)
• TPRV3 was significantly elevated in the epidermis of burn scars with pruritus. (PMID:24695993)
• A mutation in TRPV3 causes focal palmoplantar keratoderma in a Chinese family. (PMID:25285920)
• 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)
• Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. (PMID:25413349)
• Study illustrates the antiadipogenic role of TRPV3 in the adipocytes. (PMID:25774551)
• this study provides powerful tools to broaden our understanding of ligand interaction with TRPV channels, and the availability of purified human TRPV3 opens up perspectives for further structural and functional studies (PMID:25829496)
• TRPV3 missense mutation identified as a cause of the rare Olmsted syndrome. (PMID:26067147)
• these data suggest that TRPV3 sparklets cause dilation of cerebral parenchymal arterioles by activating IK and SK channels in the endothelium (PMID:26453324)
• A novel mutation in TRPV3 gene causes atypical familial Olmsted syndrome in a Chinese family. (PMID:26902751)
• High Transient receptor potential vanilloid 3 protein expression could promote the proliferation of lung cancer cells. Transient receptor potential vanilloid 3 inhibition decreased [Ca2+]i of lung cancer cells and cell cycle arrest at the G1/S boundary. (PMID:27023518)
• The results of the present study show that polymorphism of TRPV3 contributed towards symptom severity in FM. (PMID:27079220)
• *We describe two cases of Olmsted-like syndrome in a Mongolian family. *The underlying cause was a previously undescribed G573V point mutation in TRPV3. (PMID:27273692)
• TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes (PMID:27754757)
• Data indicate that the restoration of a single residue that is apparently missing in the use-dependent homologs could largely eliminate the use dependence of heat sensitivity of vanilloid receptor transient receptor potential 3 (TRPV3). (PMID:28154143)
• TRPV3 was highly expressed in the infiltrating eosinophils and mucosal epithelium of the nasal polyps of ECRS, and further that the more severe the refractoriness was after surgery, the higher the TRPV3 expression was in nasal polyps. (PMID:28462829)
• This study identified a direct regulatory effect of MBTPS2 on TRPV3 which can partially contribute to the overlapping clinical features of IFAP and Olmsted syndromes under a common signaling pathway. (PMID:28717930)
• 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)
• Study data show that TRPV3 is functionally expressed on human epidermal keratinocytes and that it plays a role in cutaneous inflammatory processes. (PMID:28964718)
• Data suggest that Thr264 in TRPV3 is key ERK1 phosphorylation site mediating EGFR-induced sensitization of TRPV3 to stimulate signaling pathways involved in regulating skin homeostasis. (TRPV3 = transient receptor potential cation channel subfamily V member-3; ERK1 = extracellular signal-regulated kinase-1; EGFR = epidermal growth factor receptor) (PMID:29084846)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trpv3	ENSMUSG00000043029
rattus_norvegicus	Trpv3	ENSRNOG00000019606
drosophila_melanogaster		FBGN0036414
drosophila_melanogaster	iav	FBGN0086693
caenorhabditis_elegans		WBGENE00003841
caenorhabditis_elegans		WBGENE00003889

Paralogs (5): TRPV4 (ENSG00000111199), TRPV5 (ENSG00000127412), TRPV6 (ENSG00000165125), TRPV2 (ENSG00000187688), TRPV1 (ENSG00000196689)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily V member 3 — Q8NET8 (reviewed: Q8NET8)

Alternative names: Vanilloid receptor-like 3

All UniProt accessions (5): A0A087X170, Q8NET8, I3L0L5, I3L402, J3KPJ6

UniProt curated annotations — full annotation on UniProt →

Function. Non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. The channel pore can dilate to provide permeability to larger cations. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen).

Subunit / interactions. Homotetramer. May convert from a homotetramer to a homopentamer to allow pore dilation. Interacts with TRPV1; may form a heteromeric channel with TRPV1. Interacts with SNX11; this interaction promotes TRPV3 trafficking from the cell membrane to lysosome for degradation.

Subcellular location. Cell membrane. Cytoplasm. Lysosome.

Tissue specificity. Abundantly expressed in CNS. Widely expressed at low levels. Detected in dorsal root ganglion (at protein level). Expressed in the keratinocyte layers of the outer root sheath and, to lesser extent, to the matrix of the hair follicles (at protein level).

Disease relevance. Olmsted syndrome 1 (OLMS1) [MIM:614594] An autosomal dominant, rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes. The disease is caused by variants affecting the gene represented in this entry. Palmoplantar keratoderma, non-epidermolytic, focal 2 (FNEPPK2) [MIM:616400] A dermatological disorder characterized by non-epidermolytic, abnormal thickening of the skin on the palms and soles. Focal palmoplantar keratoderma consists of localized areas of hyperkeratosis located mainly on pressure points and sites of recurrent friction. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by cannabinoid that binds to the vanilloid binding pocket. Diphenylboronic anhydride induces pore dilation and enhances cation permeability by promoting the conversion to a homopentamer.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV3 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NET8-1	1	yes
Q8NET8-2	2, A
Q8NET8-3	3, B

RefSeq proteins (2): NP_001245134, NP_659505* (*=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: PF00023, 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 (103 total): helix 35, strand 16, turn 9, topological domain 8, repeat 7, sequence variant 7, transmembrane region 6, mutagenesis site 4, region of interest 3, splice variant 3, chain 1, intramembrane region 1, compositionally biased region 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6H9J	X-RAY DIFFRACTION	1.83
6HA6	X-RAY DIFFRACTION	1.98
7QQN	X-RAY DIFFRACTION	2.45
8V6K	ELECTRON MICROSCOPY	2.46
7XJ0	ELECTRON MICROSCOPY	2.53
8GKA	ELECTRON MICROSCOPY	2.55
8V6N	ELECTRON MICROSCOPY	2.59
8V6O	ELECTRON MICROSCOPY	2.83
7XJ1	ELECTRON MICROSCOPY	2.93
6UW4	ELECTRON MICROSCOPY	3.1
9JDM	ELECTRON MICROSCOPY	3.13
6MHS	ELECTRON MICROSCOPY	3.2
9UED	ELECTRON MICROSCOPY	3.29
9BKU	ELECTRON MICROSCOPY	3.39
9JEG	ELECTRON MICROSCOPY	3.39
6MHO	ELECTRON MICROSCOPY	3.4
6MHV	ELECTRON MICROSCOPY	3.5
9JEE	ELECTRON MICROSCOPY	3.51
9JE5	ELECTRON MICROSCOPY	3.53
7XJ3	ELECTRON MICROSCOPY	3.54
6OT5	ELECTRON MICROSCOPY	3.6
9JEF	ELECTRON MICROSCOPY	3.62
8V6M	ELECTRON MICROSCOPY	3.63
7XJ2	ELECTRON MICROSCOPY	3.64
6UW6	ELECTRON MICROSCOPY	3.66
8V6L	ELECTRON MICROSCOPY	3.68
6MHW	ELECTRON MICROSCOPY	4
6MHX	ELECTRON MICROSCOPY	4
6UW8	ELECTRON MICROSCOPY	4.02
9DIJ	ELECTRON MICROSCOPY	4.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NET8-F1	76.84	0.38

Functional residue map

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

Ligand- & substrate-binding residues (1): 638

Mutagenesis-validated functional residues (4):

Position	Phenotype
557	impairs channel activation by tetrahydrocannabivarin.
560	impairs channel activation by tetrahydrocannabivarin.
561	impairs channel activation by tetrahydrocannabivarin.
563	impairs channel activation by tetrahydrocannabivarin.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 180 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, AP1_01, MYOGENIN_Q6, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_HAIR_CYCLE, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, CATTTCA_MIR203, GOBP_CALCIUM_ION_IMPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_REGULATION_OF_CALCIUM_ION_IMPORT, GOBP_ACTIN_FILAMENT_ORGANIZATION, BACH2_01, TGANTCA_AP1_C, GOBP_MOLTING_CYCLE

GO Biological Process (12): actin filament organization (GO:0007015), osmosensory signaling pathway (GO:0007231), response to temperature stimulus (GO:0009266), negative regulation of hair cycle (GO:0042636), calcium ion transmembrane transport (GO:0070588), positive regulation of calcium ion import (GO:0090280), calcium ion import across plasma membrane (GO:0098703), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (7): calcium channel activity (GO:0005262), sodium channel activity (GO:0005272), identical protein binding (GO:0042802), metal ion binding (GO:0046872), monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), lysosome (GO:0005764), plasma membrane (GO:0005886), cilium (GO:0005929), signaling receptor complex (GO:0043235), membrane (GO:0016020)

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
monoatomic cation transmembrane transport	2
calcium ion import	2
transport	2
monoatomic cation channel activity	2
cellular anatomical structure	2
actin cytoskeleton organization	1
supramolecular fiber organization	1
intracellular signal transduction	1
cellular response to osmotic stress	1
response to abiotic stimulus	1
hair cycle	1
regulation of hair cycle	1
negative regulation of multicellular organismal process	1
calcium ion 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
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
sodium ion transport	1
cellular process	1
calcium ion transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
protein binding	1
cation binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
binding	1
intracellular anatomical structure	1
lytic vacuole	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

830 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPV3	TRPM8	Q7Z2W7	972
TRPV3	ANK1	P16157	872
TRPV3	ANK3	Q12955	851
TRPV3	ANK2	Q01484	849
TRPV3	TRPM3	Q9HCF6	784
TRPV3	TRPM4	Q8TD43	743
TRPV3	TRPA1	O75762	742
TRPV3	TRPC5	Q9UL62	735
TRPV3	TRPM7	Q96QT4	726
TRPV3	TRPC1	P48995	709
TRPV3	TRPC3	Q13507	687
TRPV3	TRPC6	Q9Y210	681
TRPV3	TRPM6	Q9BX84	676
TRPV3	EGFR	P00533	662
TRPV3	CALM1	P02593	631

IntAct

93 interactions, top by confidence:

A	B	Type	Score
TRPV3	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	ERBIN	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV3	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (8): TRPV3 (Affinity Capture-Western), MMP15 (Affinity Capture-MS), NAT8L (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), RNF181 (Affinity Capture-MS), ULBP3 (Affinity Capture-MS), TRPV3 (Co-fractionation), TRPV3 (Co-fractionation)

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, Q810B6, Q9P2R3, P83757, Q03017

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPK3	“up-regulates activity”	TRPV3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	62.1×	5e-07
Unblocking of NMDA receptors, glutamate binding and activation	5	59.1×	5e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	5	59.1×	5e-07
Assembly and cell surface presentation of NMDA receptors	10	55.2×	1e-13
Dopamine Neurotransmitter Release Cycle	5	54.0×	7e-07
Long-term potentiation	5	51.7×	8e-07
Neurexins and neuroligins	11	47.1×	5e-14
Protein-protein interactions at synapses	7	40.4×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	81.7×	4e-13
protein localization to synapse	6	71.8×	2e-08
receptor clustering	7	68.3×	1e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	54.2×	6e-09
cell-cell adhesion	7	11.1×	2e-04
protein-containing complex assembly	5	8.9×	5e-03
chemical synaptic transmission	7	8.4×	7e-04
nervous system development	7	5.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	0
Uncertain significance	191
Likely benign	58
Benign	106

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
192257	NM_145068.4(TRPV3):c.1739A>C (p.Gln580Pro)	Pathogenic
2079284	NM_145068.4(TRPV3):c.1246C>T (p.Arg416Trp)	Pathogenic
30636	NM_145068.4(TRPV3):c.1717G>A (p.Gly573Ser)	Pathogenic
30637	NM_145068.4(TRPV3):c.1717G>T (p.Gly573Cys)	Pathogenic
30638	NM_145068.4(TRPV3):c.2074T>G (p.Trp692Gly)	Pathogenic
372610	NM_145068.4(TRPV3):c.1703G>A (p.Gly568Asp)	Pathogenic
391510	NM_145068.4(TRPV3):c.1718G>T (p.Gly573Val)	Pathogenic
4710292	NM_145068.4(TRPV3):c.1702G>T (p.Gly568Cys)	Pathogenic
803297	NM_145068.4(TRPV3):c.1703G>T (p.Gly568Val)	Pathogenic

SpliceAI

3127 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3516446:C:CA	donor_gain	1.0000
17:3518846:CAAGG:C	acceptor_gain	1.0000
17:3524314:C:CT	acceptor_gain	1.0000
17:3524318:C:CT	acceptor_gain	1.0000
17:3524321:G:GC	acceptor_gain	1.0000
17:3526852:A:AC	donor_gain	1.0000
17:3526853:C:CC	donor_gain	1.0000
17:3528020:CTTA:C	donor_loss	1.0000
17:3528021:TTAC:T	donor_loss	1.0000
17:3528022:TACCT:T	donor_loss	1.0000
17:3528023:A:AC	donor_gain	1.0000
17:3528023:AC:A	donor_gain	1.0000
17:3528023:ACCT:A	donor_gain	1.0000
17:3528024:C:A	donor_loss	1.0000
17:3528024:C:CC	donor_gain	1.0000
17:3528024:CC:C	donor_gain	1.0000
17:3528024:CCT:C	donor_gain	1.0000
17:3528024:CCTC:C	donor_gain	1.0000
17:3528122:ATGGC:A	acceptor_gain	1.0000
17:3528123:TGGC:T	acceptor_gain	1.0000
17:3528124:GGC:G	acceptor_gain	1.0000
17:3528125:GC:G	acceptor_gain	1.0000
17:3528126:CC:C	acceptor_gain	1.0000
17:3528127:C:CA	acceptor_loss	1.0000
17:3528127:C:CC	acceptor_gain	1.0000
17:3528130:C:CT	acceptor_gain	1.0000
17:3528832:CGTA:C	donor_loss	1.0000
17:3528833:GTA:G	donor_loss	1.0000
17:3528834:TA:T	donor_loss	1.0000
17:3528835:A:AC	donor_gain	1.0000

AlphaMissense

5238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3514654:C:A	W739C	1.000
17:3514654:C:G	W739C	1.000
17:3514656:A:G	W739R	1.000
17:3514656:A:T	W739R	1.000
17:3518634:A:G	L676P	1.000
17:3518648:G:C	N671K	1.000
17:3518648:G:T	N671K	1.000
17:3521013:G:C	F590L	1.000
17:3521013:G:T	F590L	1.000
17:3521015:A:G	F590L	1.000
17:3530121:C:T	G383E	1.000
17:3530122:C:G	G383R	1.000
17:3530122:C:T	G383R	1.000
17:3514645:C:A	W742C	0.999
17:3514645:C:G	W742C	0.999
17:3514647:A:G	W742R	0.999
17:3514647:A:T	W742R	0.999
17:3516566:C:G	A697P	0.999
17:3518587:A:G	W692R	0.999
17:3518587:A:T	W692R	0.999
17:3518630:C:A	M677I	0.999
17:3518630:C:G	M677I	0.999
17:3518630:C:T	M677I	0.999
17:3518637:G:T	A675D	0.999
17:3518643:A:G	L673P	0.999
17:3518652:A:G	L670P	0.999
17:3518655:A:G	L669P	0.999
17:3518658:A:C	L668R	0.999
17:3518658:A:G	L668P	0.999
17:3518658:A:T	L668H	0.999

dbSNP variants (sampled 300 via entrez): RS1000008917 (17:3516232 T>G), RS1000092337 (17:3545080 C>G,T), RS1000180267 (17:3518345 C>A), RS1000207047 (17:3552847 G>A), RS1000235126 (17:3510976 T>A), RS1000303358 (17:3546935 T>A), RS1000305225 (17:3529714 C>T), RS1000356717 (17:3547186 C>T), RS1000360851 (17:3513127 A>C), RS1000398845 (17:3540044 C>T), RS1000518681 (17:3559499 C>T), RS1000564642 (17:3520724 C>G), RS1000647396 (17:3512850 G>C), RS1000655735 (17:3529494 C>T), RS1000664749 (17:3557704 C>T)

Disease associations

OMIM: gene MIM:607066 | disease phenotypes: MIM:616400, MIM:614594

GenCC curated gene-disease

Disease	Classification	Inheritance
mutilating palmoplantar keratoderma with periorificial keratotic plaques	Strong	Autosomal dominant
Olmsted syndrome 1	Strong	Autosomal dominant
isolated focal non-epidermolytic palmoplantar keratoderma	Supportive	Autosomal dominant

Mondo (3): isolated focal non-epidermolytic palmoplantar keratoderma (MONDO:0014622), Olmsted syndrome 1 (MONDO:0100296), (MONDO:0019014)

Orphanet (2): Isolated focal non-epidermolytic palmoplantar keratoderma (Orphanet:448264), Mutilating palmoplantar keratoderma with periorificial keratotic plaques (Orphanet:659)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000157	Abnormality of the tongue
HP:0000164	Abnormality of the dentition
HP:0000168	Abnormality of the gingiva
HP:0000407	Sensorineural hearing impairment
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000970	Anhidrosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001036	Parakeratosis
HP:0001072	Thickened skin
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001371	Flexion contracture
HP:0001596	Alopecia
HP:0002164	Nail dysplasia
HP:0002289	Alopecia universalis
HP:0002797	Osteolysis
HP:0002861	Melanoma
HP:0003593	Infantile onset
HP:0005588	Patchy palmoplantar hyperkeratosis
HP:0007410	Palmoplantar hyperhidrosis
HP:0007460	Autoamputation of digits
HP:0007759	Opacification of the corneal stroma
HP:0007957	Corneal opacity
HP:0008069	Neoplasm of the skin
HP:0008070	Sparse hair
HP:0008392	Subungual hyperkeratosis

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5522 (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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7217270	TRPV3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (29 total), top 25:

Ligand	Action	Affinity	Parameter
farnesyl diphosphate	Activation	6.89	pEC50
isopentenyl diphosphate	Inhibition	6.62	pIC50
Trpvicin	Inhibition	6.42	pIC50
compound 74a [PMID: 27077528]	Antagonist	6.42	pIC50
aspirin-triggered resolvin D1	Inhibition	6.4	pIC50
forsythoside B	Inhibition	6.15	pIC50
14-Deoxy-11,12-didehydroandrographolide	Antagonist	6.1	pIC50
Isochlorogenic acid B	Inhibition	6.05	pIC50
ruthenium red	Inhibition	6.0	pIC50
Isochlorogenic acid A	Inhibition	5.57	pIC50
cannabidiol	Activation	5.43	pEC50
tetrahydrocannabivarin	Activation	5.42	pEC50
KS0365	Activation	5.29	pEC50
diphenyltetrahydrofuran	Antagonist	5.2	pIC50
Citrusinine II	Inhibition	4.91	pIC50
verbascoside	Inhibition	4.85	pIC50
incensole acetate	Activation	4.8	pEC50
2-APB	Full agonist	4.6	pEC50
osthole	Inhibition	4.4	pIC50
diphenylboronic anhydride	Full agonist	4.2	pEC50
6-tert-butyl-m-cresol	Activation	3.43	pEC50
thymol	Full agonist	3.3	pEC50
citral	Activation	3.03	pKd
dihydrocarveol	Activation	2.59	pEC50
carveol	Activation	2.52	pEC50

Binding affinities (BindingDB)

659 measured of 863 human assays (863 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-[3,5-dichloro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	1.45 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	1.68 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(S)-(2-(3-(3-chloropyridin-2-yloxy)pyrrolidin-1-yl)-5-(2-isopropylphenoxy)phenyl)methanol	IC50	2.01 nM	US-12435061: Compounds and compositions for use in treating skin disorders
2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)-N-[4-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	2.15 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)-N-[4-[2-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	2.21 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-5-yl)acetamide	IC50	2.49 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(S)-(2-(3-(3-chloropyridin-2-yloxy)pyrrolidin-1-yl)-5-(2-propylphenoxy)phenyl)methanol	IC50	2.65 nM	US-12435061: Compounds and compositions for use in treating skin disorders
(S)-(5-(2-ethylphenoxy)-2-(3-(3-methylpyridin-2-yloxy)pyrrolidin-1-yl)phenyl)methanol	IC50	2.8 nM	US-12435061: Compounds and compositions for use in treating skin disorders
N-[4-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	2.93 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	3.18 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-dichloro-4-(2-methylpropoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	3.34 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(3,3,3-trifluoropropyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	3.38 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3-chloro-5-fluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	3.54 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	3.63 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(S)-(2-(3-(3-chloropyridin-2-yloxy)pyrrolidin-1-yl)-5-(2-ethylphenoxy)phenyl)methanol	IC50	3.91 nM	US-12435061: Compounds and compositions for use in treating skin disorders
N-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(6-ethyl-1,3-dimethyl-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-5-yl)acetamide	IC50	3.98 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(3-(2’-cyclopropyl-3-(hydroxymethyl)biphenyl-4-yl)pyrrolidin-1-yl)(5-fluoropyridin-2-yl)methanone	IC50	3.99 nM	US-12435061: Compounds and compositions for use in treating skin disorders
N-[4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	4.02 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	4.16 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-N-[4-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	4.4 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	4.52 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[4-fluoro-3-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	4.84 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3-chloro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	5.29 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-N-[4-[2-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	5.29 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide	IC50	5.35 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4aH-quinazolin-1-ium-5-yl)acetamide	IC50	5.37 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(5-fluoropyridin-2-yl)(3-(3-(hydroxymethyl)-2’-isopropylbiphenyl-4-yl)pyrrolidin-1-yl)methanone	IC50	5.56 nM	US-12435061: Compounds and compositions for use in treating skin disorders
N-[4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide	IC50	5.6 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
4-[3-(3-methoxypropoxy)phenyl]-2-sulfanylidene-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5-one	IC50	5.61 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4aH-quinazolin-1-ium-5-yl)acetamide	IC50	5.96 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3-chloro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide	IC50	6.28 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4aH-quinazolin-1-ium-5-yl)acetamide	IC50	6.49 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	6.65 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-N-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	6.74 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4aH-pyrido[2,3-d]pyrimidin-1-ium-5-yl)acetamide	IC50	6.91 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	7.1 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
[5-(2-propan-2-ylphenoxy)-2-[(3S)-3-pyridin-2-yloxypyrrolidin-1-yl]phenyl]methanol	IC50	7.77 nM	US-12435061: Compounds and compositions for use in treating skin disorders
2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-N-[4-[3-fluoro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	8.04 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-[2-[(3S)-3-[(3-chloro-2-pyridinyl)oxy]pyrrolidin-1-yl]-5-(2-ethylphenoxy)phenyl]ethanol	IC50	8.27 nM	US-12435061: Compounds and compositions for use in treating skin disorders
(S)-(2-(3-(3-chloropyridin-2-yloxy)pyrrolidin-1-yl)-5-(p-tolyloxy)phenyl)methanol	IC50	8.42 nM	US-12435061: Compounds and compositions for use in treating skin disorders
N-[4-[3-chloro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	8.54 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(1,3-dimethyl-2,4-dioxo-4aH-pyrido[2,3-d]pyrimidin-1-ium-5-yl)-N-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	8.92 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[4-chloro-3-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	9.04 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(S)-(2-(3-(3-chloropyridin-2-yloxy)pyrrolidin-1-yl)-5-(2-fluorophenoxy)phenyl)methanol	IC50	9.39 nM	US-12435061: Compounds and compositions for use in treating skin disorders
2-(5,7-dimethyl-4,6-dioxo-2,3,3a,7a-tetrahydro-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-N-[4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	10.6 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3-fluoro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]-2-(2,5,7-trimethyl-4,6-dioxo-1,7a-dihydropyrazolo[3,4-d]pyrimidin-3-yl)acetamide	IC50	11 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(1,3-dimethyl-2,4-dioxo-4aH-quinazolin-1-ium-5-yl)-N-[4-[3-fluoro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	11.4 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
US9186360, 42	IC50	11.4 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(1,3-dimethyl-2,4-dioxo-4aH-pyrido[2,3-d]pyrimidin-1-ium-5-yl)-N-[4-[3-fluoro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	11.4 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)-N-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	11.9 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists

ChEMBL bioactivities

245 potent at pChembl≥5 of 258 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.10	IC50	80	nM	CHEMBL3696391
7.10	IC50	80	nM	CHEMBL3696410
6.96	IC50	110	nM	CHEMBL3692308
6.92	IC50	120	nM	CHEMBL3692305
6.92	IC50	120	nM	CHEMBL3696433
6.92	IC50	120	nM	CHEMBL3696452
6.89	IC50	130	nM	CHEMBL3696448
6.85	IC50	140	nM	CHEMBL3692284
6.85	IC50	140	nM	CHEMBL3692310
6.85	IC50	140	nM	CHEMBL3696392
6.85	IC50	140	nM	CHEMBL3696396
6.80	IC50	160	nM	CHEMBL3828278
6.80	IC50	160	nM	CHEMBL3696458
6.80	IC50	160	nM	CHEMBL3696407
6.80	IC50	160	nM	CHEMBL3696408
6.80	IC50	160	nM	CHEMBL3696409
6.77	IC50	170	nM	CHEMBL3696474
6.77	IC50	170	nM	CHEMBL3696426
6.77	IC50	170	nM	CHEMBL3696447
6.75	IC50	180	nM	CHEMBL3692282
6.75	IC50	180	nM	CHEMBL3696429
6.72	IC50	190	nM	CHEMBL3692275
6.72	IC50	190	nM	CHEMBL3696427
6.70	IC50	200	nM	CHEMBL3692233
6.66	IC50	220	nM	CHEMBL3696473
6.66	IC50	220	nM	CHEMBL3692279
6.64	IC50	230	nM	CHEMBL3692235
6.64	IC50	230	nM	CHEMBL3696418
6.64	IC50	230	nM	CHEMBL4115719
6.60	IC50	250	nM	CHEMBL3696439
6.58	IC50	260	nM	CHEMBL3692313
6.58	IC50	260	nM	CHEMBL3696434
6.58	IC50	260	nM	CHEMBL3696442
6.57	IC50	270	nM	CHEMBL3692304
6.55	IC50	280	nM	CHEMBL3696450
6.54	IC50	290	nM	CHEMBL3692261
6.54	IC50	290	nM	CHEMBL3692291
6.54	IC50	290	nM	CHEMBL3696403
6.54	IC50	290	nM	CHEMBL3696421
6.52	IC50	300	nM	CHEMBL3692297
6.52	IC50	300	nM	CHEMBL3696423
6.51	IC50	310	nM	CHEMBL3696384
6.50	IC50	320	nM	CHEMBL3692242
6.50	IC50	320	nM	CHEMBL3639911
6.50	IC50	320	nM	CHEMBL3692309
6.48	IC50	330	nM	CHEMBL3692262
6.48	IC50	330	nM	CHEMBL3692307
6.47	IC50	340	nM	CHEMBL3692306
6.47	IC50	340	nM	CHEMBL3696420
6.46	IC50	350	nM	CHEMBL3692312

PubChem BioAssay actives

17 with measured affinity, of 152 total; 11 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
(S)-[1-(3,4-dichlorophenyl)cyclobutyl]-pyridin-2-ylmethanol	1312382: Antagonist activity at human TRPV3 expressed in recombinant HEK293 cells assessed as inhibition of 2-APB induced calcium flux by FLIPR analysis	ic50	0.1600	uM
3-[(S)-hydroxy(pyridin-2-yl)methyl]-1-methyl-3-[4-(trifluoromethyl)-2-pyridinyl]cyclobutan-1-ol	1312346: Antagonist activity at human TRPV3 expressed in recombinant HEK293 cells assessed as inhibition of 2-APB induced currents by patch-clamp electrophysiological assay	ic50	0.3800	uM
4-[(E)-2-[(1R,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethenyl]-2H-furan-5-one	2112952: Inhibition of human TRPV3 expressed in CHO cells assessed as reduction in 2-APB induced channel current at -80 mV by whole-cell patch clamp electrophysiology	ic50	0.5600	uM
5,7-dihydroxy-2-(4-methoxyphenyl)chromen-4-one	2004670: Antagonist activity at human TRPV3 channel expressed in HEK293T cells assessed as inhibition of 2-APB induced channel current by whole cell patch clamp recordings	ic50	0.6200	uM
2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-pentylbenzene-1,3-diol	1845618: Agonist activity at ionomycin-stimulated TRPV3 (unknown origin) activation	ec50	1.0000	uM
6,6,9-trimethyl-3-propylbenzo[c]chromen-1-ol	1845620: Agonist activity at ionomycin-stimulated TRPV3 (unknown origin) channel desensitization in presence of carvacrol	ic50	1.6000	uM
2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-propylbenzene-1,3-diol	1845618: Agonist activity at ionomycin-stimulated TRPV3 (unknown origin) activation	ec50	1.7000	uM
2-methyl-2-(4-methylpent-3-enyl)-7-pentylchromen-5-ol	1845618: Agonist activity at ionomycin-stimulated TRPV3 (unknown origin) activation	ec50	1.9000	uM
(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol	1845620: Agonist activity at ionomycin-stimulated TRPV3 (unknown origin) channel desensitization in presence of carvacrol	ic50	3.0000	uM
6,6,9-trimethyl-3-pentylbenzo[c]chromen-1-ol	1845618: Agonist activity at ionomycin-stimulated TRPV3 (unknown origin) activation	ec50	5.3000	uM
[(2R,3R,4R,5R,6R)-2-[[(2R,3R,4R)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxymethyl]-6-[2-(3,4-dihydroxyphenyl)ethoxy]-5-hydroxy-4-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate	2112980: Inhibition of human TRPV3 expressed in HEK293 cells assessed as reduction in 2-APB induced channel current at voltage ramp from -100 to +100 mV by whole-cell patch clamp electrophysiology	ic50	6.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
carvacrol	increases activity, affects reaction, increases phosphorylation, increases response to substance	3
Smoke	increases activity, increases expression, increases response to substance	3
Benzo(a)pyrene	decreases methylation, affects methylation	2
aristolochic acid I	increases expression	1
Esketamine	increases expression	1
isopentenyl pyrophosphate	decreases reaction, increases activity	1
triphenyl phosphate	affects expression	1
cycloadiphenine	increases activity, increases response to substance	1
3,5-xylenol	increases activity	1
sodium arsenite	increases expression	1
tobacco tar	decreases reaction, increases expression	1
manganese chloride	decreases expression	1
creosol	increases activity	1
benzo(e)pyrene	increases methylation	1
2,4-dimethylphenol	increases activity	1
1-naphthol	increases activity	1
aflatoxin B2	increases methylation	1
1,4-naphthoquinone	increases activity	1
2,6-xylenol	increases activity	1
allyl sulfide	decreases reaction, increases expression	1
1,2-naphthoquinone	increases activity	1
4-ethylphenol	increases activity	1
2,5-xylenol	increases activity	1
2,3-dimethylphenol	increases activity	1
2,4-di-tert-butylphenol	increases activity	1
3,4-dimethylphenol	increases activity	1
2-aminoethoxydiphenyl borate	affects binding, increases activity	1
2-ethylphenol	increases activity	1
3-ethylphenol	increases activity	1
Sunitinib	decreases expression	1

ChEMBL screening assays

55 unique, capped per target: 52 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1118231	Functional	Antagonist activity at human TRPV3 channel	Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. — J Med Chem
CHEMBL1252946	Binding	Activation of TRPV3 in HEK cells assessed as increase in Ca2+ level from extracellular space at 300 uM	Nitric oxide activates TRP channels by cysteine S-nitrosylation. — Nat Chem Biol

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1KM	PrecisION hTRPV3-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07090889	PHASE1	RECRUITING	Study of KM-023 in Healthy Volunteers and Patients With Olmsted Syndrome.