Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC57YC6)

• DOT Name: Transient receptor potential cation channel subfamily V member 3 (TRPV3)
• Synonyms: TrpV3; Vanilloid receptor-like 3; VRL-3
• Gene Name: TRPV3
• Related Disease:
  Obsolete mutilating palmoplantar keratoderma with periorificial keratotic plaques
  Olmsted syndrome 1
  Isolated focal non-epidermolytic palmoplantar keratoderma
• UniProt ID: TRPV3_HUMAN
• PDB ID: 6H9J; 6HA6; 6MHO; 6MHS; 6MHV; 6MHW; 6MHX; 6OT2; 6OT5; 6UW4; 6UW6; 6UW8; 6UW9; 7QQN; 7XJ0; 7XJ1; 7XJ2; 7XJ3; 8GKA; 8GKG
• Pfam ID: PF00023 ; PF12796 ; PF00520
• Sequence:
  MKAHPKEMVPLMGKRVAAPSGNPAILPEKRPAEITPTKKSAHFFLEIEGFEPNPTVAKTS
  PPVFSKPMDSNIRQCISGNCDDMDSPQSPQDDVTETPSNPNSPSAQLAKEEQRRKKRRLK
  KRIFAAVSEGCVEELVELLVELQELCRRRHDEDVPDFLMHKLTASDTGKTCLMKALLNIN
  PNTKEIVRILLAFAEENDILGRFINAEYTEEAYEGQTALNIAIERRQGDIAALLIAAGAD
  VNAHAKGAFFNPKYQHEGFYFGETPLALAACTNQPEIVQLLMEHEQTDITSRDSRGNNIL
  HALVTVAEDFKTQNDFVKRMYDMILLRSGNWELETTRNNDGLTPLQLAAKMGKAEILKYI
  LSREIKEKRLRSLSRKFTDWAYGPVSSSLYDLTNVDTTTDNSVLEITVYNTNIDNRHEML
  TLEPLHTLLHMKWKKFAKHMFFLSFCFYFFYNITLTLVSYYRPREEEAIPHPLALTHKMG
  WLQLLGRMFVLIWAMCISVKEGIAIFLLRPSDLQSILSDAWFHFVFFIQAVLVILSVFLY
  LFAYKEYLACLVLAMALGWANMLYYTRGFQSMGMYSVMIQKVILHDVLKFLFVYIVFLLG
  FGVALASLIEKCPKDNKDCSSYGSFSDAVLELFKLTIGLGDLNIQQNSKYPILFLFLLIT
  YVILTFVLLLNMLIALMGETVENVSKESERIWRLQRARTILEFEKMLPEWLRSRFRMGEL
  CKVAEDDFRLCLRINEVKWTEWKTHVSFLNEDPGPVRRTDFNKIQDSSRNNSKTTLNAFE
  EVEEFPETSV
• Function: Putative receptor-activated 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. 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).
• 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).
• KEGG Pathway: Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway: TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsolete mutilating palmoplantar keratoderma with periorificial keratotic plaques	DIST2Y4B	Strong	Autosomal dominant	[1]
Olmsted syndrome 1	DISEJ1YA	Strong	Autosomal dominant	[2]
Isolated focal non-epidermolytic palmoplantar keratoderma	DISR6U95	Supportive	Autosomal dominant	[3]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[9]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[5]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[7]
Camphor	DMWIO46	Approved	Camphor increases the activity of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[10]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[11]
1,4-Naphthoquinone	DMTCMH7	Investigative	1,4-Naphthoquinone increases the activity of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[12]
1,2-NAPHTHOQUINONE	DMYXELH	Investigative	1,2-NAPHTHOQUINONE increases the activity of Transient receptor potential cation channel subfamily V member 3 (TRPV3).	[12]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome. Am J Hum Genet. 2012 Mar 9;90(3):558-64. doi: 10.1016/j.ajhg.2012.02.006.
• [3] A gain-of-function mutation in TRPV3 causes focal palmoplantar keratoderma in a Chinese family. J Invest Dermatol. 2015 Mar;135(3):907-909. doi: 10.1038/jid.2014.429. Epub 2014 Oct 6.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels. Pain. 2011 May;152(5):1156-1164. doi: 10.1016/j.pain.2011.01.044. Epub 2011 Feb 24.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [12] Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity. Chem Res Toxicol. 2018 May 21;31(5):291-301. doi: 10.1021/acs.chemrestox.7b00336. Epub 2018 Apr 30.