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Transient receptor potential cation channel, subfamily V, member 4
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM605427 MGI1926945 HomoloGene11003 IUPHAR: TRPV4 ChEMBL: 3119 GeneCards: TRPV4 Gene
RNA expression pattern
PBB GE TRPV4 219516 at tn.png
More reference expression data
Species Human Mouse
Entrez 59341 63873
Ensembl ENSG00000111199 ENSMUSG00000014158
UniProt Q9HBA0 Q9EPK8
RefSeq (mRNA) NM_001177428 NM_022017
RefSeq (protein) NP_001170899 NP_071300
Location (UCSC) Chr 12:
110.22 – 110.27 Mb
Chr 5:
114.62 – 114.66 Mb
PubMed search [1] [2]

Transient receptor potential cation channel subfamily V member 4 is a protein that in humans is encoded by the TRPV4 gene.[1][1][2][2][3]

This gene encodes TRPV4, a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels.[3][4][5] The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure.[6] Two transcript variants encoding different isoforms have been found for this gene.[7]

Clinical significance[edit]

Mutations in the TRPV4 gene are associated with a range of disorders, including brachyolmia type 3, congenital distal spinal muscular atrophy, scapuloperoneal spinal muscular atrophy and subtype 2C of Charcot–Marie–Tooth disease.[8]


A number of TRPV4 agonists and antagonists have been identified in the past ten years.[9] The discovery of unselective modulators (e.g. antagonist Ruthenium Red) was followed by the apparition of more potent (agonist 4aPDD)[10] or selective (antagonist RN-1734)[11] compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A[12] (with ~10 fold selectivity vs TRPV1) and antagonist HC-067047[13] (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8).


TRPV4 has been shown to interact with MAP7[14] and LYN.[15]

See also[edit]


  1. ^ a b Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant T (Dec 2000). "OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity". Nat. Cell Biol. 2 (10): 695–702. doi:10.1038/35036318. PMID 11025659. 
  2. ^ a b Liedtke W, Choe Y, Martí-Renom M, Bell A, Denis C, Sali A et al. (Nov 2000). "Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor". Cell 103 (3): 525–35. doi:10.1016/S0092-8674(00)00143-4. PMC 2211528. PMID 11081638. 
  3. ^ a b Clapham D, Julius D, Montell C, Schultz G (Dec 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. 
  4. ^ Harteneck C, Plant T, Schultz G (April 2000). "From worm to man: three subfamilies of TRP channels". Trends Neurosci. 23 (4): 159–66. doi:10.1016/S0166-2236(99)01532-5. PMID 10717675. 
  5. ^ Plant T, Strotmann R (2007). "TRPV4". Handb Exp Pharmacol 179 (179): 189–205. doi:10.1007/978-3-540-34891-7_11. PMID 17217058. 
  6. ^ Harteneck C, Reiter B (February 2007). "TRP channels activated by extracellular hypo-osmoticity in epithelia". Biochem. Soc. Trans. 35 (Pt 1): 91–5. doi:10.1042/BST0350091. PMID 17233610. 
  7. ^ "Entrez Gene: TRPV4 transient receptor potential cation channel, subfamily V, member 4". 
  8. ^ Online 'Mendelian Inheritance in Man' (OMIM) 605427
  9. ^ Vincent F, Duncton M (2011). "TRPV4 agonists and antagonists". Curr Top Med Chem 11 (17): 2216–26. PMID 21671873. 
  10. ^ Watanabe H, Davis J, Smart D, Jerman J, Smith G, Hayes P et al. (April 2002). "Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives". J. Biol. Chem. 277 (16): 13569–77. doi:10.1074/jbc.M200062200. PMID 11827975. 
  11. ^ Vincent F, Acevedo A, Nguyen M, Dourado M, DeFalco J, Gustafson A et al. (November 2009). "Identification and characterization of novel TRPV4 modulators". Biochem. Biophys. Res. Commun. 389 (3): 490–4. doi:10.1016/j.bbrc.2009.09.007. PMID 19737537. 
  12. ^ Thorneloe K, Sulpizio A, Lin Z, Figueroa D, Clouse A, McCafferty G et al. (August 2008). "N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I". J. Pharmacol. Exp. Ther. 326 (2): 432–42. doi:10.1124/jpet.108.139295. PMID 18499743. 
  13. ^ Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert J et al. (November 2010). "Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis". Proc. Natl. Acad. Sci. U.S.A. 107 (44): 19084–9. doi:10.1073/pnas.1005333107. PMC 2973867. PMID 20956320. 
  14. ^ Suzuki M, Hirao A, Mizuno A (December 2003). "Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)". J. Biol. Chem. 278 (51): 51448–53. doi:10.1074/jbc.M308212200. PMID 14517216. 
  15. ^ Xu H, Zhao H, Tian W, Yoshida K, Roullet J, Cohen D (Mar 2003). "Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress". J. Biol. Chem. 278 (13): 11520–7. doi:10.1074/jbc.M211061200. PMID 12538589. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.