TRPV5

Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the TRPV5 gene.^[5][6][7]

TRPV5
Identifiers
Aliases	TRPV5, CAT2, ECAC1, OTRPC3, transient receptor potential cation channel subfamily V member 5
External IDs	OMIM: 606679; MGI: 2429764; HomoloGene: 10520; GeneCards: TRPV5; OMA:TRPV5 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q34 Start 142,908,101 bp[1] End 142,933,746 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 B2.1 Start 41,629,107 bp[2] End 41,657,703 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in C1 segment human kidney substantia nigra blood corpus callosum hippocampus proper primary visual cortex Temporal Lobe Amygdala duodenum Top expressed in blastocyst right kidney morula human kidney vasculature vasculature of organ spinal cord embryo Temporal Lobe Amygdala More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ion channel activity protein binding calmodulin binding metal ion binding calcium channel activity Cellular component integral component of membrane plasma membrane integral component of plasma membrane membrane apical plasma membrane Biological process ion transport protein tetramerization calcium ion transport transmembrane transport regulation of urine volume calcium ion homeostasis calcium ion transmembrane transport calcium ion import across plasma membrane protein homotetramerization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56302 194352 Ensembl ENSG00000274348 ENSG00000127412 ENSMUSG00000036899 UniProt Q9NQA5 P69744 RefSeq (mRNA) NM_019841 NM_001007572 RefSeq (protein) NP_062815 NP_001007573 Location (UCSC) Chr 7: 142.91 – 142.93 Mb Chr 6: 41.63 – 41.66 Mb PubMed search [3] [4]
Wikidata
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Function

The TRPV5 gene is a member of the transient receptor family and the TRPV subfamily. The calcium-selective channel, TRPV5, encoded by this gene has 6 transmembrane-spanning domains, multiple potential phosphorylation sites, an N-linked glycosylation site, and 5 ANK repeats. This protein forms homotetramers or heterotetramers and is activated by a low internal calcium level.^[8]

Both TRPV5 and TRPV6 are expressed in kidney and intestinal epithelial cells.^[9] TRPV5 is mainly expressed in kidney epithelial cells, where it plays an important role in the reabsorption of Ca²⁺,^[10] whereas TRPV6 is mainly expressed in the intestine.^[9] The enzyme α-klotho increases kidney calcium reabsorption by stabilizing TPRV5.^[9] Klotho is a beta-glucuronidase-like enzyme that activates TRPV5 by removal of sialic acid.^[11]

Clinical significance

Normally, about 95% to 98% of Ca²⁺ filtered from the blood by the kidney is reabsorbed by the kidney's renal tubule, mediated by TRPV5.^[12] Genetic deletion of TRPV5 in mice leads to Ca²⁺ loss in the urine, and consequential hyperparathyroidism, and bone loss.^[13]

Autosomal recessive hypercalciuria has been described in a family with a missense, inactivating genetic variant in TRPV5. This variant, known as p.(Val598Met), affects the TRP helix region of TRPV5, which is thought to control channel pore gating, assembly and protein folding.^[14]

Inhibitors

• Econazole is a weak inhibitor of both TRPV5 and TRPV6, with an IC₅₀ in the micromolar range
• ZINC17988990 is a potent and selective inhibitor of TRPV5, with an IC₅₀ of 177nM and good selectivity over TRPV6 and the other TRPV channel subtypes.^[15]

Interactions

TRPV5 has been shown to interact with S100A10.^[16]

See also

• TRPV