TRPV6 (transient receptor potential cation channel, subfamily V, member 6)

2009-03-01   Yoshiro Suzuki , Matthias A Hediger 

Institute of Biochemistry, Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland


Atlas Image
Schematic representation of human TRPV6 gene and neighbouring genes.


Atlas Image
Genomic structure of human TRPV6. The coding region is shown by open bars. The non-translated regions are shown by filled bars.


TRPV6 gene consists of 15 exons and 14 introns including a coding, and a 5-/3- non-coding region. The regions encoding the ankyrin repeats, 6 transmembrane domains and a pore region are indicated. Several VDREs (vitamin D responsive element) have been identified in its promoter region.
A haplotype containing 3 non-synonymous polymorphisms (C157R+M378V+M681T) represent a recent positive selection in human evolution. The same haplotype seems to be associated with renal calcium stone formation.


There is an alterative splice variant which missed 25-192 (a.a.). In EST database, there seems to be at least one more variant using different exon 1 (V2) and a variant starting from another site (P3) just upstream of exon 2 (V3).


Atlas Image
Schematic representation of TRPV6 protein. Four subunits makes one channel pore. Several ankyrin repeats, one N-glycosylation site and several calmodulin binding sites (CaM) are indicated.


Glycosylated membrane protein (725 a.a., MW ~70 kDa) with 6 transmembrane regions and a pore-forming loop. N- and C-terminal tails are in cytoplasmic side. This protein forms a Ca2+-selective ion channel in the plasma membrane.
TRPV6 interacts with calmodulin which contribute to the intracellular Ca2+-dependent inactivation to avoid an increase of free Ca2+ concentration.
The ankyrin repeats may play a role in the interaction between subunits. TRPV6 can form a homo-tetramer as well as a hetero-tetramer with TRPV5, which exhibits distinct channel properties.


Highly expressed in placenta, moderately expressed in exocrine pancreas, mammary gland and salivary gland. Highly induced in small intestine under low calcium conditions or by 1,25-dihydroxyvitamin D3 treatment. Highly induced in prostate, breast and other cancer tissues during tumor progression.


Plasma membrane. Localized in the apical membrane of the epithelial cells in the duodenum, and syncytiotrophoblasts in placenta.


Apical Ca2+ entry pathway for total body calcium homeostasis in the small intestine under the control of 1,25-dihydroxyvitamin D3. TRPV6 likely also be involved in the placental Ca2+ transport from mother to fetus to maintain fetal bone mineralization.
TRPV6 may play a role in the Ca2+ entry pathway essential for keratinocyte differentiation. Although its exact function in cancer cells and tumor progression is still under investigation, TRPV6 is involved in an increase in proliferation and apoptotic resistance in cancer cells.


73% identity with human TRPV5. 89% identity with mouse TRPV6.

Implicated in

Entity name
Prostate cancer
Expression of TRPV6 may be a predictor for prostate cancer progression since TRPV6 mRNA and protein levels are elevated in prostatic carcinoma compared to benign prostatic hyperplasia and positively correlated with Gleason grade/score in prostatic carcinoma.
TRPV6 is involved in an increase in proliferation and apoptotic resistance in cancer cells, suggesting that TRPV6 could be a new therapeutic target for the treatment for advanced prostate cancer.
Entity name
Breast cancer
TRPV6 mRNA was also found to be increased in breast cancer tissues compared to normal breast tissues. TRPV6 could be a prognostic marker for breast cancer and therapeutic target for breast cancer treatment.


Pubmed IDLast YearTitleAuthors
167170582006TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations.Akey JM et al
171291782007Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene.Bianco SD et al
182456672008The role of TRPV6 in breast carcinogenesis.Bolanz KA et al
151920902004Ca2+-selective transient receptor potential V channel architecture and function require a specific ankyrin repeat.Erler I et al
145864122003Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression.Fixemer T et al
156184842005Calcium absorption across epithelia.Hoenderop JG et al
183017632008Parallel selection on TRPV6 in human populations.Hughes DA et al
175509012007TRPV6 is a Ca2+ entry channel essential for Ca2+-induced differentiation of human keratinocytes.Lehen'kyi V et al
165747382006The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells.Meyer MB et al
125063512003Calcium fluxes in human trophoblast (BeWo) cells: calcium channels, calcium-ATPase, and sodium-calcium exchanger expression.Moreau R et al
112481242001Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin.Niemeyer BA et al
120771272002Fast and slow inactivation kinetics of the Ca2+ channels ECaC1 and ECaC2 (TRPV5 and TRPV6). Role of the intracellular loop located between transmembrane segments 2 and 3.Nilius B et al
115493222001Structural conservation of the genes encoding CaT1, CaT2, and related cation channels.Peng JB et al
110978382000Human calcium transport protein CaT1.Peng JB et al
114015232001CaT1 expression correlates with tumor grade in prostate cancer.Peng JB et al
184455992008The human TRPV6 channel protein is associated with cyclophilin B in human placenta.Stumpf T et al
183486952008Calcium channel TRPV6 is involved in murine maternal-fetal calcium transport.Suzuki Y et al
178502112008Mechanisms and regulation of epithelial Ca2+ absorption in health and disease.Suzuki Y et al
182766102008Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation.Suzuki Y et al
116876342001Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects.Van Cromphaut SJ et al
112785792001Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer.Wissenbach U et al
124809252002Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies.Zhuang L et al

Other Information

Locus ID:

NCBI: 55503
MIM: 606680
HGNC: 14006
Ensembl: ENSG00000165125


dbSNP: 55503
ClinVar: 55503
TCGA: ENSG00000165125


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Salivary secretionKEGGko04970
Salivary secretionKEGGhsa04970
Mineral absorptionKEGGko04978
Mineral absorptionKEGGhsa04978
Transmembrane transport of small moleculesREACTOMER-HSA-382551
Ion channel transportREACTOMER-HSA-983712
Stimuli-sensing channelsREACTOMER-HSA-2672351
TRP channelsREACTOMER-HSA-3295583

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
156472882005A functional link between store-operated and TRPC channels revealed by the 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2.67
165747382006The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells.62
292582892018Opening of the human epithelial calcium channel TRPV6.55
117447522001Function and expression of the epithelial Ca(2+) channel family: comparison of mammalian ECaC1 and 2.50
147368892004Outer pore architecture of a Ca2+-selective TRP channel.38
126010872003Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6.36
228075782012Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer.33
120110622002Store depletion-activated CaT1 currents in rat basophilic leukemia mast cells are inhibited by 2-aminoethoxydiphenyl borate. Evidence for a regulatory component that controls activation of both CaT1 and CRAC (Ca(2+) release-activated Ca(2+) channel) channels.31
182456672008The role of TRPV6 in breast carcinogenesis.31
251729212014TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival.28


Yoshiro Suzuki ; Matthias A Hediger

TRPV6 (transient receptor potential cation channel, subfamily V, member 6)

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

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