Details for: TRPV5

Gene ID: 56302

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TRPV5

Ensembl ID: ENSG00000127412

Description: transient receptor potential cation channel subfamily V member 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • kidney connecting tubule epithelial cell CL1000768
    CSI 6.93
    rCSI 17.57%
    PRS 99.84
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.7
    rCSI 18.02%
    PRS 99.85

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Size: Proportional to Target Cell CSI magnitude
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Transient receptor potential cation channel subfamily V member 5 ([TRPV5](/details-gene/56302)) is a protein-coding gene located on chromosome 7q34. It functions as a highly selective calcium channel essential for calcium ion homeostasis. Its expression is exceptionally specific, serving as a defining marker for epithelial cells in the distal nephron of the kidney. **Overall**, it is most significant in the '[kidney connecting tubule epithelial cell](/details-cell/CL1000768)' and '[kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849)', where it plays a critical gatekeeping role in the final step of active calcium reabsorption from urine. ## Cellular Roles and Expression Landscape The expression profile of [TRPV5](/details-gene/56302) indicates a highly specialized function within the renal system. Its significance is overwhelmingly concentrated in two closely related cell types: the '[kidney connecting tubule epithelial cell](/details-cell/CL1000768)' (CSI: 6.93) and the '[kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849)' (CSI: 1.70). This restricted expression pattern, first detailed in early cloning studies ([Link](https://doi.org/10.1006/geno.2000.6203)), establishes [TRPV5](/details-gene/56302) as a key component of the machinery responsible for fine-tuning the body's calcium levels. Its localization to the '[apical plasma membrane](/details-link/GO:0016324)' of these cells positions it to mediate the rate-limiting step of calcium entry from the tubular fluid back into the body. The lack of significant expression in other tissues suggests a dedicated role in renal physiology, distinct from other members of the TRP channel family. ## Pathways and Molecular Function Functionally, [TRPV5](/details-gene/56302) is annotated with '[calcium channel activity](/details-link/GO:0005262)' and is a central participant in '[calcium ion import across plasma membrane](/details-link/GO:0098703)' and broader '[calcium ion homeostasis](/details-link/GO:0055074)'. As a member of the transient receptor potential (TRP) channel family, its function is categorized within Reactome pathways such as '[Trp channels](/details-link/R-HSA-3295583)' and '[ion channel transport](/details-link/R-HSA-983712)'. The channel is known to assemble into functional homotetramers ([Protein homotetramerization](/details-link/GO:0051289)). Its activity is subject to complex regulation, evidenced by its capacity for '[calmodulin binding](/details-link/GO:0005516)', which provides a mechanism for feedback inhibition in response to high intracellular calcium. Furthermore, its function can be modulated by signaling kinases, such as WNK3, which positively regulates its activity ([Link](https://doi.org/10.1152/ajprenal.90229.2008)). ## Research Directions Given its critical and specific role in calcium balance, [TRPV5](/details-gene/56302) is a gene of significant clinical and physiological interest. ### Proposed Hypotheses 1. **Genetic variants in [TRPV5](/details-gene/56302) contribute to the risk of nephrolithiasis (kidney stones) and idiopathic hypercalciuria.** Dysfunctional or misregulated channels could lead to excessive calcium in the urine, promoting stone formation. A population-based genetic association study could test this by sequencing the [TRPV5](/details-gene/56302) locus in patients with these conditions compared to healthy controls. 2. **Hormonal regulation of whole-body calcium, particularly via parathyroid hormone (PTH) and active Vitamin D (1,25(OH)2D3), is mediated by post-translational modification and subsequent trafficking of [TRPV5](/details-gene/56302) to the apical membrane.** This hypothesis posits that these hormones do not simply alter gene expression but also acutely control the number of active channels at the cell surface. ### Key Experiment To test the second hypothesis regarding hormonal regulation, an ideal experiment would involve using a polarized culture of '[kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849)s'. These cells would be treated with PTH or 1,25(OH)2D3 over a time course. Changes in [TRPV5](/details-gene/56302) localization would be quantified using cell surface biotinylation assays followed by immunoblotting, which specifically labels and isolates plasma membrane proteins. Complementarily, super-resolution microscopy could be used to visualize the trafficking of fluorescently-tagged [TRPV5](/details-gene/56302) to the apical membrane in real-time following hormone stimulation. ### Therapeutic Potential The high tissue specificity and crucial function of [TRPV5](/details-gene/56302) make it an attractive therapeutic target. * **Inhibition:** For conditions of hypercalcemia or hypercalciuria-associated kidney stones, a small molecule inhibitor of [TRPV5](/details-gene/56302) could be highly effective. Such a drug would act as a targeted diuretic, specifically promoting calcium excretion with potentially fewer side effects than current broad-spectrum diuretics. * **Activation:** Conversely, a specific [TRPV5](/details-gene/56302) agonist could be developed to treat hypocalcemia or to enhance calcium retention in patients with osteoporosis. By increasing renal calcium reabsorption, such a therapeutic could help maintain bone mineral density. The development of specific modulators remains a key challenge and a promising area of drug discovery.

Genular Protein ID: 2210999495

Symbol: TRPV5_HUMAN

Name: Transient receptor potential cation channel subfamily V member 5

UniProtKB Accession Codes:

Q9NQA5 A0A0A6YY98 A4D2H7 E9PBZ6 Q8N4C1 Q8NDW5 Q8NDX7 Q8NDX8 Q96PM6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 2 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 DrugBank 3 DrugCentral 1 EMBL 8 Ensembl 4 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 3 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 1 Rhea 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10945469

Title: Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial calcium channel (ECAC1).

PubMed ID: 10945469

DOI: 10.1006/geno.2000.6203

PubMed ID: 11549322

Title: Structural conservation of the genes encoding CaT1, CaT2, and related cation channels.

PubMed ID: 11549322

DOI: 10.1006/geno.2001.6606

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18768590

Title: WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway.

PubMed ID: 18768590

DOI: 10.1152/ajprenal.90229.2008

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

Sequence Information:

  • Length: 729
  • Mass: 82562
  • Checksum: DAF91FF9E9ECE118
  • Sequence:
    • MGGFLPKAEG PGSQLQKLLP SFLVREQDWD QHLDKLHMLQ QKRILESPLL RASKENDLSV 
LRQLLLDCTC DVRQRGALGE TALHIAALYD NLEAALVLME AAPELVFEPT TCEAFAGQTA 
LHIAVVNQNV NLVRALLTRR ASVSARATGT AFRHSPRNLI YFGEHPLSFA ACVNSEEIVR 
LLIEHGADIR AQDSLGNTVL HILILQPNKT FACQMYNLLL SYDGHGDHLQ PLDLVPNHQG 
LTPFKLAGVE GNTVMFQHLM QKRRHIQWTY GPLTSILYDL TEIDSWGEEL SFLELVVSSD 
KREARQILEQ TPVKELVSFK WNKYGRPYFC ILAALYLLYM ICFTTCCVYR PLKFRGGNRT 
HSRDITILQQ KLLQEAYETR EDIIRLVGEL VSIVGAVIIL LLEIPDIFRV GASRYFGKTI 
LGGPFHVIII TYASLVLVTM VMRLTNTNGE VVPMSFALVL GWCSVMYFTR GFQMLGPFTI 
MIQKMIFGDL MRFCWLMAVV ILGFASAFYI IFQTEDPTSL GQFYDYPMAL FTTFELFLTV 
IDAPANYDVD LPFMFSIVNF AFTIIATLLM LNLFIAMMGD THWRVAQERD ELWRAQVVAT 
TVMLERKLPR CLWPRSGICG CEFGLGDRWF LRVENHNDQN PLRVLRYVEV FKNSDKEDDQ 
EHPSEKQPSG AESGTLARAS LALPTSSLSR TASQSSSHRG WEILRQNTLG HLNLGLNLSE 
GDGEEVYHF