TRPV5

Summary

TRPV5 (transient receptor potential cation channel subfamily V member 5, HGNC:3145) is a protein-coding gene on chromosome 7q34, encoding Transient receptor potential cation channel subfamily V member 5 (Q9NQA5). Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine.

This gene is a member of the transient receptor family and the TrpV subfamily. The calcium-selective channel 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.

Source: NCBI Gene 56302 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercalciuria, absorptive, 2 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 122 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_019841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3145
Approved symbol	TRPV5
Name	transient receptor potential cation channel subfamily V member 5
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	CaT2
Ensembl gene	ENSG00000127412
Ensembl biotype	protein_coding
OMIM	606679
Entrez	56302

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000265310, ENST00000439304, ENST00000442623

RefSeq mRNA: 1 — MANE Select: NM_019841 NM_019841

CCDS: CCDS5875

Canonical transcript exons

ENST00000265310 — 15 exons

Exon	Start	End
ENSE00000728612	142912482	142912750
ENSE00000728625	142915307	142915383
ENSE00000728630	142915482	142915568
ENSE00000728633	142925529	142925741
ENSE00000728649	142930058	142930180
ENSE00000728652	142930349	142930446
ENSE00001047561	142933332	142933746
ENSE00001090600	142908101	142908808
ENSE00001185100	142909490	142909596
ENSE00002433019	142928088	142928234
ENSE00002458587	142929428	142929565
ENSE00002467548	142914640	142914706
ENSE00002500822	142914881	142915046
ENSE00002517994	142929022	142929120
ENSE00002522739	142928691	142928866

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 64.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0495 / max 54.2742, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86648	0.0495	9

Top tissues by expression

115 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	64.86	gold quality
adult mammalian kidney	UBERON:0000082	63.46	gold quality
kidney	UBERON:0002113	58.09	gold quality
substantia nigra	UBERON:0002038	56.08	gold quality
blood	UBERON:0000178	55.91	gold quality
metanephros cortex	UBERON:0010533	54.47	gold quality
corpus callosum	UBERON:0002336	53.56	gold quality
Ammon’s horn	UBERON:0001954	52.29	gold quality
primary visual cortex	UBERON:0002436	50.61	gold quality
temporal lobe	UBERON:0001871	49.90	gold quality
amygdala	UBERON:0001876	49.72	gold quality
duodenum	UBERON:0002114	49.43	gold quality
sural nerve	UBERON:0015488	48.95	gold quality
cortex of kidney	UBERON:0001225	48.51	gold quality
prefrontal cortex	UBERON:0000451	48.00	gold quality
leukocyte	CL:0000738	47.38	silver quality
monocyte	CL:0000576	47.28	silver quality
putamen	UBERON:0001874	47.28	gold quality
hypothalamus	UBERON:0001898	46.93	gold quality
superior frontal gyrus	UBERON:0002661	45.12	silver quality
frontal cortex	UBERON:0001870	44.85	gold quality
cerebral cortex	UBERON:0000956	43.97	gold quality
ventricular zone	UBERON:0003053	43.44	gold quality
tonsil	UBERON:0002372	43.36	gold quality
granulocyte	CL:0000094	42.90	silver quality
bone marrow cell	CL:0002092	42.58	gold quality
skeletal muscle tissue	UBERON:0001134	42.43	gold quality
brain	UBERON:0000955	41.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	41.85	gold quality
caudate nucleus	UBERON:0001873	41.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SLC24A3

miRNA regulators (miRDB)

15 targeting TRPV5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-6862-3P	97.92	64.86	531
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-6853-5P	93.94	61.88	114
HSA-MIR-4765	93.11	66.17	737
HSA-MIR-662	90.64	62.72	148

Literature-anchored findings (GeneRIF, showing 40)

• Functional properties of the epithelial Ca2+ channel, ECaC. (PMID:11765215)
• does not play a primary role in autosomal dominant hypercalciuria (PMID:12198212)
• Our results indicate that the pattern of CaT1 and CaT2 expression correlates with the Ca2+ uptake potential along the differentiation of cultured human trophoblasts isolated from term placenta (PMID:12390878)
• The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption. (PMID:16291808)
• Immunohistochemistry of placental villi sections evidenced presence of TRPV5-TRPV6 channels in basal and apical syncytiotrophoblast plasma membranes. (PMID:16564089)
• WNK4 positively regulates TRPV5-mediated Ca transport & inhibitory effect of thiazide-sensitive Na+Cl- cotransporter on this process may be involved in pathogenesis of hypercalciuria of familial hyperkalemic hypertension caused by gene mutation in WNK4. (PMID:17018846)
• TRPV5 is involved in regulation and function in renal Ca2+ reabsorption and overall Ca2+ homeostasis–{review} (PMID:17217059)
• TRPV5 and TRPV6 are regulated by calbindin-D(28k), klotho and BSPRY (B-box and SPRY-domain-containing protein) at different levels throughout the epithelial cell [review] (PMID:17233615)
• malin ubiquitinates PTG in a laforin-dependent manner, both in vivo and in vitro, and targets PTG for proteasome-dependent degradation. These results suggest an additional mechanism, involving laforin and malin, in regulating glycogen metabolism (PMID:18077461)
• activation of protein kinase C increases cell surface abundance of TRPV5 by inhibiting endocytosis (PMID:18305097)
• review covers the distinctive properties and regulation of the highly Ca(2+)-selective TRPV5 channel and highlights the implications for our understanding of the process of Ca(2+) reabsorption. (PMID:18596722)
• This study was aimed at the mechanism underlying the difference in the effects of WNK4 on TRPV5 and TRPV6 through analyzing the difference in TRPV5 and TRPV6 expression in the plasma membrane. (PMID:18703016)
• Genotyping TRPV5 in renal hypercalciuria revealed three non-synonymous and five synonymous polymorphisms. Electrophysiological study of the TRPV5 mutants did not reveal significant functional changes compared to wild-type TRPV5 channel recordings. (PMID:19131347)
• The expression pattern and the selective Ca2+ permeation properties of TRPV5 channel indicate an important role of this channel in the Ca2+ homeostasis. (PMID:19140341)
• Activation of the CaR stimulates TRPV5-mediated Ca(2+) influx via a PMA-insensitive PKC isoform pathway. (PMID:19157541)
• the A563T variation in TRPV5 may contribute to the superior ability of renal Ca(2+) conservation in African Americans (PMID:19261737)
• human myeloid leukemia cells coexpress functional TRPV5 and TRPV6 calcium channels that may interact with each other and contribute into intracellular Ca(2+) signaling (PMID:19295174)
• Parathyroid hormone activates the cAMP-PKA signaling cascade, which rapidly phosphorylates threonine-709 of TRPV5, increasing the channel’s open probability and promoting Ca(2+) reabsorption in the distal nephron. (PMID:19423690)
• Data show that TRPV5 and TRPV6 expression is decreased in PE. (PMID:20178461)
• Retinal pigment epithelium expresses the epithelial calcium channels TRPV5 and TRPV6, the most calcium-selective channels of the TRP superfamily. (PMID:20405023)
• Findings suggest that TRPV-5 contributes to maintaining the homeostasis of the human skeleton via a negative feedback loop in RANKL-induced bone resorption. (PMID:20547482)
• A calmodulin binding site was located in the C-termini of TRPV2 (654-683) and TRPV5 (587-616). (PMID:20686800)
• TRPV5 channel is susceptible for helix breaking mutations and the proximal intracellular region of TM5 of this channel plays an important role in Ca(2+)-dependent inactivation (PMID:21035851)
• G(2)/M cell cycle arrest was preceded by activation of TRPV5/6-like nonselective cation channels in the plasma membrane resulting in an elevated Ca(2+) entry as evident from fura-2 Ca(2+) imaging. (PMID:21063097)
• WNK4 and NHERF2 synergistically regulate TRPV5 by enhancing its forward trafficking and increasing its stability at plasma membrane, respectively. (PMID:21187068)
• Data show that calmodulin negatively modulates TRPV5 activity, which is reversed by parathyroid hormone-mediated channel phosphorylation. (PMID:21576356)
• apically secreted tissue transglutaminase functions as an inhibitor of TRPV5 and thereby contributes to the regulation of body Ca2+ homeostasis. (PMID:21952826)
• The TRPV6 is a close homolog of TRPV5, yet their calmodulin binding sites display diversity in binding modes, binding stoichiometries and binding affinities which may fine-tune the response of the channels to varying Ca(2+)-concentrations. (PMID:22354706)
• urinary plasmin could contribute to the downstream effects of proteinuria on the tubulointerstitium by negatively modulating TRPV5 (PMID:23024298)
• TRPML3 and TRPV5 heteromers could have a biological function (PMID:23469151)
• These results suggest that TRPV5 and TRPV6 are crucial gates controlling cadmium and zinc levels in the human body. (PMID:23968883)
• Data indicate that transient receptor potential vanilloid type 5 (TRPV5) plasma membrane retention is regulated via lipid rafts. (PMID:23970553)
• these data showed that TRPV5/TRPV6 in human lymphocytes are functionally active, and their activity is associated with proliferative status of blood cells. (PMID:24592736)
• Decreased expression of TRPV5 is associated with non-small cell lung cancer. (PMID:24761864)
• Upregulating the expression of TRPV5 can be utilized to manipulate transmembrane Ca2+ transport, and may serve as an alternative for the treatment of Ca2+ balance-related diseases. (PMID:25139832)
• High TRPV5 expression is aassociated with adenoma of parathyroid glands. (PMID:25164318)
• Klotho up-regulates TRPV5 from both the inside and outside of cells. (PMID:25378396)
• Data found that a TRPV5 polymorphism (rs4236480) was observed to be associated with stone multiplicity of calcium nephrolithiasis, as the risk of stone multiplicity was higher in patients with the TT+CT genotype than in patients with the CC genotype (PMID:26089600)
• These findings indicate that the A563T variation induces structural, dynamical, and electrostatic changes in the TRPV5 pore, providing structural insight into the functional alterations associated with the A563T variation. (PMID:26837804)
• TRPV5 and TRPV6 lack a positively charged residue in the TM4-TM5 loop that was shown to interact with PI(4,5)P2 in TRPV1, which shows high affinity for this lipid (PMID:27291418)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trpv5	ENSMUSG00000036899
rattus_norvegicus	Trpv5	ENSRNOG00000015394
drosophila_melanogaster		FBGN0036414
drosophila_melanogaster	iav	FBGN0086693
caenorhabditis_elegans		WBGENE00003841
caenorhabditis_elegans		WBGENE00003889

Paralogs (5): TRPV4 (ENSG00000111199), TRPV6 (ENSG00000165125), TRPV3 (ENSG00000167723), TRPV2 (ENSG00000187688), TRPV1 (ENSG00000196689)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily V member 5 — Q9NQA5 (reviewed: Q9NQA5)

Alternative names: Calcium transport protein 2, Epithelial calcium channel 1, Osm-9-like TRP channel 3

All UniProt accessions (2): Q9NQA5, H7C2J6

UniProt curated annotations — full annotation on UniProt →

Function. Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine. Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules. The channel is activated by low internal calcium level and the current exhibits an inward rectification. A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay. Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating.

Subunit / interactions. Homotetramer and probably heterotetramer with TRPV6. Interacts with TRPV6. Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane. Interacts with calmodulin. Interacts with BSPRY, which results in its inactivation.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed at high levels in kidney, small intestine and pancreas, and at lower levels in testis, prostate, placenta, brain, colon and rectum.

Post-translational modifications. Glycosylated.

Activity regulation. Activated by WNK3.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV5 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQA5-1	1	yes
Q9NQA5-2	2

RefSeq proteins (1): NP_062815* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR005821	Ion_trans_dom	Domain
IPR008344	TRPV5/TRPV6	Family
IPR008346	TRPV5	Family
IPR024862	TRPV	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF00520, PF12796

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (38 total): topological domain 6, transmembrane region 6, repeat 6, region of interest 4, sequence variant 4, modified residue 2, splice variant 2, chain 1, intramembrane region 1, compositionally biased region 1, binding site 1, glycosylation site 1, mutagenesis site 1, helix 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5OEO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQA5-F1	82.87	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 542

Post-translational modifications (2): 685, 689

Glycosylation sites (1): 358

Mutagenesis-validated functional residues (1):

Position	Phenotype
358	loss of glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 73 (showing top): GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CALCIUM_ION_IMPORT, GOBP_REGULATION_OF_URINE_VOLUME, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_IMPORT_INTO_CELL, GOBP_PROTEIN_TETRAMERIZATION, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_RENAL_SYSTEM_PROCESS, GOCC_APICAL_PART_OF_CELL, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (11): calcium ion transport (GO:0006816), regulation of urine volume (GO:0035809), protein homotetramerization (GO:0051289), calcium ion homeostasis (GO:0055074), calcium ion transport into cytosol (GO:0060402), calcium ion transmembrane transport (GO:0070588), calcium ion import across plasma membrane (GO:0098703), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), calcium ion transmembrane import into cytosol (GO:0097553)

GO Molecular Function (5): calcium channel activity (GO:0005262), calmodulin binding (GO:0005516), metal ion binding (GO:0046872), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), calcium channel complex (GO:0034704), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Stimuli-sensing channels	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transmembrane import into cytosol	2
transport	2
metal ion transport	1
renal system process	1
regulation of body fluid levels	1
protein homooligomerization	1
protein tetramerization	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
positive regulation of cytosolic calcium ion concentration	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
calcium ion import	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
calcium ion transmembrane transport	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
protein binding	1
cation binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
cation channel complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1020 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPV5	MCOLN3	Q8TDD5	915
TRPV5	KL	Q9UEF7	896
TRPV5	S100A10	P08206	883
TRPV5	NIPSNAP1	Q9BPW8	835
TRPV5	FGF23	Q9GZV9	816
TRPV5	PTH	P01270	795
TRPV5	TRPM6	Q9BX84	786
TRPV5	GUSB	P08236	741
TRPV5	LCTL	Q6UWM7	739
TRPV5	S100G	P29377	731
TRPV5	TRPM4	Q8TD43	722
TRPV5	TRPM7	Q96QT4	720
TRPV5	SLC12A1	Q13621	715
TRPV5	TRPV6	Q9H1D0	712
TRPV5	CALB1	P05937	701

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TRPV5	ATF1	psi-mi:“MI:0914”(association)	0.530
CALB1	TRPV5	psi-mi:“MI:0403”(colocalization)	0.460
CALB1	TRPV5	psi-mi:“MI:0915”(physical association)	0.460
TRPV5	CALB1	psi-mi:“MI:0915”(physical association)	0.460
EWSR1	TRPV5	psi-mi:“MI:0915”(physical association)	0.370
TRPV5	CREB1	psi-mi:“MI:0914”(association)	0.350
TRPV5	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
USF2	TRPV5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): USP15 (Affinity Capture-MS), PUS1 (Affinity Capture-MS), PSPC1 (Affinity Capture-MS), STAT3 (Affinity Capture-MS), RPIA (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), ATF1 (Affinity Capture-MS), CREB1 (Affinity Capture-MS), TRMT61B (Affinity Capture-MS), UHRF1 (Affinity Capture-MS), GCLM (Affinity Capture-MS), HMGN1 (Affinity Capture-MS), YY1 (Affinity Capture-MS), NUP35 (Affinity Capture-MS), RNF138 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PXA5, O18784, O35119, O35433, O62852, P0C550, P19334, P34586, P34641, P48994, P48995, P69744, P79100, P97414, Q0JKV1, Q12324, Q5ICL9, Q61056, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q875M2, Q8GXE6, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q96L42, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9MYV9, Q9NQA5, Q9P2G1, Q9QUQ5, Q9QX01, Q9QX29

Diamond homologs: A0A1D5PXA5, O35433, P69744, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9NQA5, Q9R186, Q9WTR1, Q9WUD2, Q9XSM3, Q9Y5S1, Q810B6, Q9P2R3, A0A0K0PU92, O00221, O54910, P25799, P25963, P83757, P98150, Q00653, Q03017, Q08353, Q25338, Q2QXZ2, Q2RAQ5, Q3UMT1, Q495B1, Q5EFR1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKCA	“up-regulates activity”	TRPV5	phosphorylation
UBR4	“down-regulates quantity by destabilization”	TRPV5	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

122 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	102
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2500119	NM_019841.7(TRPV5):c.1792G>A (p.Val598Met)	Pathogenic

SpliceAI

2257 predictions. Top by Δscore:

Variant	Effect	Δscore
7:142908804:CAACC:C	acceptor_gain	1.0000
7:142908807:CC:C	acceptor_gain	1.0000
7:142908808:CC:C	acceptor_gain	1.0000
7:142912477:CTCA:C	donor_loss	1.0000
7:142912478:TCA:T	donor_loss	1.0000
7:142912479:CA:C	donor_loss	1.0000
7:142912481:C:CA	donor_loss	1.0000
7:142914634:CCTTA:C	donor_loss	1.0000
7:142914635:CTTA:C	donor_loss	1.0000
7:142914636:TTAC:T	donor_loss	1.0000
7:142914637:TA:T	donor_loss	1.0000
7:142914638:A:AC	donor_gain	1.0000
7:142914638:ACCGG:A	donor_loss	1.0000
7:142914639:C:CC	donor_gain	1.0000
7:142914717:C:CT	acceptor_gain	1.0000
7:142914876:CTGA:C	donor_loss	1.0000
7:142914877:TGAC:T	donor_loss	1.0000
7:142914878:GAC:G	donor_loss	1.0000
7:142914880:CCTT:C	donor_gain	1.0000
7:142915042:TGATG:T	acceptor_gain	1.0000
7:142915043:GATG:G	acceptor_gain	1.0000
7:142915044:ATG:A	acceptor_gain	1.0000
7:142915045:TG:T	acceptor_gain	1.0000
7:142915045:TGCT:T	acceptor_loss	1.0000
7:142915046:GCTG:G	acceptor_loss	1.0000
7:142915047:C:CA	acceptor_loss	1.0000
7:142915047:C:CC	acceptor_gain	1.0000
7:142915048:T:G	acceptor_loss	1.0000
7:142915056:C:CT	acceptor_gain	1.0000
7:142915057:A:T	acceptor_gain	1.0000

AlphaMissense

4775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:142914949:A:G	W462R	0.997
7:142914949:A:T	W462R	0.997
7:142914680:G:C	F493L	0.996
7:142914680:G:T	F493L	0.996
7:142914682:A:G	F493L	0.996
7:142914647:A:C	F504L	0.995
7:142914647:A:T	F504L	0.995
7:142914649:A:G	F504L	0.995
7:142925691:C:A	K320N	0.992
7:142925691:C:G	K320N	0.992
7:142912564:A:T	L569H	0.991
7:142925688:C:A	W321C	0.991
7:142925688:C:G	W321C	0.991
7:142925690:A:G	W321R	0.991
7:142925690:A:T	W321R	0.991
7:142912554:G:C	N572K	0.989
7:142912554:G:T	N572K	0.989
7:142912564:A:G	L569P	0.989
7:142914652:C:G	G503R	0.989
7:142914652:C:T	G503R	0.989
7:142914907:C:G	G476R	0.988
7:142925704:A:G	L316P	0.988
7:142912584:G:C	F562L	0.987
7:142912584:G:T	F562L	0.987
7:142912586:A:G	F562L	0.987
7:142912564:A:C	L569R	0.986
7:142914906:C:T	G476D	0.986
7:142914929:G:C	F468L	0.986
7:142914929:G:T	F468L	0.986
7:142914931:A:G	F468L	0.986

dbSNP variants (sampled 300 via entrez): RS1000223360 (7:142920827 C>A), RS1000229757 (7:142933646 G>A,C,T), RS1000254193 (7:142933830 C>T), RS1000309592 (7:142915235 C>G), RS1000343904 (7:142921558 G>A), RS1000506658 (7:142919822 C>G,T), RS1000534316 (7:142934901 T>C), RS1000574005 (7:142921045 A>G), RS1000677986 (7:142923126 A>G), RS1000996334 (7:142925392 A>G), RS1001103756 (7:142931205 G>A), RS1001245233 (7:142917347 G>A,T), RS1001416681 (7:142933906 G>A), RS1001466109 (7:142921857 C>T), RS1001471830 (7:142934074 T>G)

Disease associations

OMIM: gene MIM:606679 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hypercalciuria, absorptive, 2	Limited	Autosomal recessive
urinary system disorder	Limited	Autosomal recessive

Mondo (2): hypercalciuria, absorptive, 2 (MONDO:0007748), urinary system disorder (MONDO:0002118)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004860_10	Alcoholic chronic pancreatitis	3.000000e-06
GCST004860_42	Alcoholic chronic pancreatitis	2.000000e-06
GCST005275_22	Cancer	3.000000e-07
GCST010397_112	Gut microbiota (bacterial taxa, rank normal transformation method)	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D014570	Urologic Diseases	C12.050.351.968; C12.200.777; C12.950
C562790	Hypercalciuria, Absorptive, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1628474 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,884 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
ruthenium red	Channel blocker	6.9	pIC50
gentamicin	Inhibition	6.0	pIC50
tetrahydrocannabivarin	Inhibition	5.4	pIC50
oxoglaucine	Inhibition	4.82	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.25	IC50	560	nM	CHEMBL4777551
5.32	IC50	4800	nM	TETRAHYDROCANNABIVARIN

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[[4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]cyclohexyl]piperazin-1-yl]methyl]-1H-pyridin-2-one	1685541: Inhibition of human TRPV5 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.5600	uM
(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol	1845597: Inhibition of TRPV5 channel (unknown origin) by Patch-clamp assay	ic50	4.8000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases import	1
Calcium	affects cotreatment, decreases reaction, increases uptake	1
Cholecalciferol	affects cotreatment, increases expression	1
Copper	affects cotreatment, decreases expression	1
Cuprizone	increases expression, affects cotreatment	1
Haloperidol	affects cotreatment, increases expression	1
Lead	affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Zinc	increases import	1
Aflatoxin B1	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4411008	Binding	Inhibition of TRPV5 channel (unknown origin)	Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model. — ACS Med Chem Lett
CHEMBL4680551	ADMET	Inhibition of human TRPV5 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor — RSC Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XU75	HAP1 TRPV5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

153 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02805504	PHASE4	COMPLETED	Liposomal Bupivacaine for Postoperative Pain Control in Urologic Procedures
NCT03591289	PHASE4	WITHDRAWN	Does Depth of Neuromuscular Blockade (NMB) Affect Surgical Conditions in Obese Patients Undergoing Robotic Surgery
NCT05082142	PHASE4	COMPLETED	Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser Enucleation of the Prostate (HoLEP)
NCT00239265	PHASE3	COMPLETED	Tamsulosin Phase III Clinical Trial -Double-Blind, Placebo Controlled Study in Female Patients With Lower Urinary Tract Syndrome
NCT00239317	PHASE3	COMPLETED	Tamsulosin Phase III Clinical Trial -Double-Blind, Placebo Controlled Study in Male Patients With Lower Urinary Tract Syndrome
NCT00258089	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Oral Levofloxacin Compared With Oral Ciprofloxacin in the Treatment of Complicated Urinary Tract Infections
NCT00258102	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Levofloxacin Compared With Lomefloxacin in the Treatment of Complicated Urinary Tract Infections
NCT00384891	PHASE3	TERMINATED	Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer
NCT01530620	PHASE3	COMPLETED	Efficacy and Tolerability of Propiverine Hydrochloride in Patients With Neurogenic Detrusor Overactivity
NCT01638000	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mirabegron Compared to Solifenacin in Patients With Overactive Bladder Who Were Previously Treated With Another Medicine But Were Not Satisfied With That Treatment.
NCT01908829	PHASE3	COMPLETED	A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin)
NCT02254915	PHASE3	WITHDRAWN	SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists’ Research Operation Preserving Evolution Study I
NCT03927781	PHASE3	COMPLETED	Perioperative Pregabalin in Ureteroscopy: a Pilot
NCT04042402	PHASE3	ACTIVE_NOT_RECRUITING	Long Term Extension Study in Patients With Primary Hyperoxaluria
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT06858319	PHASE3	RECRUITING	Open-label Extension Study of Zigakibart in Adults With IgA Nephropathy.
NCT01060254	PHASE2	TERMINATED	A Study to Evaluate the Pain Relieving Effects, Safety, and Tolerability of JNJ-42160443 for the Relief of Bladder Pain
NCT01340027	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety and Tolerability of Mirabegron and Solifenacin Succinate Alone and in Combination for the Treatment of Overactive Bladder
NCT01613586	PHASE2	COMPLETED	A Randomized Study Comparing Placebo and ASP3652 in the Treatment of Women With Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC)
NCT02307487	PHASE2	COMPLETED	Safety of Pre-TURBT Intravesical Instillation of Escalating Doses of TC-3 Gel and MMC in NMIBC Patients
NCT03847909	PHASE2	COMPLETED	A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2
NCT04387448	PHASE2	TERMINATED	A Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease
NCT05935748	PHASE2	TERMINATED	Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc)
NCT06164600	PHASE2	COMPLETED	Bovine Colostrum for Prophylaxis Against Recurrent Urinary Tract Infection in Children
NCT01231997	PHASE1	COMPLETED	Clinical Study to Investigate the Safety and Pharmacokinetics of Udenafil Tablet in Renal Impaired Male Patients
NCT01232010	PHASE1	COMPLETED	Clinical Study to Investigate the Safety and Pharmacokinetics of SK3530 Tablet in Renal Impaired Male Patients
NCT02052713	PHASE1	COMPLETED	Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin Hydrochloride (HCL) Combination Capsule in Fasted State
NCT02058576	PHASE1	COMPLETED	Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in Fed State
NCT02386111	PHASE1	TERMINATED	A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma
NCT02543645	PHASE1	TERMINATED	A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer
NCT03258658	PHASE1	RECRUITING	Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures
NCT03463239	PHASE1	NOT_YET_RECRUITING	Bioengineered Penile Tissue Constructs for Irreversibly Damaged Penile Corpora
NCT03899298	PHASE1	NOT_YET_RECRUITING	Safety and Clinical Outcomes With Amniotic and Umbilical Cord Tissue Therapy for Numerous Medical Conditions
NCT04731376	PHASE1	ACTIVE_NOT_RECRUITING	Perioperative Testosterone Replacement Therapy for the Improvement of Post-Operative Outcomes in Patients With Low Testosterone
NCT04972890	PHASE2/PHASE3	UNKNOWN	The Outcomes of Intracavernosal Umbilical Cord Mesenchymal Stem Cells Implantation in Patients With Diabetic Erectile Dysfunction
NCT05878951	PHASE2/PHASE3	RECRUITING	Examining the Effects of Intra-detrusor Botox at Time of HoLEP in Men With Overactive Bladder Symptoms
NCT02291432	PHASE1/PHASE2	COMPLETED	Autologous Cell Therapy for Stress Urinary Incontinence in Males Following Prostate Surgery
NCT02401542	PHASE1/PHASE2	TERMINATED	Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
NCT03081858	PHASE1/PHASE2	COMPLETED	Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer