TRPV6

Summary

TRPV6 (transient receptor potential cation channel subfamily V member 6, HGNC:14006) is a protein-coding gene on chromosome 7q34, encoding Transient receptor potential cation channel subfamily V member 6 (Q9H1D0). Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine.

This gene encodes a member of a family of multipass membrane proteins that functions as calcium channels. The encoded protein contains N-terminal ankyrin repeats, which are required for channel assembly and regulation. Translation initiation for this protein occurs at a non-AUG start codon that is decoded as methionine. This gene is situated next to a closely related gene for transient receptor potential cation channel subfamily V member 5 (TRPV5). This locus has experienced positive selection in non-African populations, resulting in several non-synonymous codon differences among individuals of different genetic backgrounds.

Source: NCBI Gene 55503 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intestinal hypomagnesemia 1 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 403 total — 12 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 61
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14006
Approved symbol	TRPV6
Name	transient receptor potential cation channel subfamily V member 6
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	CaT1
Ensembl gene	ENSG00000165125
Ensembl biotype	protein_coding
OMIM	606680
Entrez	55503

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 retained_intron, 3 protein_coding

ENST00000359396, ENST00000431833, ENST00000436401, ENST00000474388, ENST00000485138, ENST00000489123, ENST00000615386, ENST00000619250

RefSeq mRNA: 1 — MANE Select: NM_018646 NM_018646

CCDS: CCDS5874

Canonical transcript exons

ENST00000359396 — 15 exons

Exon	Start	End
ENSE00001090568	142877651	142877773
ENSE00001090578	142877929	142878026
ENSE00001421087	142885389	142885745
ENSE00001922815	142871208	142871989
ENSE00002519793	142877142	142877279
ENSE00003492833	142876408	142876583
ENSE00003560939	142875078	142875164
ENSE00003578278	142873448	142873716
ENSE00003585242	142876739	142876837
ENSE00003597667	142875468	142875680
ENSE00003607805	142874904	142874980
ENSE00003627074	142874076	142874142
ENSE00003636682	142872372	142872478
ENSE00003641364	142875758	142875904
ENSE00003645577	142874491	142874656

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 96.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2758 / max 89.4423, expressed in 66 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86644	0.2017	55
86643	0.0413	5
86646	0.0170	8
86645	0.0159	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	96.94	gold quality
pancreas	UBERON:0001264	93.50	gold quality
duodenum	UBERON:0002114	88.79	gold quality
placenta	UBERON:0001987	88.32	gold quality
prostate gland	UBERON:0002367	88.05	gold quality
islet of Langerhans	UBERON:0000006	87.73	gold quality
gall bladder	UBERON:0002110	86.03	gold quality
lower esophagus mucosa	UBERON:0035834	83.25	gold quality
skin of abdomen	UBERON:0001416	83.23	gold quality
metanephros cortex	UBERON:0010533	82.48	gold quality
primary visual cortex	UBERON:0002436	81.98	gold quality
zone of skin	UBERON:0000014	81.77	gold quality
saliva-secreting gland	UBERON:0001044	81.24	gold quality
skin of leg	UBERON:0001511	80.79	gold quality
right frontal lobe	UBERON:0002810	79.72	gold quality
minor salivary gland	UBERON:0001830	79.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.41	gold quality
frontal cortex	UBERON:0001870	79.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.21	gold quality
prefrontal cortex	UBERON:0000451	79.03	gold quality
superior frontal gyrus	UBERON:0002661	78.34	gold quality
putamen	UBERON:0001874	77.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.88	gold quality
anterior cingulate cortex	UBERON:0009835	77.14	gold quality
cerebral cortex	UBERON:0000956	76.48	gold quality
adult mammalian kidney	UBERON:0000082	76.11	gold quality
caudate nucleus	UBERON:0001873	75.51	gold quality
tonsil	UBERON:0002372	74.86	gold quality
body of stomach	UBERON:0001161	74.54	gold quality
esophagus mucosa	UBERON:0002469	74.28	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	26.10
E-GEOD-81547	yes	24.55
E-ANND-3	yes	8.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, AR, ATF4, DDIT3, ESR1, SLC24A3, VDR

Literature-anchored findings (GeneRIF, showing 40)

• Gene expressed in human duodenum, placenta and pancreas homologous with calcium transporters/channels in other species. Function proposed to be calcium entry channel at apical membrane. (PMID:11208552)
• 1,25-Dihydroxyvitamin D3 increases mRNA expression of the CaT1 calcium channel in the Caco-2 intestinal cell line. (PMID:11545681)
• to characterize ECaC2 in more detail and to compare ites properties with those of Ecac1 to obtain a better understanding of transcellular Ca2+ transport in epithelia (PMID:11744752)
• regulatory component that controls activation of both CaT1 and CRAC (Ca(2+) release-activated Ca(2+) channel) channels. (PMID:12011062)
• role of TRPV6 as calcium sensor in rat and human cells (PMID:12138163)
• CaT1 is the channel protein that contributes to T-lymphocyte stores-operated Ca(2+) channels either alone or as a subunit in a heterogeneous channel complex. (PMID:12361955)
• 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 role of CaT1 in generating endogenous store-operated Ca(2+) current (I(SOC)) in the lymph node carcinoma of the prostate (LNCaP) human prostate cancer epithelial cell line (PMID:12584203)
• The effects of intracellular Mg(2+) on TRPV6 are partially reminiscent of the gating mechanism of inwardly rectifying K(+) channels and may represent a novel regulatory mechanism for TRPV6 function in vivo. (PMID:12601087)
• native channels responsible for ISOC are different from those for recombinant ITRPV6 and do not appear to be affected if one of their assumed subunits, TRPV6, is up- or down-regulated, suggesting a rather rigid subunit composition in vivo. (PMID:14534305)
• These results suggest that all components, i.e. the store-operated calcium channel (SOCC), endoplasmic reticulum, and mitochondria, somehow contribute to the altered Ca2+ signalling in bipolar disorder. (PMID:14604453)
• TRPV6 is a Ca2+-selective TRP channel lined by amino acid side chains rather than main chain carbonyls (PMID:14736889)
• it is unlikely that CaT1 is a component of native CRAC channels in mast cells (PMID:15020691)
• the TRPV6 channel is regulated by calcium (PMID:15184369)
• the third ANK repeat of TRPV6 is required for functional subunit assembly (PMID:15192090)
• the voltage dependence of TRPV6-mediated Ca(2+) influx is of physiological importance since it occurs at cytosolic Ca(2+) buffering and takes place within a physiologically relevant membrane potential range (PMID:15582993)
• a strong functional link between the operation of expressed TRPC channels and endogenous SOC activity. (PMID:15647288)
• PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated calcium influx in HEK293 cells (PMID:15894168)
• Human CAT1 is involved in erythroid hematopoiesis through its role in importing L-arginine, which appears to be essential for the differentiation of red blood cells. (PMID:16210335)
• expression of TRPV6 increases the rate of Ca(2+) dependent cell proliferation which is a prerequisite for its potential role in tumor progression (PMID:16356545)
• therefore suggesting that TRPC1 and/or TRPC3 proteins are responsible for the response to alpha-adrenergic stimulation but that TRPC1, TPRC3 and TRPV6 proteins, expressed alone or concomitantly, are not sufficient for SOC formation. (PMID:16529812)
• Immunohistochemistry of placental villi sections evidenced presence of TRPV5-TRPV6 channels in basal and apical syncytiotrophoblast plasma membranes. (PMID:16564089)
• The 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 (PMID:16574738)
• Data suggest that the rate of TRPV6 protein evolution is significantly accelerated in the human lineage and that the TRPV6 haplotype defined by the derived alleles at C157R, M378V and M681T conferred a selective advantage. (PMID:16717058)
• duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced (PMID:17002582)
• We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells. (PMID:17197020)
• there is growing evidence that transcriptional regulation of TRPV6 in certain tissues undergoing malignant transformation, such as prostate cancer, is linked to cancer progression–{REVIEW} (PMID:17217060)
• 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)
• the TRPV6 channel is a key element in Ca(2+)/1,25-dihydroxyvitamin D3-induced differentiation of human keratinocytes (PMID:17550901)
• a cheese whey protein digest increased the calcium uptake by the CHO-hCaT1 cells, human intestinal Caco-2 cells, and in vivo using rats with enteral feeding (PMID:17587679)
• TRPV6 may be a novel target for the development of calcium channel inhibitors to treat breast adenocarcinoma expressing TRPV6. (PMID:18245667)
• The ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria. (PMID:18276610)
• all non-African populations carry a signature of selection on the same haplotype at the TRPV6 locus, demonstrating a widespread parallel selection event acting on standing genetic variation in humans (PMID:18301763)
• this study presents the first physiological function of Nipsnap1 as an associated protein inhibiting transient receptor potential vanilloid channel 6 activity that possibly exerts its effect directly at the plasma membrane (PMID:18392847)
• Results suggest that TRPV6 channels in T84 cells contribute to the calcium entry/signalling pathway that is sensitive to 17beta-estradiol. (PMID:18395250)
• CypB is a new TRPV6 accessory protein with potential involvement in TRPV6 channel activation through its peptidyl-prolyl cis/trans isomerase activity (PMID:18445599)
• Regulation of TRPV6 gene expression by short chain fatty acids may be a molecular mechanism involved in the promotion of calcium absorption by fructooligosaccharides in rats. (PMID:19056662)
• The expression pattern and the selective Ca2+ permeation properties of TRPV6 channel indicate an important role of this channel in the Ca2+ homeostasis and probably in malignant transformation of blood cells. (PMID:19140341)
• These results further support the idea that the skewed polymorphism of TRPV6 is generated by recent positive selection rather than being the result of demographic events in the Guangzhou population. (PMID:19169858)
• 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)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpv6	ENSDARG00000014496
mus_musculus	Trpv6	ENSMUSG00000029868
rattus_norvegicus	Trpv6	ENSRNOG00000014714
drosophila_melanogaster		FBGN0036414
drosophila_melanogaster	iav	FBGN0086693
caenorhabditis_elegans		WBGENE00003841
caenorhabditis_elegans		WBGENE00003889

Paralogs (5): TRPV4 (ENSG00000111199), TRPV5 (ENSG00000127412), TRPV3 (ENSG00000167723), TRPV2 (ENSG00000187688), TRPV1 (ENSG00000196689)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily V member 6 — Q9H1D0 (reviewed: Q9H1D0)

Alternative names: CaT-like, Calcium transport protein 1, Epithelial calcium channel 2

All UniProt accessions (4): A0A1X7SBT1, C9J9W0, C9JHY1, Q9H1D0

UniProt curated annotations — full annotation on UniProt →

Function. Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine. Important for normal Ca(2+) ion homeostasis in the body, including bone and skin. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating.

Subunit / interactions. Homotetramer. Probably also forms heterotetramers with TRPV5. Interacts with TRPV5. 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 BSPRY. Interacts with TCAF1 and TCAF2 isoform 2. Interacts with calmodulin.

Subcellular location. Cell membrane.

Tissue specificity. Expressed at high levels in the gastrointestinal tract, including esophagus, stomach, duodenum, jejunum, ileum and colon, and in pancreas, placenta, prostate and salivary gland. Expressed at moderate levels in liver, kidney and testis. Expressed in trophoblasts of placenta villus trees (at protein level). Expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but not detected in healthy prostate tissue and benign prostatic hyperplasia.

Post-translational modifications. Glycosylated. Phosphorylation at Tyr-201 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at this site by PTPN1. Phosphorylation by PRKCA at the calmodulin binding site delays channel inactivation.

Disease relevance. Hyperparathyroidism, transient neonatal (HRPTTN) [MIM:618188] An autosomal recessive disease characterized by impaired transplacental maternal-fetal transport of calcium, high serum PTH levels and signs of metabolic bone disease in the neonatal period. Skeletal anomalies include generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. Affected individuals experience postnatal respiratory and feeding difficulties. The condition improves within a short time after birth once calcium is provided orally. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H1D0-1	1	yes
Q9H1D0-2	2

RefSeq proteins (1): NP_061116* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR005821	Ion_trans_dom	Domain
IPR008344	TRPV5/TRPV6	Family
IPR008345	TrpV6	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 (115 total): helix 34, strand 19, turn 13, sequence variant 11, topological domain 8, transmembrane region 6, repeat 6, mutagenesis site 5, region of interest 3, modified residue 2, sequence conflict 2, chain 1, intramembrane region 1, short sequence motif 1, binding site 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
7S8B	ELECTRON MICROSCOPY	2.43
7S89	ELECTRON MICROSCOPY	2.54
8FOA	ELECTRON MICROSCOPY	2.66
7S88	ELECTRON MICROSCOPY	2.69
8FOB	ELECTRON MICROSCOPY	2.71
9CUJ	ELECTRON MICROSCOPY	2.78
8SP8	ELECTRON MICROSCOPY	2.79
7S8C	ELECTRON MICROSCOPY	2.85
9NQ9	ELECTRON MICROSCOPY	2.97
9CUH	ELECTRON MICROSCOPY	3.03
7K4B	ELECTRON MICROSCOPY	3.1
7K4A	ELECTRON MICROSCOPY	3.26
9CUK	ELECTRON MICROSCOPY	3.26
9CUI	ELECTRON MICROSCOPY	3.42
6BO8	ELECTRON MICROSCOPY	3.6
7K4D	ELECTRON MICROSCOPY	3.66
7K4F	ELECTRON MICROSCOPY	3.75
7K4C	ELECTRON MICROSCOPY	3.78
6E2F	ELECTRON MICROSCOPY	3.9
6BO9	ELECTRON MICROSCOPY	4
6BOA	ELECTRON MICROSCOPY	4.2
6D7S	ELECTRON MICROSCOPY	4.34
7K4E	ELECTRON MICROSCOPY	4.34
6D7T	ELECTRON MICROSCOPY	4.44

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1D0-F1	80.76	0.53

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): 582

Post-translational modifications (2): 201, 742

Glycosylation sites (1): 398

Mutagenesis-validated functional residues (5):

Position	Phenotype
510	decreases channel opening, and thereby decreases channel activity.
523	decreases channel activity.
582	abolishes channel activity.
606	decreases channel opening, and thereby strongly decreases channel activity.
742	abolishes phosphorylation by pkc/prkca, achieves faster channel inactivation and no effect on binding to calmodulin.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 296 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_EXOCYTOSIS, GOBP_CALCIUM_ION_IMPORT, MARTIN_NFKB_TARGETS_UP, MARTIN_VIRAL_GPCR_SIGNALING_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP

GO Biological Process (10): calcium ion transport (GO:0006816), regulation of calcium ion-dependent exocytosis (GO:0017158), parathyroid hormone secretion (GO:0035898), response to calcium ion (GO:0051592), calcium ion homeostasis (GO:0055074), 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)

GO Molecular Function (6): calcium channel activity (GO:0005262), calmodulin binding (GO:0005516), identical protein binding (GO:0042802), metal ion binding (GO:0046872), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), 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
transport	2
protein binding	2
metal ion transport	1
calcium-ion regulated exocytosis	1
regulation of regulated secretory pathway	1
hormone secretion	1
response to metal ion	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
cation binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
membrane	1
cell periphery	1
cation channel complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPV6	S100G	P29377	878
TRPV6	ATP2B1	P20020	863
TRPV6	NIPSNAP1	Q9BPW8	860
TRPV6	TRPC1	P48995	844
TRPV6	S100A10	P08206	834
TRPV6	TRPM8	Q7Z2W7	751
TRPV6	TRPM4	Q8TD43	743
TRPV6	TRPM7	Q96QT4	743
TRPV6	TRPM6	Q9BX84	739
TRPV6	TRPC6	Q9Y210	720
TRPV6	PTH	P01270	715
TRPV6	TRPV5	Q9NQA5	712
TRPV6	GUSB	P08236	696
TRPV6	TRPC3	Q13507	695
TRPV6	KL	Q9UEF7	694

IntAct

123 interactions, top by confidence:

A	B	Type	Score
PTPN1	TRPV6	psi-mi:“MI:0203”(dephosphorylation reaction)	0.740
TRPV6	PTPN1	psi-mi:“MI:0915”(physical association)	0.740
PTPN1	TRPV6	psi-mi:“MI:0915”(physical association)	0.740
TRPV6	PARD3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	MPP7	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
PATJ	TRPV6	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN13	TRPV6	psi-mi:“MI:0407”(direct interaction)	0.440
TRPV6	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI3	TRPV6	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (22): TRPV6 (Two-hybrid), TRPV6 (Two-hybrid), TRPV6 (Two-hybrid), TRPV6 (Two-hybrid), TRPV6 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), TRPV6 (Two-hybrid), TRPV6 (Affinity Capture-MS), TRPV6 (Affinity Capture-Western), NUMB (Affinity Capture-Western), TRPV6 (Reconstituted Complex)

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

4 interactions.

A	Effect	B	Mechanism
PTPN1	down-regulates	TRPV6	dephosphorylation
PTPN1	“down-regulates activity”	TRPV6	dephosphorylation
PRKCB	“down-regulates activity”	TRPV6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	2e-06
Long-term potentiation	5	44.1×	3e-06
Assembly and cell surface presentation of NMDA receptors	8	37.6×	3e-09
Neurexins and neuroligins	9	32.8×	1e-09
Protein-protein interactions at synapses	5	24.6×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	78.5×	1e-14
protein localization to synapse	6	62.1×	6e-08
receptor clustering	7	59.0×	5e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	46.9×	2e-08
cell-cell adhesion	10	13.7×	2e-07
protein-containing complex assembly	7	10.8×	2e-04
chemical synaptic transmission	7	7.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	11
Uncertain significance	218
Likely benign	114
Benign	36

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
2708630	NM_018646.6(TRPV6):c.919C>T (p.Gln307Ter)	Pathogenic
3611582	NM_018646.6(TRPV6):c.520C>T (p.Arg174Ter)	Pathogenic
3630503	NM_018646.6(TRPV6):c.1685del (p.His562fs)	Pathogenic
3684592	NM_018646.6(TRPV6):c.697_698insGTAAGCTG (p.Asp233fs)	Pathogenic
3696047	NM_018646.6(TRPV6):c.43dup (p.Ala15fs)	Pathogenic
4695106	NM_018646.6(TRPV6):c.241C>T (p.Gln81Ter)	Pathogenic
4732474	NM_018646.6(TRPV6):c.282dup (p.Asp95fs)	Pathogenic
4799602	NM_018646.6(TRPV6):c.311dup (p.Leu104fs)	Pathogenic
4807289	NM_018646.6(TRPV6):c.881_882del (p.Val294fs)	Pathogenic
590765	NM_018646.6(TRPV6):c.530_533dup (p.Arg179fs)	Pathogenic
590769	NM_018646.6(TRPV6):c.978_979del (p.Gly327_Asp328insTer)	Pathogenic
590770	NM_018646.6(TRPV6):c.607+5G>A	Pathogenic
2572618	NM_018646.6(TRPV6):c.715_724del (p.Val239fs)	Likely pathogenic
2692409	NM_018646.6(TRPV6):c.254G>A (p.Trp85Ter)	Likely pathogenic
3620122	NM_018646.6(TRPV6):c.347-1G>A	Likely pathogenic
4077708	NM_018646.6(TRPV6):c.1657C>T (p.Gln553Ter)	Likely pathogenic
4294456	NM_018646.6(TRPV6):c.1570A>T (p.Lys524Ter)	Likely pathogenic
590767	NM_018646.6(TRPV6):c.1274G>A (p.Arg425Gln)	Likely pathogenic
590768	NM_018646.6(TRPV6):c.1352G>A (p.Gly451Glu)	Likely pathogenic
692130	NM_018646.6(TRPV6):c.635G>A (p.Cys212Tyr)	Likely pathogenic
692132	NM_018646.6(TRPV6):c.1447C>T (p.Arg483Trp)	Likely pathogenic
818220	NM_018646.6(TRPV6):c.1978G>C (p.Gly660Arg)	Likely pathogenic
932914	NM_018646.6(TRPV6):c.1646A>G (p.Tyr549Cys)	Likely pathogenic

SpliceAI

2484 predictions. Top by Δscore:

Variant	Effect	Δscore
7:142872365:CACT:C	donor_loss	1.0000
7:142872366:ACTC:A	donor_loss	1.0000
7:142872367:CT:C	donor_loss	1.0000
7:142872370:A:AC	donor_gain	1.0000
7:142872371:C:CC	donor_gain	1.0000
7:142872371:CCG:C	donor_gain	1.0000
7:142872403:C:CA	donor_gain	1.0000
7:142872474:ACAAT:A	acceptor_gain	1.0000
7:142872475:CAAT:C	acceptor_gain	1.0000
7:142872475:CAATC:C	acceptor_gain	1.0000
7:142872476:AAT:A	acceptor_gain	1.0000
7:142872477:AT:A	acceptor_gain	1.0000
7:142872477:ATCTG:A	acceptor_loss	1.0000
7:142872479:C:CC	acceptor_gain	1.0000
7:142872482:C:CT	acceptor_gain	1.0000
7:142872483:G:C	acceptor_gain	1.0000
7:142872483:G:GC	acceptor_gain	1.0000
7:142872485:A:AC	acceptor_gain	1.0000
7:142872485:A:C	acceptor_gain	1.0000
7:142872492:C:CT	acceptor_gain	1.0000
7:142872493:A:T	acceptor_gain	1.0000
7:142873446:ACCTG:A	donor_loss	1.0000
7:142873447:C:T	donor_loss	1.0000
7:142874486:CTGA:C	donor_loss	1.0000
7:142874487:TGAC:T	donor_loss	1.0000
7:142874488:GACC:G	donor_loss	1.0000
7:142874490:C:CT	donor_loss	1.0000
7:142874490:CCTT:C	donor_gain	1.0000
7:142874652:TGATG:T	acceptor_gain	1.0000
7:142874653:GATG:G	acceptor_gain	1.0000

AlphaMissense

5004 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:142874116:G:C	F533L	0.997
7:142874116:G:T	F533L	0.997
7:142874118:A:G	F533L	0.997
7:142874559:A:G	W502R	0.997
7:142874559:A:T	W502R	0.997
7:142874083:A:C	F544L	0.996
7:142874083:A:T	F544L	0.996
7:142874085:A:G	F544L	0.996
7:142873518:A:G	L613P	0.995
7:142873629:A:G	L576P	0.995
7:142873520:G:C	N612K	0.994
7:142873520:G:T	N612K	0.994
7:142873550:A:C	F602L	0.994
7:142873550:A:T	F602L	0.994
7:142873552:A:G	F602L	0.994
7:142874088:C:G	G543R	0.991
7:142873530:A:G	L609P	0.990
7:142873530:A:T	L609H	0.989
7:142874087:C:T	G543D	0.989
7:142874517:C:G	G516R	0.989
7:142873640:G:C	S572R	0.988
7:142873640:G:T	S572R	0.988
7:142873642:T:G	S572R	0.988
7:142874126:A:G	L530P	0.988
7:142875629:A:G	W361R	0.988
7:142875629:A:T	W361R	0.988
7:142873625:G:C	F577L	0.987
7:142873625:G:T	F577L	0.987
7:142873627:A:G	F577L	0.987
7:142873700:G:C	F552L	0.987

dbSNP variants (sampled 300 via entrez): RS1000394543 (7:142885596 C>T), RS1000448482 (7:142886629 C>T), RS1000642681 (7:142871323 C>T), RS1000711249 (7:142881114 T>C), RS1000751247 (7:142876123 C>G,T), RS1000984448 (7:142882502 G>A,C,T), RS1001464286 (7:142879492 T>C,G), RS1001670606 (7:142873730 G>T), RS1001734798 (7:142885659 C>T), RS1001748097 (7:142871672 G>A,C), RS1002439494 (7:142882793 C>A), RS1002613382 (7:142883101 G>A), RS1002664042 (7:142876531 G>A,T), RS1002751215 (7:142873062 T>C), RS1002802183 (7:142873486 G>A)

Disease associations

OMIM: gene MIM:606680 | disease phenotypes: MIM:618188, MIM:167800

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperparathyroidism, transient neonatal	Strong	Autosomal recessive
intestinal hypomagnesemia 1	Strong	Autosomal recessive
hereditary chronic pancreatitis	Strong	Autosomal dominant
pancreatitis	Moderate	Autosomal dominant
neonatal severe primary hyperparathyroidism	Supportive	Autosomal recessive

Mondo (6): hyperparathyroidism, transient neonatal (MONDO:0032591), hereditary chronic pancreatitis (MONDO:0008185), hyperparathyroidism (MONDO:0001741), pancreatitis (MONDO:0004982), intestinal hypomagnesemia 1 (MONDO:0011176), neonatal severe primary hyperparathyroidism (MONDO:0009397)

Orphanet (1): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000105	Enlarged kidney
HP:0000122	Unilateral renal agenesis
HP:0000138	Ovarian cyst
HP:0000248	Brachycephaly
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000750	Delayed speech and language development
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000819	Diabetes mellitus
HP:0000820	Abnormality of the thyroid gland
HP:0000843	Hyperparathyroidism
HP:0000883	Thin ribs
HP:0000938	Osteopenia
HP:0000944	Abnormal metaphysis morphology
HP:0000952	Jaundice
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001297	Stroke
HP:0001334	Communicating hydrocephalus
HP:0001344	Absent speech
HP:0001537	Umbilical hernia
HP:0001561	Polyhydramnios
HP:0001643	Patent ductus arteriosus
HP:0001744	Splenomegaly
HP:0001974	Increased total leukocyte count

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004860_42	Alcoholic chronic pancreatitis	2.000000e-06
GCST005275_22	Cancer	3.000000e-07
GCST009837_6	Anxiety	3.000000e-08
GCST011383_14	Mastocytosis	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009863	anxiety measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D006961	Hyperparathyroidism	C19.642.355
D010195	Pancreatitis	C06.689.750
C537262	Hereditary pancreatitis (supp.)
C563375	Hyperparathyroidism, Neonatal Severe Primary (supp.)
C566593	Hypomagnesemia 1, Intestinal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1628465 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,716 (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
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884
CHEMBL4228250	SOR-C13	1	19

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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
GSK3527497	Inhibition	7.92	pIC50
SOR-C13	Inhibition	7.85	pIC50
acetaldehyde	Activation	6.7	pEC50
TRPV6 inhibitor cis-22 a	Inhibition	6.52	pIC50
tetrahydrocannabivarin	Inhibition	5.05	pIC50
ruthenium red	Antagonist	5.0	pIC50
ethanol	Activation	0.82	pEC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5542330	IC50	9400 nM

ChEMBL bioactivities

48 potent at pChembl≥5 of 109 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.85	IC50	14	nM	SOR-C13
7.30	IC50	50	nM	CHEMBL4435596
7.19	IC50	64	nM	CHEMBL4796516
7.09	IC50	82	nM	CHEMBL4777551
6.89	IC50	130	nM	CHEMBL4789936
6.89	IC50	130	nM	CHEMBL5518142
6.82	IC50	150	nM	CHEMBL4740003
6.77	IC50	170	nM	CHEMBL4760109
6.72	IC50	190	nM	CHEMBL5542781
6.51	IC50	310	nM	CHEMBL5543003
6.50	IC50	320	nM	CHEMBL4435596
6.43	IC50	370	nM	CHEMBL4762249
6.37	IC50	430	nM	CHEMBL4761058
6.36	IC50	440	nM	CHEMBL5556793
6.26	IC50	550	nM	CHEMBL4746237
6.26	IC50	550	nM	CHEMBL4475503
6.24	IC50	570	nM	CHEMBL5557326
6.22	IC50	600	nM	CHEMBL4470714
6.22	IC50	600	nM	CHEMBL4448267
6.22	IC50	600	nM	CHEMBL4789446
6.16	IC50	690	nM	CHEMBL4742895
6.00	IC50	1000	nM	CHEMBL5555456
5.80	IC50	1600	nM	CHEMBL4789968
5.77	IC50	1700	nM	CHEMBL4579017
5.77	IC50	1700	nM	CHEMBL4475503
5.77	IC50	1700	nM	CHEMBL5517726
5.70	IC50	2000	nM	CHEMBL5559359
5.68	IC50	2100	nM	CHEMBL4792477
5.62	IC50	2400	nM	CHEMBL4790237
5.62	IC50	2400	nM	CHEMBL4749205
5.55	IC50	2840	nM	CHEMBL5532006
5.50	IC50	3130	nM	CHEMBL5532025
5.50	IC50	3130	nM	CHEMBL5517874
5.38	IC50	4200	nM	CHEMBL5512439
5.36	IC50	4390	nM	ECONAZOLE
5.29	IC50	5100	nM	CHEMBL5557022
5.28	IC50	5200	nM	CHEMBL2386186
5.28	IC50	5300	nM	CHEMBL5555589
5.27	IC50	5400	nM	CHEMBL2386186
5.24	IC50	5800	nM	CHEMBL5559197
5.21	IC50	6200	nM	CHEMBL5512512
5.03	IC50	9400	nM	TETRAHYDROCANNABIVARIN
5.03	IC50	9400	nM	CHEMBL5542330
5.02	IC50	9600	nM	CHEMBL5558268
5.01	IC50	9800	nM	CHEMBL2386185
5.01	IC50	9700	nM	CHEMBL2386184
5.00	IC50	1e+04	nM	CHEMBL2386183

PubChem BioAssay actives

48 with measured affinity, of 165 total; 39 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
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-4-(diaminomethylideneamino)butyl]carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2,6-diaminohexanoyl]amino]-5-oxopentanoic acid	1388445: Inhibition of TRPV6 (unknown origin) expressed in HEK293 cells by whole cell patch clamp assay	ic50	0.0140	uM
1-[4-(3-methylphenyl)cyclohexyl]-4-pyridin-3-ylpiperazine	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.0500	uM
5-[[4-[4-[3-(trifluoromethyl)phenyl]cyclohexyl]piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.0640	uM
5-[[4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]cyclohexyl]piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.0820	uM
5-[[4-[4-hydroxy-4-[2-(trifluoromethyl)phenyl]cyclohexyl]piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.1300	uM
1-[4-(2-methoxyphenyl)cyclohexyl]-4-pyridin-3-ylpiperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	0.1300	uM
5-[[4-[4-(3-methylphenyl)cyclohexyl]piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.1500	uM
1-[(6-bromo-3-pyridinyl)methyl]-4-(4-phenylcyclohexyl)piperazine	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.1700	uM
1-[(1S,4S)-4-phenylcycloheptyl]-4-(pyridin-3-ylmethyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	0.1900	uM
1-[4-(3-methylphenyl)cyclohexyl]-4-(pyridin-3-ylmethyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	0.3100	uM
5-[[4-(4-phenylcyclohexyl)piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.3700	uM
(4-hydroxy-3-methoxyphenyl)-[4-(4-phenylcyclohexyl)piperazin-1-yl]methanone	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.4300	uM
(2R)-2-[(4-chlorophenyl)methoxymethyl]-1-[2-(4-methoxyphenyl)ethyl]pyrrolidine	2062699: Inhibition of TRPV6 (unknown origin)	ic50	0.4400	uM
1-[(6-methoxy-3-pyridinyl)methyl]-4-(4-phenylcyclohexyl)piperazine	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.5500	uM
1-(4-phenylcyclohexyl)-4-(pyridin-3-ylmethyl)piperazine	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.5500	uM
1-[4-(2-chlorophenyl)cyclohexyl]-4-pyridin-3-ylpiperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	0.5700	uM
phenyl-[5-[[4-(4-phenylcyclohexyl)piperazin-1-yl]methyl]-2-pyridinyl]diazene	1511976: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction of Cd2+ influx preincubated for 5 mins followed by CdCl2 addition measured under dark state by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.6000	uM
5-[4-(4-phenylcyclohexyl)piperazine-1-carbonyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.6000	uM
5-[[4-[4-[2-(trifluoromethyl)phenyl]cyclohexyl]piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	0.6900	uM
1-(4-phenylcyclohexyl)-4-(pyridin-4-ylmethyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	1.0000	uM
2-methoxy-4-[[4-(4-phenylcyclohexyl)piperazin-1-yl]methyl]phenol	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	1.6000	uM
phenyl-[4-[[4-(4-phenylcyclohexyl)piperazin-1-yl]methyl]phenyl]diazene	1511979: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx preincubated for 5 mins followed by CdCl2 addition using 365 nm UV-light irradiated compound by calcium-5 fluorescence dye-based FLIPR assay	ic50	1.7000	uM
1-(furan-2-yl)-2-[4-(4-phenylcyclohexyl)piperazin-1-yl]ethanone	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	1.7000	uM
2-[4-(4-phenylcyclohexyl)piperazin-1-yl]-1-pyridin-4-ylethanone	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	2.0000	uM
[4-(4-tert-butylcyclohexyl)piperazin-1-yl]-(4-hydroxy-3-methoxyphenyl)methanone	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	2.1000	uM
4-[[4-(4-tert-butylcyclohexyl)piperazin-1-yl]methyl]-2-methoxyphenol	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	2.4000	uM
5-[[4-(4-tert-butylcyclohexyl)piperazin-1-yl]methyl]-1H-pyridin-2-one	1685517: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay	ic50	2.4000	uM
1-[(1S,4R)-4-phenylcycloheptyl]-4-(pyridin-3-ylmethyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	3.1300	uM
2-[4-(4-phenylcyclohexyl)piperazin-1-yl]-1-pyridin-3-ylethanone	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	4.2000	uM
Econazole	2062704: Inhibition of human TRPV6 expressed in baculovirus infected Sf9 cells	ic50	4.3900	uM
1-[(4-nitrophenyl)methyl]-4-(4-phenylcyclohexyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	5.1000	uM
2-(4-iodophenyl)-2-phenyl-1-oxa-3-azonia-2-boranuidacyclopentane	749404: Inhibition of human TRPV6 transfected in HEK293 cells assessed as inhibition of Cd2+ influx after 5 mins by FLIPR assay	ic50	5.2000	uM
1-(4-phenylcyclohexyl)-4-(pyridin-2-ylmethyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	5.3000	uM
1-(1,3-benzodioxol-5-ylmethyl)-4-(4-phenylcyclohexyl)piperazine	2062703: Inhibition of human TRPV6 (1 to 725 residues) by FLIPR analysis	ic50	5.8000	uM
(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,10a-dihydrobenzo[c]chromen-1-ol	2062705: Inhibition of TRPV6 (unknown origin) expressed in Sf9 cells	ic50	9.4000	uM
(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol	1845624: Inhibition of TRPV6 channel (unknown origin) by Patch-clamp assay	ic50	9.4000	uM
(4-chlorophenyl)-phenylborinic acid	749405: Inhibition of human TRPV6 transfected in HEK293 cells assessed as inhibition of Ca2+ influx after 5 mins by FLIPR assay	ic50	9.7000	uM
2-(4-bromophenyl)-2-phenyl-1-oxa-3-azonia-2-boranuidacyclopentane	749404: Inhibition of human TRPV6 transfected in HEK293 cells assessed as inhibition of Cd2+ influx after 5 mins by FLIPR assay	ic50	9.8000	uM
2-(5-methylthiophen-2-yl)-2-phenyl-1-oxa-3-azonia-2-boranuidacyclopentane	749404: Inhibition of human TRPV6 transfected in HEK293 cells assessed as inhibition of Cd2+ influx after 5 mins by FLIPR assay	ic50	10.0000	uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Calcitriol	decreases reaction, affects reaction, affects cotreatment, affects binding, increases activity (+2 more)	8
Calcium	decreases reaction, increases uptake, increases abundance, increases reaction, increases transport	4
perfluorooctanoic acid	decreases reaction, increases expression, decreases expression	2
lithocholic acid acetate	affects binding, increases activity, increases expression	2
Barium	increases uptake	2
Cadmium	decreases reaction, increases import, increases uptake	2
Lithocholic Acid	affects binding, increases activity, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
4-O-methyl-12-O-tetradecanoylphorbol 13-acetate	decreases reaction, increases uptake	1
3,4,5,3’,4’-pentachlorobiphenyl	affects cotreatment, decreases expression	1
1,25-dihydroxy-26,27-dimethylcholecalciferol	affects binding, increases activity, increases expression	1
calphostin C	decreases reaction, increases uptake	1
perfluorooctane sulfonic acid	decreases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
1,25-dihydroxyvitamin D	decreases reaction, increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
25-hydroxyvitamin D	increases expression, increases reaction	1
2-aminoethoxydiphenyl borate	decreases reaction, increases import	1
perfluorohexanesulfonic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	1
Capsaicin	increases abundance, increases reaction, increases expression, increases response to substance	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2388391	Binding	Inhibition of human TRPV6 transfected in HEK293 cells assessed as inhibition of Cd2+ influx after 5 mins by FLIPR assay	Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8ET	Ubigene BeWo TRPV6 KO	Cancer cell line	Male
CVCL_TU88	HAP1 TRPV6 (-) 1	Cancer cell line	Male
CVCL_XU76	HAP1 TRPV6 (-) 2	Cancer cell line	Male
CVCL_XU77	HAP1 TRPV6 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00318994	PHASE4	COMPLETED	Evaluation of Pancreatic Tissue Penetration of Meronem® in the Prophylaxis of Septic Complications in Severe Pancreatitis
NCT00428025	PHASE4	TERMINATED	Diclofenac for the Prevention of Post-ERCP Pancreatitis in Higher Risk Patients
NCT00786929	PHASE4	COMPLETED	Acute Pancreatitis and Acute Fluid Collections
NCT00999232	PHASE4	COMPLETED	Assess the Effect of Erythromycin on the Rate of Success in Placement of a Self-propelled Feeding Tube
NCT01070680	PHASE4	COMPLETED	Dexmedetomidine Versus Placebo in Endoscopic Retrograde Cholangiopancreatography (ERCP) Sedation
NCT01132521	PHASE4	SUSPENDED	Ulinastatin in Severe Acute Pancreatitis
NCT01186562	PHASE4	COMPLETED	Sitagliptin Therapy to Improve Outcomes After Islet Autotransplant
NCT01744847	PHASE4	COMPLETED	DGT Versus TPS in Patients With Initial PD Cannulation by Chance; Prospective Multi-center Study
NCT01784445	PHASE4	COMPLETED	Post ERCP Pancreatitis Prevention in Average Risk Patients
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02465138	PHASE4	WITHDRAWN	A Randomized Controlled Trial of IV Ketorolac to Prevent Post-ERCP Pancreatitis
NCT02797067	PHASE4	COMPLETED	Rectal Indomethacin to Prevent Post ESWL-pancreatitis
NCT05659147	PHASE4	ENROLLING_BY_INVITATION	Imaging Biomarkers of Pancreatic Function and Disease
NCT07024199	PHASE4	RECRUITING	Comparison of the Effectiveness of Paracetamol With Ibuprofen or Paracetamol With Metamizole in Treating Pain in Acute Pancreatitis in Children
NCT07083063	PHASE4	RECRUITING	Precise Endoscopic Application of Nitroglycerin in Preventing Post-ERCP Pancreatitis
NCT07262957	PHASE4	RECRUITING	Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
NCT00037518	PHASE4	COMPLETED	A Study of an Investigational Medication for Severe Primary Hyperparathyroidism or Parathyroid Cancer
NCT00359385	PHASE4	WITHDRAWN	The Effects of Alendronate After Cure of Primary Hyperparathyroidism
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT01143987	PHASE4	COMPLETED	Cincalcet and Vascular Arterial Stiffness Among Peritoneal Dialysis Patients With Secondary Hyperparathyroidism
NCT01573520	PHASE4	COMPLETED	Treatment Adhesion in Dialysis Patients Treated With Cinacalcet
NCT00121901	PHASE3	COMPLETED	Does Glyceryl Nitrate Prevent Post-Endoscopic Retrograde Cholangiopancreaticography (ERCP) Pancreatitis?
NCT00142233	PHASE3	COMPLETED	EUROPAC-2 - Pain Treatment of Hereditary and Idiopathic Pancreatitis
NCT00210938	PHASE3	COMPLETED	Doripenem in the Treatment of Complicated Intra-Abdominal Infections
NCT00229060	PHASE3	COMPLETED	Doripenem in the Treatment of Complicated Intra-Abdominal Infections
NCT00660335	PHASE3	COMPLETED	Safety and Efficacy of Synthetic Human Secretin-Enhanced MRCP in Subjects With Abnormalities of the Pancreas
NCT02573389	PHASE3	SUSPENDED	Pancreatic Duct Stenting to Prevent Postoperative Pancreatic Fistula (POPF) After Distal Pancreatectomy
NCT02821546	PHASE3	COMPLETED	Aggressive Fluid Hydration for the Prevention of Post-ERCP Pancreatitis
NCT04021498	PHASE3	TERMINATED	Simvastatin in the Prevention of Recurrent Pancreatitis
NCT06691893	PHASE3	RECRUITING	Evaluating the Efficacy of RELiZORB in Managing Exocrine Pancreatic Insufficiency in Tube-fed Pancreatitis Patients
NCT07599605	PHASE3	COMPLETED	Prophylaxis Against Post-Endoscopic Retrograde Cholangio-Pancreatography Pancreatitis.
NCT00417612	PHASE3	COMPLETED	Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
NCT00527267	PHASE3	COMPLETED	Safety and Efficacy Study of AMG 073 in Hemodialysis Subjects
NCT00975000	PHASE3	COMPLETED	Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients
NCT01191762	PHASE3	COMPLETED	Sevelamer and Secondary Hyperparathyroidism in Chronic Kidney Disease
NCT01277510	PHASE3	TERMINATED	Pediatric Chronic Kidney Disease Safety and Efficacy
NCT04040946	PHASE3	COMPLETED	Trial Comparing 2 Diagnostic Strategies for Preoperative Localization of Parathyroid Adenoma in Primary Hyperparathyroidism:TEMP / CT With Tc99m-sestaMIBI or PET / CT With F18-choline in First Intention
NCT00040131	PHASE2	TERMINATED	Safety and Efficacy Study of IL-10 (Tenovil TM) in the Prevention of Post-ERCP Acute Pancreatitis (Study P02580)(TERMINATED)
NCT01460615	PHASE2	COMPLETED	Cortisone Treatment for the Prevention of Postoperative Pancreatitis and Pancreatitis-induced Complications After Pancreaticoduodenectomy and Distal Pancreatic Resection