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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TRPV6
transient receptor potential cation channel subfamily V member 6
Chromosome 7 Β· 7q34
NCBI Gene: 55503Ensembl: ENSG00000165125.22HGNC: HGNC:14006UniProt: Q9H1D0
141PubMed Papers
21Diseases
0Drugs
24Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
calmodulin bindingcalcium ion transmembrane transportcalcium ion import across plasma membraneplasma membranehyperparathyroidism, transient neonatalneonatal severe primary hyperparathyroidismpancreas diseaseacute pancreatitis
✦AI Summary

TRPV6 is a highly calcium-selective cation channel essential for transcellular calcium transport in epithelial tissues including intestine, kidney, placenta, and pancreas 1. Unlike most TRP channels, TRPV6 exhibits exceptional selectivity for Ca2+ ions and functions as a calcium entry channel in the first step of calcium absorption and reabsorption pathways 2. The channel is activated by low intracellular calcium levels and employs complex inactivation mechanisms involving both rapid calcium-dependent and slower calmodulin-dependent processes 3. Transcriptional expression is primarily regulated by 1,25-dihydroxyvitamin D3, with additional calcium-dependent control mechanisms 4. Loss-of-function mutations in TRPV6 cause transient neonatal hyperparathyroidism and early-onset chr7 pancreatitis, with skeletal dysplasia observed in severe cases 5. TRPV6 dysfunction also results in hypercalciuria, reduced bone density, and impaired male fertility 1. Conversely, TRPV6 is significantly upregulated in prostate and breast cancers, where elevated expression correlates with tumor aggressiveness and poor prognosis 6. These findings establish TRPV6 as critical for calcium homeostasis and identify it as both a biomarker and potential therapeutic target in malignancies.

Sources cited
1
TRPV6 structure, function, tissue expression, vitamin D regulation, loss-of-function phenotypes, and cancer overexpression
PMID: 35031425
2
TRPV6 calcium selectivity, transcellular transport role, tissue distribution, and vitamin D responsiveness
PMID: 21290300
3
TRPV6 calcium selectivity, unique features including ACG initiation codon, and cancer upregulation
PMID: 24756713
4
TRPV6 evolutionary context, loss-of-function mutations causing hyperparathyroidism and pancreatitis, species-specific differences
PMID: 33964462
5
TRPV6 as epithelial calcium channel, vitamin D transcriptional control, calcium selectivity, and cancer progression link
PMID: 17217060
6
TRPV6 overexpression in prostate and breast cancers and role in cancer pathogenesis
PMID: 21290334
Disease Associationsβ“˜21
hyperparathyroidism, transient neonatalOpen Targets
0.80Strong
neonatal severe primary hyperparathyroidismOpen Targets
0.37Weak
pancreas diseaseOpen Targets
0.29Weak
acute pancreatitisOpen Targets
0.28Weak
hyperparathyroidismOpen Targets
0.27Weak
Slender long boneOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
chronic pancreatitisOpen Targets
0.19Weak
preeclampsiaOpen Targets
0.17Weak
hereditary chronic pancreatitisOpen Targets
0.12Weak
myotonic syndromeOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
azoospermiaOpen Targets
0.09Suggestive
Deltaretrovirus InfectionsOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
rheumatoid arthritisOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
Hyperparathyroidism, transient neonatalUniProt
Pathogenic Variants24
NM_018646.6(TRPV6):c.762_765del (p.Gln254fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 254
NM_018646.6(TRPV6):c.1352G>A (p.Gly451Glu)Likely pathogenic
Hyperparathyroidism, transient neonatal|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 451
NM_018646.6(TRPV6):c.530_533dup (p.Arg179fs)Pathogenic
Hyperparathyroidism, transient neonatal|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 179
NM_018646.6(TRPV6):c.282dup (p.Asp95fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 95
NM_018646.6(TRPV6):c.241C>T (p.Gln81Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 81
NM_018646.6(TRPV6):c.311dup (p.Leu104fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 104
NM_018646.6(TRPV6):c.881_882del (p.Val294fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 294
NM_018646.6(TRPV6):c.43dup (p.Ala15fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 15
NM_018646.6(TRPV6):c.347-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_018646.6(TRPV6):c.520C>T (p.Arg174Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 174
NM_018646.6(TRPV6):c.1685del (p.His562fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 562
NM_018646.6(TRPV6):c.1657C>T (p.Gln553Ter)Likely pathogenic
Hyperparathyroidism, transient neonatal
β˜…β˜†β˜†β˜†2024β†’ Residue 553
NM_018646.6(TRPV6):c.697_698insGTAAGCTG (p.Asp233fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 233
NM_018646.6(TRPV6):c.919C>T (p.Gln307Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 307
NM_018646.6(TRPV6):c.715_724del (p.Val239fs)Likely pathogenic
Hyperparathyroidism, transient neonatal
β˜…β˜†β˜†β˜†2022β†’ Residue 239
NM_018646.6(TRPV6):c.1646A>G (p.Tyr549Cys)Likely pathogenic
Hyperparathyroidism, transient neonatal
β˜…β˜†β˜†β˜†2020β†’ Residue 549
NM_018646.6(TRPV6):c.1274G>A (p.Arg425Gln)Likely pathogenic
Hyperparathyroidism, transient neonatal
β˜…β˜†β˜†β˜†2019β†’ Residue 425
NM_018646.6(TRPV6):c.1447C>T (p.Arg483Trp)Likely pathogenic
Hyperparathyroidism, transient neonatal
β˜…β˜†β˜†β˜†2019β†’ Residue 483
NM_018646.6(TRPV6):c.635G>A (p.Cys212Tyr)Likely pathogenic
Hyperparathyroidism, transient neonatal
β˜…β˜†β˜†β˜†2019β†’ Residue 212
NM_018646.6(TRPV6):c.1978G>C (p.Gly660Arg)Likely pathogenic
Slender long bone;Hyperparathyroidism;Embryonic calcium dysregulation;Metaphyseal fractures
β˜…β˜†β˜†β˜†2018β†’ Residue 660
View on ClinVar β†—
Related Genes
ATP2B1Protein interaction98%CALM2Protein interaction98%KCNN4Protein interaction98%NIPSNAP1Protein interaction86%PTHProtein interaction80%TRPM6Protein interaction79%
Tissue Expression6 tissues
Liver
100%
Brain
65%
Bone Marrow
23%
Lung
10%
Ovary
9%
Heart
5%
Gene Interaction Network
Click a node to explore
TRPV6ATP2B1CALM2KCNN4NIPSNAP1PTHTRPM6
PROTEIN STRUCTURE
Preparing viewer…
PDB7S8B Β· 2.43 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.64LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.49 [0.38–0.64]
RankingsWhere TRPV6 stands among ~20K protein-coding genes
  • #3,267of 20,598
    Most Researched141 Β· top quartile
  • #2,007of 5,498
    Most Pathogenic Variants24
  • #4,547of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedTRPV6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Advances in acute and chronic pancreatitis.
PMID: 36926670
World J Gastroenterol Β· 2023
1.00
2
Human TRPV6-pathies caused by gene mutations.
PMID: 33610740
Biochim Biophys Acta Gen Subj Β· 2021
0.90
3
TRPV6 channels.
PMID: 24756713
Handb Exp Pharmacol Β· 2014
0.80
4
TRPV6.
PMID: 17217060
Handb Exp Pharmacol Β· 2007
0.70
5
PMID: 30299660
0.60