TRPV6

Chr 7AR

transient receptor potential cation channel subfamily V member 6

Also known as: ABP/ZF, CAT1, CATL, ECAC2, HRPTTN, HSA277909, LP6728, ZFAB

NCBI Gene: 55503ENSG00000165125UniProt: Q9H1D0

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. [provided by RefSeq, Feb 2015]

Primary Disease Associations & Inheritance

Hyperparathyroidism, transient neonatalMIM #618188
AR
294
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRPV6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 168 VUS of 294 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.000
Z-score 3.19
OE 0.44 (0.30–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.38Z-score
OE missense 0.82 (0.75–0.89)
365 obs / 447.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.30–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.75–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 17 / 38.3Missense obs/exp: 365 / 447.2Syn Z: 0.77

ClinVar Variant Classifications

294 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS168
Likely Benign96
Benign12
14
Pathogenic
4
Likely Pathogenic
168
VUS
96
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
8
0
14
Likely Pathogenic
2
0
2
0
4
VUS
2
155
9
2
168
Likely Benign
0
2
44
50
96
Benign
0
1
9
2
12
Total101587254294

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRPV6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TRPV6-related transient neonatal hyperparathyroidism

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperparathyroidism, transient neonatal

MIM #618188

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TRPV6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Advances in acute and chronic pancreatitis.
Strum WB et al.·World J Gastroenterol
2023Review
TRPV6 channels.
Fecher-Trost C et al.·Handb Exp Pharmacol
2014Review
Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel.
Walker V et al.·Adv Clin Chem
2023Review
Targeting TRPV6/CXCR4 complexes prevents castration-resistant prostate cancer metastasis to the bone.
Cordier C et al.·Signal Transduct Target Ther
2025
The potential of TRP channels as new prognostic and therapeutic targets against prostate cancer progression.
Chinigò G et al.·Biochim Biophys Acta Rev Cancer
2024Review
An overlooked African gene variant linked to the calcium selective channel TRPV6: A mini-review.
Hilliard CB·Gene
2023Review
TRP channels in the digestive system.
Holzer P·Curr Pharm Biotechnol
2011Review
Roles of Ion Fluxes, Metabolism, and Redox Balance in Cancer Therapy.
Lai HL et al.·Antioxid Redox Signal
2021Review
TRPV6-related pancreatitis: natural history and the impact of the pancreas-specific deletion on pancreatitis in mice.
Masamune A et al.·J Gastroenterol
2026Natural history
The Coexistence of TRPV6 Variants With Other Pancreatitis-Associated Genes Affects Pediatric-Onset Pancreatitis.
Hirai S et al.·J Pediatr Gastroenterol Nutr
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools