TRPV6

transient receptor potential cation channel subfamily V member 6, the group of Transient receptor potential cation channels|Ankyrin repeat domain containing

Basic information

Region (hg38): 7:142871208-142885745

Previous symbols: [ "ECAC2" ]

Links

ENSG00000165125 ∙ NCBI:55503 ∙ OMIM:606680 ∙ HGNC:14006 ∙ Uniprot:Q9H1D0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal severe primary hyperparathyroidism (Supportive), mode of inheritance: AR
• hyperparathyroidism, transient neonatal (Moderate), mode of inheritance: AR
• intestinal hypomagnesemia 1 (Strong), mode of inheritance: AR
• pancreatitis (Moderate), mode of inheritance: AD
• hyperparathyroidism, transient neonatal (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperparathyroidism, transient neonatal	AR	Musculoskeletal	Individuals can present in early life with fractures, respiratory and feeding difficulties, and management with oral calcium has shown to be beneficial	Musculoskeletal	29861107

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPV6 gene.

• not_provided (217 variants)
• Inborn_genetic_diseases (82 variants)
• Hyperparathyroidism,_transient_neonatal (22 variants)
• TRPV6-related_disorder (14 variants)
• Embryonic_calcium_dysregulation (1 variants)
• Metaphyseal_fractures (1 variants)
• Slender_long_bone (1 variants)
• Hereditary_pancreatitis (1 variants)
• Hyperparathyroidism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPV6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018646.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	44	12	59
missense		8	155	7	1	171
nonsense	2	3				5
start loss						0
frameshift	6	1				7
splice donor/acceptor (+/-2bp)		1				1
Total	8	13	158	51	13

Highest pathogenic variant AF is 0.00008240029

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPV6	protein_coding	protein_coding	ENST00000359396	15	14552

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.17e-7	1.00	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	365	447	0.816	0.0000280	4724
Missense in Polyphen		103	149.91	0.68707		1673
Synonymous	0.770	160	173	0.925	0.0000101	1453
Loss of Function	3.19	17	38.3	0.444	0.00000209	387

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000198	0.000193
Middle Eastern	0.000544	0.000544
South Asian	0.000524	0.000523
Other	0.000518	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:11097838, PubMed:11278579, PubMed:11248124 PubMed:15184369, PubMed:23612980, PubMed:29258289). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:15184369). 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. {ECO:0000250|UniProtKB:Q91WD2, ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:11278579, ECO:0000269|PubMed:15184369, ECO:0000269|PubMed:23612980, ECO:0000269|PubMed:29258289}.
• Pathway: Salivary secretion - Homo sapiens (human);Mineral absorption - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;Vitamin D Receptor Pathway;Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels;TCR signaling in naïve CD8+ T cells;Signaling events mediated by PTP1B;TCR signaling in naïve CD4+ T cells (Consensus)

Intolerance Scores

• loftool: 0.351
• rvis_EVS: -0.68
• rvis_percentile_EVS: 15.36

Haploinsufficiency Scores

• pHI: 0.0589
• hipred: N
• hipred_score: 0.420
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.727

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trpv6
• Phenotype: cellular phenotype; reproductive system phenotype

Zebrafish Information Network

• Gene name: trpv6
• Affected structure: corpuscles of Stannius
• Phenotype tag: abnormal
• Phenotype quality: cellular quality

Gene ontology

• Biological process: calcium ion transport;regulation of calcium ion-dependent exocytosis;response to calcium ion;calcium ion homeostasis;calcium ion transmembrane transport;calcium ion import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: ion channel activity;calcium channel activity;protein binding;calmodulin binding;metal ion binding