TRPV3

transient receptor potential cation channel subfamily V member 3, the group of Transient receptor potential cation channels|Ankyrin repeat domain containing

Basic information

Region (hg38): 17:3510502-3557812

Links

ENSG00000167723

∙ NCBI:162514 ∙ OMIM:607066 ∙ HGNC:18084 ∙ Uniprot:Q8NET8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Olmsted syndrome 1 (Strong), mode of inheritance: AD
mutilating palmoplantar keratoderma with periorificial keratotic plaques (Strong), mode of inheritance: AD
mutilating palmoplantar keratoderma with periorificial keratotic plaques (Supportive), mode of inheritance: AD
isolated focal non-epidermolytic palmoplantar keratoderma (Supportive), mode of inheritance: AD
mutilating palmoplantar keratoderma with periorificial keratotic plaques (Strong), mode of inheritance: AD
isolated focal non-epidermolytic palmoplantar keratoderma (Limited), mode of inheritance: Unknown
Olmsted syndrome 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Olmsted syndrome 1; Palmoplantar keratoderma, nonepidermolytic focal 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	22405088; 25285920
Infections and skin cancer have been described at arising at the site of skin lesions

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPV3 gene.

not_provided (156 variants)
Inborn_genetic_diseases (118 variants)
Isolated_focal_non-epidermolytic_palmoplantar_keratoderma (81 variants)
TRPV3-related_disorder (16 variants)
Olmsted_syndrome_1 (14 variants)
not_specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPV3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000145068.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	38 clinvar	14 clinvar	55
missense	8 clinvar	2 clinvar	153 clinvar	20 clinvar	11 clinvar	194
nonsense			2 clinvar		1 clinvar	3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar		1 clinvar	3
Total	8	2	160	58	27

Highest pathogenic variant AF is 0.0000123914

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPV3	protein_coding	protein_coding	ENST00000301365	17	47494

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.60e-20	0.0197	125531	0	217	125748	0.000863

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.171	467	478	0.978	0.0000289	5192
Missense in Polyphen		126	146.62	0.85936		1622
Synonymous	-0.310	215	209	1.03	0.0000144	1518
Loss of Function	0.823	33	38.5	0.857	0.00000202	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000844	0.000844
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00218	0.00218
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00126	0.00125
Middle Eastern	0.00218	0.00218
South Asian	0.000331	0.000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). {ECO:0000269|PubMed:12077604, ECO:0000269|PubMed:12077606, ECO:0000269|PubMed:21593771}.;
Disease: DISEASE: Palmoplantar keratoderma, non-epidermolytic, focal 2 (FNEPPK2) [MIM:616400]: A dermatological disorder characterized by non-epidermolytic, abnormal thickening of the skin on the palms and soles. Focal palmoplantar keratoderma consists of localized areas of hyperkeratosis located mainly on pressure points and sites of recurrent friction. {ECO:0000269|PubMed:25285920}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Intolerance Scores

loftool: 0.192
rvis_EVS: 0.23
rvis_percentile_EVS: 68.58

Haploinsufficiency Scores

pHI: 0.252
hipred: N
hipred_score: 0.170
ghis: 0.518

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.356

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Trpv3
Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: response to heat;negative regulation of hair cycle;calcium ion transmembrane transport;positive regulation of calcium ion import
Cellular component: plasma membrane;integral component of plasma membrane;receptor complex
Molecular function: ion channel activity;calcium channel activity