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): 17:3510501-3557812

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.

• Isolated focal non-epidermolytic palmoplantar keratoderma (183 variants)
• not provided (151 variants)
• Olmsted syndrome 1 (30 variants)
• Inborn genetic diseases (23 variants)
• Isolated focal non-epidermolytic palmoplantar keratoderma;Olmsted syndrome 1 (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	19	19	41
missense	5	2	54	10	16	87
nonsense			2		1	3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1		1	2
splice region			2	5	4	11
non coding			54	8	108	170
Total	5	2	114	37	145

Highest pathogenic variant AF is 0.0000329

Variants in TRPV3

This is a list of pathogenic ClinVar variants found in the TRPV3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-3510577-G-C		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3510607-G-GCA		Olmsted syndrome 1	Uncertain significance (Jun 14, 2016)
17-3510610-C-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3510622-C-G		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3510659-C-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3510662-C-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3510721-A-G		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 12, 2018)
17-3510762-C-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Mar 20, 2018)
17-3510763-G-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 12, 2018)
17-3510768-A-G		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 12, 2018)
17-3510769-C-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3510803-G-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3510841-T-G		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3510866-T-C		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 12, 2018)
17-3510872-C-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3511022-G-C		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3511109-G-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3511133-C-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 12, 2018)
17-3511134-C-T		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3511157-T-G		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3511160-G-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3511188-T-C		Isolated focal non-epidermolytic palmoplantar keratoderma	Benign (Jan 13, 2018)
17-3511215-T-C		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3511246-G-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)
17-3511295-C-A		Isolated focal non-epidermolytic palmoplantar keratoderma	Uncertain significance (Jan 13, 2018)

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