TRPV1

protein-coding

transient receptor potential cation channel subfamily V member 1, the group of Transient receptor potential cation channels|Ankyrin repeat domain containing

Gene summary

Capsaicin, the main pungent ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The protein encoded by this gene is a receptor for capsaicin and is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. This receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo. Four transcript variants encoding the same protein, but with different 5' UTR sequence, have been described for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_080704.4

Inheritance

AD, AR

ClinVar variants

P:1U:144B:21

Top phenotype

Malignant hyperthermia of anesthesia

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr17:3,565,444-3,609,411

External References & Databases

Ensembl (ENSG00000196689)

Transcript & Mutation Effects

hg38 • Region Span ~44.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

malignant hyperthermia, susceptibility toMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0800188

Submitter: PanelApp Australia

channelopathy-associated congenital insensitivity to pain, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009459

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRPV1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 18

Malignant hyperthermia of anesthesiaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080704.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar	3 clinvar	10
missense		1 clinvar	139 clinvar	10 clinvar	2 clinvar	152
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	144	16	5	166

Highest pathogenic variant AF is 6.8425754e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080704.4	RefSeq	NP_542435.2	15	MANE Select
ENST00000572705.2	Ensembl	ENSP00000459962.1	15	MANE Select
NM_018727.5	RefSeq	NP_061197.4	15	Standard
NM_080705.4	RefSeq	NP_542436.2	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Serotonin and anxiety
Stimuli-sensing channels
Ion channel transport

Biological Process

negative regulation of transcription by RNA polymerase II
fever generation
microglial cell activation
diet induced thermogenesis
peptide secretion

Molecular Function

transmembrane signaling receptor activity
ion channel activity
extracellular ligand-gated ion channel activity
excitatory extracellular ligand-gated ion channel activity
calcium channel activity

Cellular Component

mitochondrion
cytosol
plasma membrane
integral component of plasma membrane
external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000571088
Coding exons: 15
Length: 31655
Individuals with no LoFs: 124996
Homozygous LoFs: 0
Heterozygous LoFs: 166
Defined: 125162
p: 0.000663

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.466	475	504	0.942	0.0000311	5421
Missense (PolyPhen)		167	176.58	0.94577		1848
Synonymous	-1.43	258	230	1.12	0.0000168	1626
Loss of Function	1.15	29	36.5	0.795	0.00000186	417

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0013	notable
Latino/Admixed American	0.00069	0.00064	rare
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.00064	0.00061	rare
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.00055	0.00054	rare
South Asian	0.00037	0.00036	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis. {ECO:0000250|UniProtKB:O35433, ECO:0000269|PubMed:11050376, ECO:0000269|PubMed:11226139, ECO:0000269|PubMed:11243859, ECO:0000269|PubMed:12077606}.;

Recessive Scores

pRec: 0.258

Intolerance Scores

RVIS EVS: 0.01
RVIS percentile EVS: 54.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low