TRPM8

transient receptor potential cation channel subfamily M member 8, the group of Transient receptor potential cation channels

Basic information

Region (hg38): 2:233917372-234019522

Links

ENSG00000144481 ∙ NCBI:79054 ∙ OMIM:606678 ∙ HGNC:17961 ∙ Uniprot:Q7Z2W7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPM8 gene.

• Inborn genetic diseases (39 variants)
• not provided (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPM8 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	4	7
missense			39		3	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding					1	1
Total	0	0	39	3	8

Variants in TRPM8

This is a list of pathogenic ClinVar variants found in the TRPM8 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-233926549-G-A			Likely benign (Jun 15, 2018)
2-233926551-C-A		not specified	Uncertain significance (Jan 07, 2022)
2-233926602-G-A		not specified	Uncertain significance (Jan 17, 2023)
2-233926608-T-A		not specified	Uncertain significance (Apr 20, 2023)
2-233926619-G-A		not specified	Uncertain significance (Sep 12, 2023)
2-233930672-T-C		not specified	Uncertain significance (Jan 24, 2024)
2-233930676-G-T			Likely benign (May 25, 2018)
2-233937354-G-C		not specified	Uncertain significance (Mar 31, 2023)
2-233937462-G-A		not specified	Uncertain significance (Oct 26, 2021)
2-233937479-T-G		not specified	Uncertain significance (Jun 23, 2023)
2-233939030-A-C		not specified	Uncertain significance (Nov 09, 2021)
2-233939131-T-C		not specified	Uncertain significance (Sep 27, 2022)
2-233939143-T-C		not specified	Uncertain significance (Dec 22, 2023)
2-233939146-G-A		not specified	Uncertain significance (Feb 05, 2024)
2-233942621-A-G		not specified	Uncertain significance (Feb 21, 2024)
2-233942624-T-C		not specified	Uncertain significance (Jan 23, 2023)
2-233942704-A-C		not specified	Uncertain significance (Jan 02, 2024)
2-233942727-C-G			Benign (Jan 30, 2018)
2-233945896-G-C			Benign (Oct 17, 2019)
2-233945943-G-A		not specified	Uncertain significance (Jan 30, 2024)
2-233945976-G-A		not specified	Uncertain significance (Aug 02, 2023)
2-233945988-C-T		not specified	Uncertain significance (Dec 22, 2023)
2-233950012-G-A		not specified	Uncertain significance (Nov 07, 2022)
2-233950072-G-C		not specified	Uncertain significance (Apr 25, 2022)
2-233950085-G-A		not specified	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPM8	protein_coding	protein_coding	ENST00000324695	24	102124

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.60e-29	0.00682	125541	0	207	125748	0.000823

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.476	600	634	0.947	0.0000369	7324
Missense in Polyphen		174	208.47	0.83467		2412
Synonymous	-0.0455	260	259	1.00	0.0000163	2081
Loss of Function	1.29	50	60.9	0.821	0.00000340	670

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00226	0.00226
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000218	0.000217
Finnish	0.00190	0.00190
European (Non-Finnish)	0.000522	0.000519
Middle Eastern	0.000218	0.000217
South Asian	0.00159	0.00157
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration (PubMed:25559186). Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel. {ECO:0000269|PubMed:15306801, ECO:0000269|PubMed:16174775, ECO:0000269|PubMed:22128173, ECO:0000269|PubMed:25559186}.
• 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: 0.756
• rvis_EVS: -1.43
• rvis_percentile_EVS: 4.03

Haploinsufficiency Scores

• pHI: 0.0917
• hipred: Y
• hipred_score: 0.557
• ghis: 0.411

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.279

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trpm8
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: cellular calcium ion homeostasis;response to cold;detection of temperature stimulus;thermoception;protein homotetramerization;protein homotrimerization;calcium ion transmembrane transport;positive regulation of cold-induced thermogenesis
• Cellular component: endoplasmic reticulum membrane;plasma membrane;external side of plasma membrane;integral component of membrane;membrane raft
• Molecular function: calcium channel activity;protein binding;protein homodimerization activity