TRPM2

transient receptor potential cation channel subfamily M member 2, the group of Transient receptor potential cation channels|Nudix hydrolase family

Basic information

Region (hg38): 21:44350163-44443081

Previous symbols: [ "TRPC7" ]

Links

ENSG00000142185 ∙ NCBI:7226 ∙ OMIM:603749 ∙ HGNC:12339 ∙ Uniprot:O94759 ∙ 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 TRPM2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPM2 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				8	9	17
missense			115	21	12	148
nonsense			1	1	1	3
start loss						0
frameshift						0
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding				1	32	33
Total	0	0	116	32	55

Variants in TRPM2

This is a list of pathogenic ClinVar variants found in the TRPM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-44353843-G-T		not specified	Uncertain significance (Mar 02, 2023)
21-44353851-G-A		not specified	Uncertain significance (Dec 02, 2022)
21-44354664-C-T		not specified	Uncertain significance (Nov 21, 2022)
21-44364116-A-G		not specified	Uncertain significance (Mar 29, 2023)
21-44364140-C-A		not specified	Uncertain significance (Dec 22, 2023)
21-44364188-G-A		not specified	Uncertain significance (Jul 07, 2022)
21-44364207-G-A			Benign (Dec 31, 2019)
21-44364211-C-T		not specified	Uncertain significance (Aug 11, 2022)
21-44364252-C-T			Likely benign (Feb 25, 2018)
21-44364258-G-A			Benign (Dec 31, 2019)
21-44366485-G-G			Benign (Jun 19, 2021)
21-44366769-C-T			Uncertain significance (Feb 01, 2021)
21-44366785-G-A		not specified	Uncertain significance (Mar 21, 2023)
21-44366787-G-A			Likely benign (Dec 31, 2019)
21-44366826-G-A			Benign (Dec 31, 2019)
21-44366874-A-G		not specified	Uncertain significance (Jun 17, 2024)
21-44369179-G-T		not specified	Uncertain significance (Jan 03, 2024)
21-44369195-G-C		not specified	Uncertain significance (Jun 09, 2022)
21-44369273-G-T		not specified	Uncertain significance (Nov 30, 2022)
21-44369302-T-G		not specified	Uncertain significance (May 20, 2024)
21-44369320-C-A		not specified	Uncertain significance (Dec 20, 2023)
21-44369320-C-G		not specified	Uncertain significance (Mar 06, 2023)
21-44369351-C-A			Benign/Likely benign (Nov 01, 2022)
21-44375845-G-A		not specified	Uncertain significance (Sep 01, 2021)
21-44375899-AACC-A			Likely benign (Jun 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPM2	protein_coding	protein_coding	ENST00000397928	32	92919

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.96e-44	0.00000727	124953	3	792	125748	0.00317

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.335	988	959	1.03	0.0000646	9817
Missense in Polyphen		310	299.15	1.0363		3043
Synonymous	-3.29	516	429	1.20	0.0000326	2943
Loss of Function	0.720	70	76.8	0.911	0.00000370	827

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00617	0.00609
Ashkenazi Jewish	0.0113	0.0111
East Asian	0.00146	0.00141
Finnish	0.000562	0.000554
European (Non-Finnish)	0.00294	0.00287
Middle Eastern	0.00146	0.00141
South Asian	0.00403	0.00389
Other	0.00434	0.00424

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:27383051, PubMed:27068538). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (PubMed:19171771). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (By similarity). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (By similarity). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606). {ECO:0000250|UniProtKB:Q91YD4, ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:15561722, ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:19171771, ECO:0000269|PubMed:19454650, ECO:0000269|PubMed:20650899, ECO:0000269|PubMed:20660597, ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:25562606, ECO:0000269|PubMed:25918360, ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051, ECO:0000305}.; FUNCTION: Isoform 3: Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress. {ECO:0000269|PubMed:12594222}.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Ectoderm Differentiation;Neutrophil degranulation;Stimuli-sensing channels;Ion channel transport;Innate Immune System;Immune System;Transport of small molecules;Pentose phosphate pathway;TRP channels (Consensus)

Recessive Scores

• pRec: 0.0973

Intolerance Scores

• loftool: 0.797
• rvis_EVS: 1
• rvis_percentile_EVS: 90.56

Haploinsufficiency Scores

• pHI: 0.0958
• hipred: N
• hipred_score: 0.342
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.606

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trpm2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype

Gene ontology

• Biological process: temperature homeostasis;dendritic cell chemotaxis;calcium ion transport;response to purine-containing compound;calcium-mediated signaling using intracellular calcium source;sodium ion transmembrane transport;neutrophil degranulation;release of sequestered calcium ion into cytosol;regulation of filopodium assembly;cellular response to hydrogen peroxide;calcium ion transmembrane transport;cellular response to calcium ion;cellular response to purine-containing compound;cellular response to temperature stimulus;zinc ion transmembrane transport;dendritic cell differentiation;calcium ion transmembrane import into cytosol;calcium ion import across plasma membrane;regulation of actin cytoskeleton reorganization
• Cellular component: lysosome;lysosomal membrane;plasma membrane;integral component of plasma membrane;cytoplasmic vesicle membrane;specific granule membrane;cell projection;perikaryon;tertiary granule membrane;ficolin-1-rich granule membrane
• Molecular function: cation channel activity;calcium channel activity;sodium channel activity;calcium ion binding;calcium-release channel activity;hydrolase activity;ligand-gated calcium channel activity