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TRPM2 transient receptor potential cation channel subfamily M member 2 [ Homo sapiens (human) ]

Gene ID: 7226, updated on 11-Apr-2024

Summary

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Official Symbol
TRPM2provided by HGNC
Official Full Name
transient receptor potential cation channel subfamily M member 2provided by HGNC
Primary source
HGNC:HGNC:12339
See related
Ensembl:ENSG00000142185 MIM:603749; AllianceGenome:HGNC:12339
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
KNP3; EREG1; TRPC7; LTRPC2; NUDT9H; LTrpC-2; NUDT9L1
Summary
The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]
Expression
Broad expression in bone marrow (RPKM 4.5), brain (RPKM 2.6) and 21 other tissues See more
Orthologs
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Genomic context

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Location:
21q22.3
Exon count:
35
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (44353621..44442644)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (42704215..42803115)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (45773504..45862527)

Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13379 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13380 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18568 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45724667-45725466 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45725506-45726160 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45726161-45726814 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45727470-45728123 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13381 Neighboring gene phosphofructokinase, liver type Neighboring gene Sharpr-MPRA regulatory region 3786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18569 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45751251-45751752 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45751753-45752252 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18570 Neighboring gene cilia and flagella associated protein 410 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr21:45761314-45761956 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr21:45761957-45762600 Neighboring gene NANOG hESC enhancer GRCh37_chr21:45763343-45763898 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45765021-45765523 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18572 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18571 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45790067-45790900 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45797213-45797712 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45797713-45798214 Neighboring gene ReSE screen-validated silencer GRCh37_chr21:45798708-45798913 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45821987-45822910 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:45825427-45826626 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18573 Neighboring gene TRPM2 antisense RNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45846369-45847280 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45847281-45848192 Neighboring gene Z6 small nucleolar RNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45857057-45857556 Neighboring gene Z6 small nucleolar RNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45861695-45862234 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45874390-45874890 Neighboring gene ReSE screen-validated silencer GRCh37_chr21:45875054-45875233 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13384 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45879794-45880676 Neighboring gene LRRC3 divergent transcript Neighboring gene leucine rich repeat containing 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. TRPM2-mediated Ca(2+) signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells. Ali ES, et al. Cell Commun Signal, 2023 Jun 19. PMID 37337283, Free PMC Article
  2. TRPM2 facilitates tumor progression of clear cell renal cell carcinoma by relieving Endoplasmic Reticulum Stress. Yuan H, et al. Int J Med Sci, 2023. PMID 36619219, Free PMC Article
  3. The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression. Bao L, et al. Sci Rep, 2022 Nov 29. PMID 36446940, Free PMC Article
  4. Sex-dependent effect of aging on calcium signaling and expression of TRPM2 and CRAC channels in human neutrophils. Vázquez-Prieto MLÁ, et al. Hum Immunol, 2022 Aug-Sep. PMID 35660323
  5. TRPM2 regulates autophagy to participate in hepatitis B virus replication. Chen L, et al. J Viral Hepat, 2022 Aug. PMID 35633088

See all (158) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Identification of Ligands for Ion Channels: TRPM2.
    Title: Identification of Ligands for Ion Channels: TRPM2.
  2. TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.
    Title: TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.
  3. TRPM2-L Participates in the Interleukin-6 Pathway to Enhance Tumor Growth in Prostate Cancer by Hypoxia-Inducible Factor-1alpha.
    Title: TRPM2-L Participates in the Interleukin-6 Pathway to Enhance Tumor Growth in Prostate Cancer by Hypoxia-Inducible Factor-1α.
  4. Endoplasmic Reticulum Stress-Related Ten-Biomarker Risk Classifier for Survival Evaluation in Epithelial Ovarian Cancer and TRPM2: A Potential Therapeutic Target of Ovarian Cancer.
    Title: Endoplasmic Reticulum Stress-Related Ten-Biomarker Risk Classifier for Survival Evaluation in Epithelial Ovarian Cancer and TRPM2: A Potential Therapeutic Target of Ovarian Cancer.
  5. Knockdown of TRPM2 promotes osteogenic differentiation of human periodontal ligament stem cells by modulating NF-kappaB /NLRP3 pathway.
    Title: Knockdown of TRPM2 promotes osteogenic differentiation of human periodontal ligament stem cells by modulating NF-κB /NLRP3 pathway.
  6. TRPM2-mediated Ca[2+] signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells.
    Title: TRPM2-mediated Ca(2+) signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells.
  7. TRPM2 facilitates tumor progression of clear cell renal cell carcinoma by relieving Endoplasmic Reticulum Stress.
    Title: TRPM2 facilitates tumor progression of clear cell renal cell carcinoma by relieving Endoplasmic Reticulum Stress.
  8. The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression.
    Title: The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression.
  9. Sex-dependent effect of aging on calcium signaling and expression of TRPM2 and CRAC channels in human neutrophils.
    Title: Sex-dependent effect of aging on calcium signaling and expression of TRPM2 and CRAC channels in human neutrophils.
  10. TRPM2 regulates autophagy to participate in hepatitis B virus replication.
    Title: TRPM2 regulates autophagy to participate in hepatitis B virus replication.
Submit: New GeneRIF Correction See all GeneRIFs (141)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC133383

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NOT enables ADP-ribose diphosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium channel activity TAS
Traceable Author Statement
more info
  
enables calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium ion binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
NOT enables hydrolase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables intracellularly gated calcium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables ligand-gated calcium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ligand-gated calcium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables manganese ion transmembrane transporter activity IEA
Inferred from Electronic Annotation
more info
  
enables mono-ADP-D-ribose binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables monoatomic cation channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables sodium channel activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in calcium ion import across plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in calcium ion transmembrane import into cytosol IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in calcium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in calcium ion transmembrane transport TAS
Traceable Author Statement
more info
  
involved_in calcium ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in calcium-mediated signaling using intracellular calcium source ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to calcium ion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to hydrogen peroxide IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to purine-containing compound ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to temperature stimulus ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in dendritic cell chemotaxis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in dendritic cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in manganese ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in protein homotetramerization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of actin cytoskeleton organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of filopodium assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in release of sequestered calcium ion into cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in release of sequestered calcium ion into cytosol IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in release of sequestered calcium ion into cytosol ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to heat IEA
Inferred from Electronic Annotation
more info
  
involved_in response to hydroperoxide IEA
Inferred from Electronic Annotation
more info
  
involved_in response to purine-containing compound IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sodium ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in temperature homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in zinc ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cell projection IEA
Inferred from Electronic Annotation
more info
  
located_in cytoplasmic vesicle membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in ficolin-1-rich granule membrane TAS
Traceable Author Statement
more info
  
located_in lysosomal membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in specific granule membrane TAS
Traceable Author Statement
more info
  
located_in tertiary granule membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
transient receptor potential cation channel subfamily M member 2
Names
estrogen-responsive element-associated gene 1 protein
long transient receptor potential channel 2
transient receptor potential channel 7
transient receptor potential melastatin 2
NP_001307279.2
NP_001307280.2
NP_001307281.1
NP_003298.2
XP_011528038.1
XP_016883946.1
XP_047296933.1
XP_047296934.1
XP_047296935.1
XP_054180807.1
XP_054180808.1
XP_054180809.1
XP_054180810.1
XP_054180811.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_022913.2 RefSeqGene

    Range
    5002..94025
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001320350.2 → NP_001307279.2  transient receptor potential cation channel subfamily M member 2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an additional in-frame exon in the 3' coding region, compared to variant 1, which results in a longer isoform (2), compared to isoform 1.
    Source sequence(s)
    AP001063, AP001064, AP001065
    Consensus CDS
    CCDS82681.1
    UniProtKB/TrEMBL
    E9PGK7, Q14DR2
    Related
    ENSP00000381026.2, ENST00000397932.6
    Conserved Domains (3) summary
    cd03670
    Location:1376 → 1549
    ADPRase_NUDT9; ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the Nudix hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also ...
    pfam00520
    Location:803 → 979
    Ion_trans; Ion transport protein
    cl39032
    Location:141 → 364
    LSDAT_euk; SLOG in TRPM

  2. NM_001320351.2 → NP_001307280.2  transient receptor potential cation channel subfamily M member 2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an in-frame exon in the 3' coding region, compared to variant 1, which results in a shorter isoform (3), compared to isoform 1.
    Source sequence(s)
    AP001063, AP001064, AP001065
    UniProtKB/TrEMBL
    Q14DR2
    Related
    ENSP00000300481.9, ENST00000300481.13
    Conserved Domains (3) summary
    cd03670
    Location:1292 → 1465
    ADPRase_NUDT9; ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the Nudix hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also ...
    pfam00520
    Location:803 → 979
    Ion_trans; Ion transport protein
    cl39032
    Location:141 → 364
    LSDAT_euk; SLOG in TRPM

  3. NM_001320352.3 → NP_001307281.1  transient receptor potential cation channel subfamily M member 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (4) with a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AP001065
    UniProtKB/TrEMBL
    B4DVI8
    Conserved Domains (1) summary
    cd03670
    Location:7 → 180
    ADPRase_NUDT9; ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the Nudix hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also ...

  4. NM_003307.4 → NP_003298.2  transient receptor potential cation channel subfamily M member 2 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AP001063, AP001064, AP001065
    Consensus CDS
    CCDS13710.1
    UniProtKB/Swiss-Prot
    D3DSL6, O94759, Q5KTC2, Q6J3P5, Q96KN6, Q96Q93
    UniProtKB/TrEMBL
    Q14DR2
    Related
    ENSP00000381023.1, ENST00000397928.6
    Conserved Domains (3) summary
    cd03670
    Location:1326 → 1499
    ADPRase_NUDT9; ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the Nudix hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also ...
    pfam00520
    Location:803 → 979
    Ion_trans; Ion transport protein
    cl39032
    Location:141 → 364
    LSDAT_euk; SLOG in TRPM

RNA

  1. NR_038257.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. This results in the introduction of a premature stop codon and renders the transcript a nonsense-mediated mRNA decay (NMD) candidate. Therefore, this transcript is not thought to be protein-coding.
    Source sequence(s)
    AP001063, AP001064, AP001065

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

    Range
    44353621..44442644
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011529736.3 → XP_011528038.1  transient receptor potential cation channel subfamily M member 2 isoform X1

    UniProtKB/TrEMBL
    Q14DR2
    Conserved Domains (2) summary
    cd03670
    Location:1356 → 1529
    ADPRase_NUDT9; ADP-ribose pyrophosphatase (ADPRase) catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. Like other members of the Nudix hydrolase superfamily of enzymes, it is thought to require a divalent cation, such as Mg2+, for its activity. It also ...
    pfam00520
    Location:810 → 979
    Ion_trans; Ion transport protein

  2. XM_017028457.3 → XP_016883946.1  transient receptor potential cation channel subfamily M member 2 isoform X2

    UniProtKB/TrEMBL
    Q14DR2

  3. XM_047440977.1 → XP_047296933.1  transient receptor potential cation channel subfamily M member 2 isoform X3

  4. XM_047440978.1 → XP_047296934.1  transient receptor potential cation channel subfamily M member 2 isoform X4

  5. XM_047440979.1 → XP_047296935.1  transient receptor potential cation channel subfamily M member 2 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060945.1 Alternate T2T-CHM13v2.0

    Range
    42704215..42803115
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054324832.1 → XP_054180807.1  transient receptor potential cation channel subfamily M member 2 isoform X6

  2. XM_054324833.1 → XP_054180808.1  transient receptor potential cation channel subfamily M member 2 isoform X2

  3. XM_054324834.1 → XP_054180809.1  transient receptor potential cation channel subfamily M member 2 isoform X3

  4. XM_054324835.1 → XP_054180810.1  transient receptor potential cation channel subfamily M member 2 isoform X4

  5. XM_054324836.1 → XP_054180811.1  transient receptor potential cation channel subfamily M member 2 isoform X5

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001001188.3: Suppressed sequence

    Description
    NM_001001188.3: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O94759.2 GenPept UniProtKB/Swiss-Prot:O94759

Gene LinkOut

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