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    TRPM6 transient receptor potential cation channel subfamily M member 6 [ Homo sapiens (human) ]

    Gene ID: 140803, updated on 11-Apr-2024

    Summary

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    Official Symbol
    TRPM6provided by HGNC
    Official Full Name
    transient receptor potential cation channel subfamily M member 6provided by HGNC
    Primary source
    HGNC:HGNC:17995
    See related
    Ensembl:ENSG00000119121 MIM:607009; AllianceGenome:HGNC:17995
    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
    HSH; HMGX; HOMG; CHAK2; HOMG1
    Summary
    This gene is predominantly expressed in the kidney and colon, and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis, and plays an essential role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Mutations in this gene are associated with hypomagnesemia with secondary hypocalcemia. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Apr 2010]
    Expression
    Biased expression in colon (RPKM 8.1), small intestine (RPKM 3.5) and 5 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    9q21.13
    Exon count:
    41
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (74722495..74887921, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (86875552..87041025, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (77337411..77502837, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr9:77093507-77093676 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:77111887-77112099 Neighboring gene Sharpr-MPRA regulatory region 6114 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:77114153-77114929 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:77114988-77115488 Neighboring gene RORB antisense RNA 1 Neighboring gene RAR related orphan receptor B Neighboring gene uncharacterized LOC105376088 Neighboring gene Sharpr-MPRA regulatory region 9792 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28467 Neighboring gene RN7SK pseudogene 47 Neighboring gene ribosomal protein SA pseudogene 75 Neighboring gene Sharpr-MPRA regulatory region 9148 Neighboring gene NANOG hESC enhancer GRCh37_chr9:77490497-77490998 Neighboring gene RNA, U6 small nuclear 445, pseudogene Neighboring gene RNY4 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 214 Neighboring gene required for meiotic nuclear division 1 homolog (S. cerevisiae) pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28468 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19951 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19952 Neighboring gene chromosome 9 open reading frame 40

    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. TRPM6 N-Terminal CaM- and S100A1-Binding Domains. Zouharova M, et al. Int J Mol Sci, 2019 Sep 9. PMID 31505788, Free PMC Article
    2. [Analysis of TRPM6 gene variant in a pedigree affected with hypocalcemia secondary to hypomagnesemia]. Tan J, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2019 Aug 10. PMID 31400133
    3. Increased risk of post-stroke epilepsy in Chinese patients with a TRPM6 polymorphism. Fu CY, et al. Neurol Res, 2019 Apr. PMID 30739590
    4. Exome sequencing identifies a novel frameshift variant causing hypomagnesemia with secondary hypocalcemia. Azim MK, et al. CEN Case Rep, 2019 Feb. PMID 30144020, Free PMC Article
    5. Histone phosphorylation by TRPM6's cleaved kinase attenuates adjacent arginine methylation to regulate gene expression. Krapivinsky G, et al. Proc Natl Acad Sci U S A, 2017 Aug 22. PMID 28784805, Free PMC Article

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Magnesium Status, Genetic Variants of Magnesium-Related Ion Channel Transient Receptor Potential Membrane Melastatin 6 (TRPM6) and the Risk of Gestational Diabetes Mellitus in Chinese Pregnant Women: A Nested Case-Control Study.
      Title: Magnesium Status, Genetic Variants of Magnesium-Related Ion Channel Transient Receptor Potential Membrane Melastatin 6 (TRPM6) and the Risk of Gestational Diabetes Mellitus in Chinese Pregnant Women: A Nested Case-Control Study.
    2. Transcriptional Control of Trpm6 by the Nuclear Receptor FXR.
      Title: Transcriptional Control of Trpm6 by the Nuclear Receptor FXR.
    3. Evidence for the expression of TRPM6 and TRPM7 in cardiomyocytes from all four chamber walls of the human heart.
      Title: Evidence for the expression of TRPM6 and TRPM7 in cardiomyocytes from all four chamber walls of the human heart.
    4. data unambiguously confirm that CaM and S100A1 share the same binding domain at the TRPM6 N-terminus although the ligand-binding mechanism is different.
      Title: TRPM6 N-Terminal CaM- and S100A1-Binding Domains.
    5. The homozygous c.3311C>T (p.Pro1104Leu) variant of the TRPM6 gene probably underlies hypocalcemia secondary to hypomagnesemia in this pedigree.
      Title: [Analysis of TRPM6 gene variant in a pedigree affected with hypocalcemia secondary to hypomagnesemia].
    6. Exome sequencing identifies a novel frameshift variant in TRPM6 causing hypomagnesemia with secondary hypocalcemia.
      Title: Exome sequencing identifies a novel frameshift variant causing hypomagnesemia with secondary hypocalcemia.
    7. The TRPM6 rs2274924 polymorphism may be associated with susceptibility to epilepsy following stroke, and the C allele may be associated with increased risk of post-stroke epilepsy.
      Title: Increased risk of post-stroke epilepsy in Chinese patients with a TRPM6 polymorphism.
    8. Results identified high expression of TRPM6 to be indicative of a prolonged overall survival in colorectal patients. Computational analysis suggest that TRPM6 may be targeted by hsalet7g and hsalet7f1.
      Title: Identification of key tumorigenesis‑related genes and their microRNAs in colon cancer.
    9. Spectrometric analysis identified phosphorylation sites in TRPM6 protein.
      Title: Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases.
    10. These findings confirm that TRPM6 cannot be replaced by TRPM7, and that TRPM6/7 complexes and TRPM6/7-mediated Mg(2+) influx are indispensable in human epithelial colon cells.
      Title: TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon.
    Submit: New GeneRIF Correction See all GeneRIFs (55)

    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

    Associated conditions

    Description Tests
    Intestinal hypomagnesemia 1
    MedGen: C1865974 OMIM: 602014 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels.
    EBI GWAS Catalog

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium channel activity TAS
    Traceable Author Statement
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables monoatomic cation channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in calcium ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in metal ion transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in monoatomic cation transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein tetramerization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to toxic substance IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in apical plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in brush border membrane 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 TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    transient receptor potential cation channel subfamily M member 6
    Names
    channel kinase 2
    melastatin-related TRP cation channel 6
    NP_001170781.1
    NP_001170782.1
    NP_060132.3

    NCBI Reference Sequences (RefSeq)

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    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_017036.1 RefSeqGene

      Range
      5174..170600
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001177310.2 → NP_001170781.1  transient receptor potential cation channel subfamily M member 6 isoform b

      See identical proteins and their annotated locations for NP_001170781.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) contains an alternate 5' terminal exon compared to variant a. This results in a shorter isoform (b) with a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AF350881, AL354795, AY333283
      Consensus CDS
      CCDS55319.1
      UniProtKB/Swiss-Prot
      Q9BX84
      Related
      ENSP00000396672.2, ENST00000449912.6
      Conserved Domains (3) summary
      smart00811
      Location:1749 → 1967
      Alpha_kinase; Alpha-kinase family
      pfam00520
      Location:848 → 1068
      Ion_trans; Ion transport protein
      pfam16519
      Location:1169 → 1220
      TRPM_tetra; Tetramerization domain of TRPM

    2. NM_001177311.2 → NP_001170782.1  transient receptor potential cation channel subfamily M member 6 isoform c

      See identical proteins and their annotated locations for NP_001170782.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (c) contains an alternate 5' terminal exon compared to variant a. This results in a shorter isoform (c) with a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AF350881, AL354795, AY333284
      Consensus CDS
      CCDS55318.1
      UniProtKB/Swiss-Prot
      Q9BX84
      Related
      ENSP00000354962.3, ENST00000361255.7
      Conserved Domains (3) summary
      smart00811
      Location:1749 → 1967
      Alpha_kinase; Alpha-kinase family
      pfam00520
      Location:848 → 1068
      Ion_trans; Ion transport protein
      pfam16519
      Location:1169 → 1220
      TRPM_tetra; Tetramerization domain of TRPM

    3. NM_017662.5 → NP_060132.3  transient receptor potential cation channel subfamily M member 6 isoform a

      See identical proteins and their annotated locations for NP_060132.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) encodes the longest isoform (a).
      Source sequence(s)
      AF350881, AL354795
      Consensus CDS
      CCDS6647.1
      UniProtKB/Swiss-Prot
      Q6VPR8, Q6VPR9, Q6VPS0, Q6VPS1, Q6VPS2, Q9BX84
      Related
      ENSP00000354006.1, ENST00000360774.6
      Conserved Domains (3) summary
      smart00811
      Location:1754 → 1972
      Alpha_kinase; Alpha-kinase family
      pfam00520
      Location:853 → 1073
      Ion_trans; Ion transport protein
      pfam16519
      Location:1174 → 1225
      TRPM_tetra; Tetramerization domain of TRPM

    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_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      74722495..74887921 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      86875552..87041025 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BX84.2 GenPept UniProtKB/Swiss-Prot:Q9BX84

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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