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

Gene ID: 140803, updated on 2-Nov-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
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Genomic context

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See TRPM6 in Genome Data Viewer
Location:
9q21.13
Exon count:
41
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (74722495..74887921, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (86875552..87041025, complement)
RS_2024_09 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 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. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) controls magnesium gatekeeper TRPM6 activity. Xie J, et al. Sci Rep, 2011. PMID 22180838, Free PMC Article
  2. [Novel type of signaling molecules: protein kinases covalently linked to ion channels]. Riazanova LV, et al. Mol Biol (Mosk), 2001 Mar-Apr. PMID 11357414
  3. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Walder RY, et al. Nat Genet, 2002 Jun. PMID 12032570
  4. Molecular determinants of permeation through the cation channel TRPM6. Topala CN, et al. Cell Calcium, 2007 Jun. PMID 17098283
  5. TRPM6: A Janus-like protein. Bödding M. Handb Exp Pharmacol, 2007. PMID 17217065

See all (69) 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
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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 calcium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables histone H2AS1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables magnesium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
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
  
Process Evidence Code Pubs
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 chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in magnesium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
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 protein 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 apical plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
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_2024_08

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

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