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

Summary

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

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_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Transcriptional Control of Trpm6 by the Nuclear Receptor FXR.
Title: Transcriptional Control of Trpm6 by the Nuclear Receptor FXR.
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.
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.
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].
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.
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.
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.
Spectrometric analysis identified phosphorylation sites in TRPM6 protein.
Title: Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases.
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.

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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	not available

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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:9484

D1S1423 (e-PCR)
- UniSTS:149619

FCA763 (e-PCR)
- UniSTS:265865

RH121555 (e-PCR)
- UniSTS:134296

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

EC 2.7.11.1

NP_001170782.1

EC 2.7.11.1

NP_060132.3

EC 2.7.11.1

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

NG_017036.1 RefSeqGene

Range

5174..170600

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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