Property Summary

NCBI Gene PubMed Count 48
PubMed Score 138.39
PubTator Score 87.41

Knowledge Summary

Patent (7,439)

TINX Plot

  Disease (5)

Expression

  Differential Expression (10)

Disease log2 FC p
osteosarcoma -3.351 3.2e-07
colon cancer -2.700 1.2e-07
ulcerative colitis -4.400 1.8e-07
group 3 medulloblastoma -1.200 7.6e-03
Endometriosis -3.186 4.8e-02
Pick disease -1.400 7.5e-04
progressive supranuclear palsy -1.300 2.8e-02
ovarian cancer 1.300 6.3e-12
head and neck cancer 1.300 6.8e-03
psoriasis 1.200 2.0e-37

Gene RIF (42)

PMID Text
26563869 Data show that resistant cells express lower amounts of the transient receptor potential cation channel subfamily M TRPM6 and 7, both involved in magnesium transport.
26179995 The Different Roles of The Channel-Kinases TRPM6 and TRPM7
26058915 we showed that two serum magnesium associated loci, MUC1 and TRPM6, had significant effect modification with progestin use and insulin levels, respectively, in European Americans.
25796343 TRPM6 mRNA and protein levels in atrial fibrillation group were elevated markedly in comparison with sinus rhythm group.
25277194 N-Myc can promote neuroblastoma cell proliferation through up-regulation of the channel kinases TRPM6 and TRPM7
24906182 Knowledge of TRPM6 functioning is of vital importance to decipher its role in Mg handling and will, in particular, provide a molecular basis for achieving a better understanding of Mg mal(re)absorption and hence systemic Mg balance.
24858416 Data indicate heteromer formation between channel kinases TRPM6 and TRPM7 influences the biological activity of the ion channels.
24650431 TRPM6 kinase activity is linked to channel activity through a kinase-independent mechanism involving the dimerization motif binding to a pocket within the kinase domain.
24385424 TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7.M6 channel complex.
23942199 We conclude that the new TRPM6 missense mutations lead to dysregulated intestinal/renal Mg(2+) (re)absorption as a consequence of loss of TRPM6 channel function.
23689795 Two novel mutations in Chinese sisters with familial hypomagnesemia with secondary hypocalcemia were found: one frameshift mutation (c.1196delC) and one non-sense mutation (c.4577G>A). Both patients were compound heterozygotes for these mutations.
22982920 Case Report: Resolving basal ganglia calcification in hereditary hypomagnesemia with secondary hypocalcemia due to a novel TRPM6 gene mutation.
22733750 Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy
22671428 Alteration in the expression and/or activity of magnesium channels is a frequent finding in cancer cells.
22180838 PIP2 is required for TRPM6 channel function; hydrolysis of PIP2 by PLC-coupled hormones/agonists may constitute an important pathway for TRPM6 gating, and perhaps Mg2+ homeostasis.
21669885 A novel mutation of TRPM6 gene is responsible for the development of familial hypommagnesaemia in Turkish children.
21073857 Results suggest that TRPM6 expression is up-regulated by a PI3K/Akt/mTOR pathway .
20875900 The present investigation further suggests that TRPM6 and TRPM7 gene variation may not be useful predictors for type 2 diabetes mellitus risk assessment.
20875900 Observational study of gene-disease association. (HuGE Navigator)
20700443 Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
20395377 Loss-of-function mutations cause hypomagnesemia with secondary hypocalcemia.
19937979 Up-regulation of TRPM6 transcriptional activity by AP-1 in renal epithelial cells.
19695239 Observational study of gene-disease association. (HuGE Navigator)
19329436 REA operates as a negative feedback modulator of TRPM6 in the regulation of active Mg(2+) (re)absorption and provides new insight into the molecular mechanism of renal transepithelial Mg(2+) transport.
19149903 Our results provide suggestive evidence that two common non-synonymous TRPM6 coding region variants, Ile1393Val and Lys1584Glu polymorphisms, might confer susceptibility to type 2 diabetes in women with low magnesium intake
19149903 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19073827 These findings clearly outline the activation of TRPM6 by EGF, a process fundamental to Mg2+ homeostasis.
18675813 TRPM6 and TRPM7 phosphorylate the assembly domain of myosin IIA, IIB and IIC on identical residues.
18660673 diverse molecular regulation of TRPM6 by magnesiotropic hormones, intracellular factors and its fused alpha-kinase domain disclosed novel regulatory mechanisms of active magnesium reabsorption--REVIEW
18490453 intracellular ATP regulates TRPM6 channel activity via its alpha-kinase domain independently of alpha-kinase activity
18365021 findings support a model where massive autophosphorylation outside the catalytic domain of TRPM6 and TRPM7 may facilitate kinase-substrate interactions leading to enhanced phosphorylation of those substrates
18301276 The predominant Mg transporters include TRPM6 and TRPM7
18192217 This review discusses the importance of magnesium in vascular biology and implications in hypertension and highlights the transport systems, particularly TRPM6--REVIEW
17217065 TRPM6 mutants are found in patients with a rare but severe hereditary disease called hypomagnesaemia with secondary hypocalcaemia --{REVIEW}
17098283 data demonstrate that amino acid residues E1024, I1030 and D1031 are important for channel function and that subtle amino acid variation in the pore region accounts for TRPM6 permeation properties
16636202 heterologous expression of TRPM6 but not the mutant TRPM6(S141L) produces functional channels with divalent cation permeability profile and pH sensitivity distinctive from those of TRPM7 channels and TRPM6/7 complexes
16150690 Although TRPM6 and TRPM7 are closely related and deficiency in either one of these molecules severely affects Mg(2+) homeostasis regulation, TRPM6 and TRPM7 do not appear to be functionally redundant.
16075242 In patients with primary hypomagnesaemia and secondary hypocalcaemia (HSH), a combined defect of intestinal magnesium absorption and renal magnesium conservation TRPM6 is the first component involved directly in epithelial magnesium reabsorption[review]
14976260 TRPM6 specifically interacted with its closest homolog, the Mg(2+)-permeable cation channel TRPM7, resulting in the assembly of functional TRPM6/TRPM7 complexes at the cell surface.
14576148 TRPM6 is specifically localized along the apical membrane of the renal distal convoluted tubule and the brush-border membrane of the small intestine and is specific for Mg2+ absoprtion.
12032570 Individuals with TRPM6 mutations have abnormal renal magnesium excretion. Deficiency causes hypomagnesemia with secondary hypocalcemia.
12032568 Deficiency /mutations of TRPM6 causes hypomagnesemia with secondary hypocalcemia

AA Sequence

MKEQPVLERLQSQKSWIKGVFDKRECSTIIPSSKNPHRCTPVCQVCQNLIRCYCGRLIGDHAGIDYSWTI      1 - 70
SAAKGKESEQWSVEKHTTKSPTDTFGTINFQDGEHTHHAKYIRTSYDTKLDHLLHLMLKEWKMELPKLVI     71 - 140
SVHGGIQNFTMPSKFKEIFSQGLVKAAETTGAWIITEGINTGVSKHVGDALKSHSSHSLRKIWTVGIPPW    141 - 210
GVIENQRDLIGKDVVCLYQTLDNPLSKLTTLNSMHSHFILSDDGTVGKYGNEMKLRRNLEKYLSLQKIHC    211 - 280
RSRQGVPVVGLVVEGGPNVILSVWETVKDKDPVVVCEGTGRAADLLAFTHKHLADEGMLRPQVKEEIICM    281 - 350
IQNTFNFSLKQSKHLFQILMECMVHRDCITIFDADSEEQQDLDLAILTALLKGTNLSASEQLNLAMAWDR    351 - 420
VDIAKKHILIYEQHWKPDALEQAMSDALVMDRVDFVKLLIEYGVNLHRFLTIPRLEELYNTKQGPTNTLL    421 - 490
HHLVQDVKQHTLLSGYRITLIDIGLVVEYLIGRAYRSNYTRKHFRALYNNLYRKYKHQRHSSGNRNESAE    491 - 560
STLHSQFIRTAQPYKFKEKSIVLHKSRKKSKEQNVSDDPESTGFLYPYNDLLVWAVLMKRQKMAMFFWQH    561 - 630
GEEATVKAVIACILYRAMAHEAKESHMVDDASEELKNYSKQFGQLALDLLEKAFKQNERMAMTLLTYELR    631 - 700
NWSNSTCLKLAVSGGLRPFVSHTCTQMLLTDMWMGRLKMRKNSWLKIIISIILPPTILTLEFKSKAEMSH    701 - 770
VPQSQDFQFMWYYSDQNASSSKESASVKEYDLERGHDEKLDENQHFGLESGHQHLPWTRKVYEFYSAPIV    771 - 840
KFWFYTMAYLAFLMLFTYTVLVEMQPQPSVQEWLVSIYIFTNAIEVVREICISEPGKFTQKVKVWISEYW    841 - 910
NLTETVAIGLFSAGFVLRWGDPPFHTAGRLIYCIDIIFWFSRLLDFFAVNQHAGPYVTMIAKMTANMFYI    911 - 980
VIIMAIVLLSFGVARKAILSPKEPPSWSLARDIVFEPYWMIYGEVYAGEIDVCSSQPSCPPGSFLTPFLQ    981 - 1050
AVYLFVQYIIMVNLLIAFFNNVYLDMESISNNLWKYNRYRYIMTYHEKPWLPPPLILLSHVGLLLRRLCC   1051 - 1120
HRAPHDQEEGDVGLKLYLSKEDLKKLHDFEEQCVEKYFHEKMEDVNCSCEERIRVTSERVTEMYFQLKEM   1121 - 1190
NEKVSFIKDSLLSLDSQVGHLQDLSALTVDTLKVLSAVDTLQEDEALLAKRKHSTCKKLPHSWSNVICAE   1191 - 1260
VLGSMEIAGEKKYQYYSMPSSLLRSLAGGRHPPRVQRGALLEITNSKREATNVRNDQERQETQSSIVVSG   1261 - 1330
VSPNRQAHSKYGQFLLVPSNLKRVPFSAETVLPLSRPSVPDVLATEQDIQTEVLVHLTGQTPVVSDWASV   1331 - 1400
DEPKEKHEPIAHLLDGQDKAEQVLPTLSCTPEPMTMSSPLSQAKIMQTGGGYVNWAFSEGDETGVFSIKK   1401 - 1470
KWQTCLPSTCDSDSSRSEQHQKQAQDSSLSDNSTRSAQSSECSEVGPWLQPNTSFWINPLRRYRPFARSH   1471 - 1540
SFRFHKEEKLMKICKIKNLSGSSEIGQGAWVKAKMLTKDRRLSKKKKNTQGLQVPIITVNACSQSDQLNP   1541 - 1610
EPGENSISEEEYSKNWFTVSKFSHTGVEPYIHQKMKTKEIGQCAIQISDYLKQSQEDLSKNSLWNSRSTN   1611 - 1680
LNRNSLLKSSIGVDKISASLKSPQEPHHHYSAIERNNLMRLSQTIPFTPVQLFAGEEITVYRLEESSPLN   1681 - 1750
LDKSMSSWSQRGRAAMIQVLSREEMDGGLRKAMRVVSTWSEDDILKPGQVFIVKSFLPEVVRTWHKIFQE   1751 - 1820
STVLHLCLREIQQQRAAQKLIYTFNQVKPQTIPYTPRFLEVFLIYCHSANQWLTIEKYMTGEFRKYNNNN   1821 - 1890
GDEITPTNTLEELMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKPEVKQSRGMVFGPANLGEDAIR   1891 - 1960
NFIAKHHCNSCCRKLKLPDLKRNDYSPERINSTFGLEIKIESAEEPPARETGRNSPEDDMQL           1961 - 2022
//

Text Mined References (49)

PMID Year Title
26563869 2015 Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin.
26179995 2015 The Different Roles of The Channel-Kinases TRPM6 and TRPM7.
26058915 2015 Genetic loci for serum magnesium among African-Americans and gene-environment interaction at MUC1 and TRPM6 in European-Americans: the Atherosclerosis Risk in Communities (ARIC) study.
25796343 2015 Increased TRPM6 expression in atrial fibrillation patients contribute to atrial fibrosis.
25277194 2014 N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation.
24906182 2014 Mg2+ homeostasis: the balancing act of TRPM6.
24858416 2014 TRPM6 kinase activity regulates TRPM7 trafficking and inhibits cellular growth under hypomagnesic conditions.
24650431 2014 Kinase and channel activity of TRPM6 are co-ordinated by a dimerization motif and pocket interaction.
24385424 2014 The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels.
23942199 2014 New TRPM6 missense mutations linked to hypomagnesemia with secondary hypocalcemia.
23689795 2013 Novel TRPM6 mutations in familial hypomagnesemia with secondary hypocalcemia.
22982920 2012 Resolving basal ganglia calcification in hereditary hypomagnesemia with secondary hypocalcemia due to a novel TRPM6 gene mutation.
22733750 2012 Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy.
22671428 2012 Magnesium and its transporters in cancer: a novel paradigm in tumour development.
22180838 2011 Phosphatidylinositol 4,5-bisphosphate (PIP(2)) controls magnesium gatekeeper TRPM6 activity.
21669885 2012 Clinical and molecular characterization of Turkish patients with familial hypomagnesaemia: novel mutations in TRPM6 and CLDN16 genes.
21073857 2011 Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells.
20875900 2010 Gene variation of the transient receptor potential cation channel, subfamily M, members 6 (TRPM6) and 7 (TRPM7), and type 2 diabetes mellitus: a case-control study.
20700443 2010 Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels.
20395377 2010 Renal TRPathies.
19937979 2010 Up-regulation of TRPM6 transcriptional activity by AP-1 in renal epithelial cells.
19695239 2009 Genetic determinants of extracellular magnesium concentration: analysis of multiple candidate genes, and evidence for association with the estrogen receptor alpha (ESR1) locus.
19329436 2009 Regulation of the epithelial Mg2+ channel TRPM6 by estrogen and the associated repressor protein of estrogen receptor activity (REA).
19149903 2009 Common genetic variants of the ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7), magnesium intake, and risk of type 2 diabetes in women.
19073827 2009 EGF increases TRPM6 activity and surface expression.
18675813 2008 The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin IIA, IIB and IIC.
18660673 2008 Insight into the molecular regulation of the epithelial magnesium channel TRPM6.
18490453 2008 Role of the alpha-kinase domain in transient receptor potential melastatin 6 channel and regulation by intracellular ATP.
18365021 2008 Massive autophosphorylation of the Ser/Thr-rich domain controls protein kinase activity of TRPM6 and TRPM7.
18301276 2008 Recent developments in intestinal magnesium absorption.
18258429 2008 RACK1 inhibits TRPM6 activity via phosphorylation of the fused alpha-kinase domain.
18192217 2008 Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17575980 2007 Differential expression of intestinal membrane transporters in cholera patients.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
17217065 2007 TRPM6: A Janus-like protein.
17098283 2007 Molecular determinants of permeation through the cation channel TRPM6.
16636202 2006 Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7.
16382100 2005 International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels.
16150690 2005 The channel kinases TRPM6 and TRPM7 are functionally nonredundant.
16075242 2005 Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis.
15164053 2004 DNA sequence and analysis of human chromosome 9.
14976260 2004 Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia.
14576148 2004 TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption.
12032568 2002 Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.
11357414 [Novel type of signaling molecules: protein kinases covalently linked to ion channels].
10021370 1999 Alpha-kinases: a new class of protein kinases with a novel catalytic domain.
9285786 1997 Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.