Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Taking over the Atlas
Dear Colleagues,
The Atlas, once more, is in great danger, and I will have to proceed to a collective economic lay-off of all the team involved in the Atlas before the begining of April 2015 (a foundation having suddenly withdrawn its commitment to support the Atlas). I ask you herein if any Scientific Society (a Society of Cytogenetics, of Clinical Genetics, of Hematology, or a Cancer Society, or any other...), any University and/or Hospital, any Charity, or any database would be interested in taking over the Atlas, in whole or in part. If taking charge of the whole lot is too big, a consortium of various actors could be the solution (I am myself trying to find partners). Could you please spread the information, contact the relevant authorities, and find partners.
Survival of the Atlas will be critically dependant upon your ability to find solutions (and urgently!).
Kind regards.
Jean-Loup Huret
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TRPM1 (transient receptor potential cation channel, subfamily M, member 1)


Other namesLTRPC1
LocusID (NCBI) 4308
Location 15q13.3
Location_base_pair Starts at 31293264 and ends at 31453476 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note TRPM1, the founding member of TRPM family was originally identified as melastatin 1 and accordingly all 8 family members are named TRPM (melastatin) (Montell et al., 2002). TRPM1 expression is restricted to the pigment cells of skin and eye. The protein encoded by this gene is similar to that of transient receptor potential (TRP) calcium channel family members. The protein expression is inversely correlated with melanoma aggressiveness, suggesting a role in melanoma metastasis.


Description The TRPM1 gene consists of 27 exons, spans at least 58 kb genomic DNA, on chromosome 7 in mouse.
In humans, the chromosomal localization of TRPM1 is on chromosome 15q13.3 region from 29080845 to 29181216 on the reverse strand. The TRPM1 gene encodes a 5.4kb (5428bp) mRNA transcript (Hunter et al., 1998; Fang and Setaluri, 2000). The promoter region of this gene contains 4 consensus binding sites for the microphthalmia-associated transcription factor (MITF), one of those binding site includes an M box, a motif shared by pigmentation genes (Hunter et al., 1998; Miller et al., 2004; Zhiqi et al., 2004). A 1-kb PvuII fragment from this region is capable of driving reporter gene expression in mouse and human melanoma cells.
Transcription 5.4 kb mRNA (full length transcript) with open reading frame of 4.812 (NT 129 to NT 4940, GenBank Accession No. NM_002420). Northern hybridization studies showed the presence of multiple short transcripts (1.8kb, 4kb, and 5.4kb) in human melanocytes as well as pigmented metastatic melanoma cell lines. However the full length mRNA is detectable only in melanocytes. (Fang and Setaluri, 2000).
Pseudogene No pseudogenes for TRPM1 have been identified.


Note The open reading frame of TRPM1 (from NT 129-4940), encodes 1603 aa protein of predicted molecular mass ~182kDa. Cloning of full length human cDNA TRPM1 (GenBank Accession No. AF071787, with open reading frame from NT321- NT4922) resulted in 1533 aa protein product (Hunter et al., 1998; Fang and Setaluri, 2000). The shorter N-terminal isoform, TRPM1 (MLSN1-S), lacking the transmembrane domains, encodes for 500 aa protein (Fang and Setaluri, 2000). Rabbit polyclonal antibodies generated against the N-terminal part of TRPM1 detected proteins with molecular weights of 120 kDa and several minor bands ranging from 35 to 240kDa, including a doublet at 45kDa in primary neonatal melanocytes (Zhiqi et al., 2004).

Regulation of TRPM1: Short form of TRPM1 interacts directly and suppress the activity of full length form of TRPM1 (MLSN1-L), preventing its translocation to the plasma membrane (Xu et al., 2001), representing a mode of regulation of the channel activities. Presence of multiple isoforms of TRPM1 in normal melanocytes as well as pigment cell melanoma treated with a pharmacological agent suggests that TRPM1 can be regulated at the level of both transcription and mRNA processing (Fang and Setaluri, 2000). MITF is shown to be a major transcriptional regulator of TRPM1 expression through its interaction within the proximal promoter region (Miller et al., 2004; Zhiqi et al., 2004). Transfection of p53 or induction of endogenous p53 in melanocytes by ultraviolet (UV) radiation represses TRPM1 accompanied by decreased mobilization of intracellular Ca2+ and decreased extracellular Ca2+ uptake, indicating the role of p53 in TRPM1 regulation (Devi et al., 2007).

Description TRPM1 is alternatively spliced and the splice variants are strongly depending on the cell type. Northern blot and RT-PCR analysis showed that the alternative splicing of TRPM1 mRNA produces short TRPM1 mRNAs derived from the 5' or 3' ends of the full length TRPM1. One of the major isoforms is predicted to encode a short protein (MLSN1-S) that includes only the N-terminal segment but not any transmembrane domain and is incapable of functioning independently as an ion channel.
Expression TRPM1 is expressed exclusively in pigmented cells of the skin and the eyes.
Localisation Isoforms of TRPM1 is mostly likely located on plasma membrane. Of the two major isoforms of TRPM1, L form (MLSN1-L) is localized on the cell membrane and the S form (MLSN1-S) is localized in the cytoplasm (Xu et al., 2001).
Function TRPM1, transfected in heterologous HEK293T cells, acts as a calcium channel protein. The shorter isoform of TRPM1 has a regulatory effect on longer isoform, potentially suppresses the transport of longer isoform to cell membrane (Xu et al., 2001). Role of TRPM1 in cellular differentiation and proliferation was reported in human pigmented melanoma cell lines treated with hexamethylene bisacetamide (HMBA), were the expression of TRPM1 is upregulated (Fang and Setaluri, 2000). Lentiviral shRNA mediated knockdown of TRPM1 resulted in reduced intracellular Ca2+ and decreased Ca2+ uptake suggesting a role of TRPM1 in Ca2+ uptake by melanocytes (Devi et al., 2007).
Homology Sequence similarity analysis revealed a limited homology to TRP family of calcium channel proteins and ~45% identity within the first 1200 amino acids of C.elegans (Prawitt et al., 2000).


Note Several single nucleotide polymorphisms have been identified but none of them is shown to be associated with any disease.

Implicated in

Entity Melanoma
Note The exact role of TRPM1 in melanoma is not known.
Disease Homogeneous TRPM1 mRNA expression in primary cutaneous melanoma correlates with prolonged disease free survival, and with the progression of the tumor, the TRPM1 is diminished or completely abolished in metastatic melanoma (Duncan et al., 1998; Duncan et al., 2001; Deeds et al., 2000; Miller et al., 2004). Reduced expression of TRPM1 gene in the retina of homozygous appaloosa horses with CSNB (congenital stationary night blindness) and coat spotting patterns compared to non appaloosa horses suggests a role for TRPM1 in normal night vision and melanogenesis (Bellone et al., 2008).
Prognosis Down regulation/suppression of TRPM1 expression correlates with tumor progression. Decreased expression or absence of TRPM1 is a marker of poor prognosis and overall survival of melanoma patients.


Note No break points described so far.

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

HGNC (Hugo)TRPM1   7146
Entrez_Gene (NCBI)TRPM1  4308  transient receptor potential cation channel, subfamily M, member 1
GeneCards (Weizmann)TRPM1
Ensembl hg19 (Hinxton)ENSG00000134160 [Gene_View]  chr15:31293264-31453476 [Contig_View]  TRPM1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000134160 [Gene_View]  chr15:31293264-31453476 [Contig_View]  TRPM1 [Vega]
ICGC DataPortalENSG00000134160
Genatlas (Paris)TRPM1
SOURCE (Princeton)TRPM1
Genomic and cartography
GoldenPath hg19 (UCSC)TRPM1  -     chr15:31293264-31453476 -  15q13.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TRPM1  -     15q13.3   [Description]    (hg38-Dec_2013)
EnsemblTRPM1 - 15q13.3 [CytoView hg19]  TRPM1 - 15q13.3 [CytoView hg38]
Mapping of homologs : NCBITRPM1 [Mapview hg19]  TRPM1 [Mapview hg38]
OMIM603576   613216   
Gene and transcription
Genbank (Entrez)AB115498 AB115499 AB115500 AB115501 AB115502
RefSeq transcript (Entrez)NM_001252020 NM_001252024 NM_001252030 NM_002420
RefSeq genomic (Entrez)AC_000147 NC_000015 NC_018926 NG_016453 NT_010194 NT_187660 NW_001838206 NW_004929398
Consensus coding sequences : CCDS (NCBI)TRPM1
Cluster EST : UnigeneHs.732541 [ NCBI ]
CGAP (NCI)Hs.732541
Alternative Splicing : Fast-db (Paris)GSHG0010264
Alternative Splicing GalleryENSG00000134160
Gene ExpressionTRPM1 [ NCBI-GEO ]     TRPM1 [ SEEK ]   TRPM1 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ7Z4N2 (Uniprot)
NextProtQ7Z4N2  [Medical]
With graphics : InterProQ7Z4N2
Splice isoforms : SwissVarQ7Z4N2 (Swissvar)
Domains : Interpro (EBI)Ion_trans_dom   
Related proteins : CluSTrQ7Z4N2
Domain families : Pfam (Sanger)Ion_trans (PF00520)   
Domain families : Pfam (NCBI)pfam00520   
DMDM Disease mutations4308
Blocks (Seattle)Q7Z4N2
Human Protein AtlasENSG00000134160
Peptide AtlasQ7Z4N2
IPIIPI01009907   IPI00792283   IPI00889735   IPI00889562   IPI00385124   IPI00447329   IPI00871862   
Protein Interaction databases
IntAct (EBI)Q7Z4N2
Ontologies - Pathways
Ontology : AmiGOcalcium channel activity  plasma membrane  integral component of plasma membrane  transport  G-protein coupled glutamate receptor signaling pathway  visual perception  ion transmembrane transport  new growing cell tip  retinal rod cell development  transmembrane transport  calcium ion transport into cytosol  calcium ion transmembrane transport  cellular response to light stimulus  
Ontology : EGO-EBIcalcium channel activity  plasma membrane  integral component of plasma membrane  transport  G-protein coupled glutamate receptor signaling pathway  visual perception  ion transmembrane transport  new growing cell tip  retinal rod cell development  transmembrane transport  calcium ion transport into cytosol  calcium ion transmembrane transport  cellular response to light stimulus  
REACTOMEQ7Z4N2 [protein]
REACTOME PathwaysREACT_15518 Transmembrane transport of small molecules [pathway]
Protein Interaction DatabaseTRPM1
DoCM (Curated mutations)TRPM1
Wikipedia pathwaysTRPM1
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerTRPM1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TRPM1
Exome Variant ServerTRPM1
Genetic variants : HAPMAPTRPM1
Genomic Variants (DGV)TRPM1 [DGVbeta]
ICGC Data PortalENSG00000134160 
Somatic Mutations in Cancer : COSMICTRPM1 
CONAN: Copy Number AnalysisTRPM1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Eye diseases - LOVD
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
DECIPHER (Syndromes)15:31293264-31453476
Mutations and Diseases : HGMDTRPM1
OMIM603576    613216   
NextProtQ7Z4N2 [Medical]
Disease Genetic AssociationTRPM1
Huge Navigator TRPM1 [HugePedia]  TRPM1 [HugeCancerGEM]
snp3D : Map Gene to Disease4308
DGIdb (Drug Gene Interaction db)TRPM1
General knowledge
Homologs : HomoloGeneTRPM1
Homology/Alignments : Family Browser (UCSC)TRPM1
Phylogenetic Trees/Animal Genes : TreeFamTRPM1
Chemical/Protein Interactions : CTD4308
Chemical/Pharm GKB GenePA35496
Clinical trialTRPM1
Cancer Resource (Charite)ENSG00000134160
Other databases
PubMed32 Pubmed reference(s) in Entrez


Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis.
Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW.
Cancer Res. 1998 Apr 1;58(7):1515-20.
PMID 9537257
Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1).
Hunter JJ, Shao J, Smutko JS, Dussault BJ, Nagle DL, Woolf EA, Holmgren LM, Moore KJ, Shyjan AW.
Genomics. 1998 Nov 15;54(1):116-23.
PMID 9806836
Expression and Up-regulation of alternatively spliced transcripts of melastatin, a melanoma metastasis-related gene, in human melanoma cells.
Fang D, Setaluri V.
Biochem Biophys Res Commun. 2000 Dec 9;279(1):53-61.
PMID 11112417
Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression.
Prawitt D, Enklaar T, Klemm G, Gartner B, Spangenberg C, Winterpacht A, Higgins M, Pelletier J, Zabel B.
Hum Mol Genet. 2000 Jan 22;9(2):203-16.
PMID 10607831
Melastatin expression and prognosis in cutaneous malignant melanoma.
Duncan LM, Deeds J, Cronin FE, Donovan M, Sober AJ, Kauffman M, McCarthy JJ.
J Clin Oncol. 2001 Jan 15;19(2):568-76.
PMID 11208852
Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform.
Xu XZ, Moebius F, Gill DL, Montell C.
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10692-7. Epub 2001 Sep 4.
PMID 11535825
A unified nomenclature for the superfamily of TRP cation channels.
Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX.
Mol Cell. 2002 Feb;9(2):229-31.
PMID 11864597
Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma.
Miller AJ, Du J, Rowan S, Hershey CL, Widlund HR, Fisher DE.
Cancer Res. 2004 Jan 15;64(2):509-16.
PMID 14744763
Novel aspects of signaling and ion-homeostasis regulation in immunocytes. The TRPM ion channels and their potential role in modulating the immune response.
Perraud AL, Knowles HM, Schmitz C.
Mol Immunol. 2004 Jul;41(6-7):657-73. Review
PMID 15220002
Human melastatin 1 (TRPM1) is regulated by MITF and produces multiple polypeptide isoforms in melanocytes and melanoma.
Zhiqi S, Soltani MH, Bhat KM, Sangha N, Fang D, Hunter JJ, Setaluri V.
Melanoma Res. 2004 Dec;14(6):509-16.
PMID 15577322
Functional studies on the role of Melastatin 1/TRPM1 in human melanocytes.
Devi S, Kedlaya R, Maddodi N, Weber CS, Valdivia H, Setaluri V.
Pigment Cell Research. 20(4):331, August 2007.
Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus).
Bellone RR, Brooks SA, Sandmeyer L, Murphy BA, Forsyth G, Archer S, Bailey E, Grahn B.
Genetics. 2008 Aug;179(4):1861-70. Epub 2008 Jul 27.
PMID 18660533
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Written02-2009Sulochana Devi, Vijayasaradhi Setaluri
University of Wisconsin, School of Medicine and Public Health, Department of Dermatology, 439 Medical Science Centre, 1300 University Avenue, Madison, Wisconsin, 53706, USA


This paper should be referenced as such :
Devi, S ; Setaluri, V
TRPM1 (transient receptor potential cation channel, subfamily M, member 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):-.
Free journal version : [ pdf ]   [ DOI ]

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indexed on : Tue Feb 17 20:20:34 CET 2015

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