Property Summary

NCBI Gene PubMed Count 63
PubMed Score 250.66
PubTator Score 99.00

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Expression

  Differential Expression (26)

Disease log2 FC p
malignant mesothelioma 1.600 1.9e-07
ependymoma -1.600 5.0e-10
osteosarcoma -2.254 4.3e-05
glioblastoma -1.900 1.6e-06
medulloblastoma 2.300 1.8e-08
atypical teratoid / rhabdoid tumor 2.000 2.0e-08
medulloblastoma, large-cell 2.100 3.6e-06
primitive neuroectodermal tumor 2.200 7.4e-06
Atopic dermatitis 1.400 2.5e-06
adrenocortical carcinoma 1.224 1.9e-03
pancreatic ductal adenocarcinoma liver m... 1.160 3.5e-02
non-small cell lung cancer 1.449 9.6e-22
intraductal papillary-mucinous carcinoma... 1.200 1.2e-03
intraductal papillary-mucinous neoplasm ... 1.600 2.6e-02
lung cancer 1.900 1.3e-02
pediatric high grade glioma 1.500 7.3e-06
pilocytic astrocytoma -1.500 3.9e-07
subependymal giant cell astrocytoma -1.838 5.0e-03
lung adenocarcinoma 1.700 2.4e-12
Breast cancer 1.700 5.9e-26
breast carcinoma 1.200 5.1e-30
gastric carcinoma 1.500 2.8e-02
ductal carcinoma in situ 1.200 2.5e-04
invasive ductal carcinoma 1.600 4.8e-04
ovarian cancer 1.200 1.2e-03
pituitary cancer 1.300 2.1e-04

MLP Assay (3)

AID Type Active / Inconclusive / Inactive Description
743445 screening 1662 / 0 / 308170 Development of Small Molecule Probes of the Histone Methyltransferase, NSD2 Measured in Biochemical System Using Plate Reader - 7053-01_Inhibitor_SinglePoint_HTS_Activity_Set2
743459 summary 0 / 0 / 0 Broad Institute Development of Small Molecule Probes of the Histone Methyltransferase, NSD2 Inhibitor Probe Project
1053173 confirmatory 390 / 3 / 1110 Development of Small Molecule Probes of the Histone Methyltransferase, NSD2 Measured in Biochemical System Using Plate Reader - 7053-01_Inhibitor_Dose_CherryPick_Activity

Gene RIF (42)

PMID Text
26912663 results identify a pivotal role for NSD2 binding to its catalytic product in regulating its cellular functions, and suggest a model for how this interaction may facilitate epigenetic spreading and propagation of H3K36me2.
26787850 NSD2 preferentially catalyzes the dimethylation of H3K36 along with a reduced preference for H3K36 monomethylation
26771714 In MMSET-depleted cells there are defects in DNA replication and a decreased association with chromatin.
26206755 It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20.
25942451 Studies indicate that the NSD methyltransferases NSD1, NSD2/WHSC1/MMSET and NSD3/WHSC1L1 were overexpressed, amplified or somatically mutated in multiple types of cancer, suggesting their critical role in cancer.
25494638 The results describe the binding of NSD1, 2 and 3 catalytic domains (CD) on histone tails through recognition of histone-lysine and methylation properties.
25280969 Results show that WHSC1 is overexpressed in Squamous cell carcinoma of the head and neck (SCCHN) and that it promotes cell-cycle progression through activation of NEK7, indicating its potential role as an oncogenic force in SCCHN.
24923560 The role of the shorter isoform (REIIBP) in myeloma cells was characterized and identified a clear and novel interaction of REIIBP with members of the SMN complex.
24809779 Gastric cancer patients with high MMSET and BRCA1 attain a longer median survival compared with those with high BRCA1 and low MMSET.
24019522 all of the H3K36-specific methyltransferases, including ASH1L, HYPB, NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A.
23963300 Haploinsufficiency of WHSC1 and/or LETM1 contributes to Wolf-Hirschhorn Syndrome, but that loss of distinct and/or additional genes in 4p16.3 is necessary for the expression of the core Wolf-Hirschhorn Syndrome phenotype.
23900284 In this study it was found MMSET knockdown could reduce SLAMF7 levels in t(4;14) MM cells. Furthermore, we found MMSET proteins were enriched in the SLAMF7 promoter region and regulated the transcription level of SLAMF7.
23823660 it will be of interest to determine whether inhibition of MMSET activity can be beneficial not only for t(4;14)thorn MM patients but also for patients who express a mutant allele of this protein.
23566000 High MMSET expression correlated with the advanced extent of serous ovarian carcinoma and poor outcome.
23241889 MMSET, a gene often deleted in Wolf-Hirschhorn syndrome, regulates class switch recombination provides one possible mechanism for Ab deficiency observed in these patients.
23225158 Overexpression of MMSET was significantly associated with Edmondson stage.
23159737 The EZH2-MMSET-histone methylase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis.
22972034 Overexpression of the histone methyltransferase MMSET is associated with myeloma.
22797064 Depletion of TWIST1 in MMSET-overexpressing cells blocked cell invasion and epithelial-mesenchymal transition, indicating that TWIST1 is a critical target of MMSET, responsible for the acquisition of an invasive phenotype.
22751105 ACA11, an orphan box H/ACA class small nucleolar RNA (snoRNA) encoded within an intron of WHSC1, was highly expressed in t(4;14)-positive multiple myeloma and other cancers
22645312 NSD2 is a key chromatin regulator of NF-kappaB and mediator of the cytokine autocrine loop for constitutive NF-kappaB activation and emphasize the important roles played by NSD2 in cancer cell proliferation and survival and tumor growth.
22099308 NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming.
22028615 Data show significant up-regulation of WHSC1 expression in bladder and lung cancer cells at both transcriptional and the protein levels.
21788515 WHSC1 regulates the methylation status of the histone H4 K20 residue and is required for the recruitment of 53BP1 to sites of DNA damage.
21527557 MMSET is implicated in neuroblastomagenesis possibly by supporting proliferation of progenitor cells and negatively regulating their differentiation.
21385930 The histone methyltransferase and putative oncoprotein MMSET is overexpressed in a large variety of human tumors.
21293379 a pathway involving gammaH2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates 53BP1 recruitment
20974671 overexpression of multiple myeloma SET domain protein is associated with the translocation t(4;14)in multiple myeloma.
20634891 Observational study of gene-disease association. (HuGE Navigator)
19481544 NSD2 protein is recruited to the enhancer region of the PSA gene by AR in an agonist-enhanced manner.
19121287 These data suggest that MMSET potentially acts as a pathogenic agent in many cancers.
19059936 dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival
18182627 WHSC1 expression increases with ascending tumor proliferation activity.
18172012 RE-IIBP is upregulated in leukemia. SET domain Cys483 & Arg477 are needed for histone methyltransferase activity. Overexpression causes histone H3-K27 methylation, HDAC recruitment, & histone H3 hypoacetylation on the IL-5 promoter repressing expression.
18156491 MMSET influences gene expression and potentially acts as a pathogenic agent in multiple myeloma
18036184 MM Patients showing the t(4;14) chromosomal translocation at FGFR3 and MMSET genes had a significant elevation of serum crosslaps, reported to be the marker most reliably correlated with the extent of bone resorption
17942756 that MMSET plays a significant role in t(4;14) MM and suggest that therapies targeting this gene could impact this particular subset of poor-prognosis patients.
17239852 Our results suggest that HMTase WHISTLE induces apoptosis in an HMTase activity-dependent manner and represses transcription of target genes through HDAC1 recruitment.
16682010 Overexpression of WHISTLE repressed transcription of the SV40 promoter. Our results suggest that WHISTLE is a novel SET domain containing a protein with specific H3K4 and H3K27 HMTase activity.
15677557 different transcripts detected, multiple myeloma SET domain containing protein (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein (RE-IIBP), are produced by alternative splicing
12715353 connection between the syndrome phenotype and cytogenetic abnormalities, through gradual shortening of the length of the critical region WHSCR (finally up to 165 kb), and sequencing it, at least 2 genes (WHSC1 and WHSC2) were identified.
12433679 data indicate that t(4;14)(p16;q32) and loss of fibroblast growth factor receptor 3 occurred at a very early stage of multiple myeloma and suggest that activation of multiple myeloma SET domain protein may be transforming event of this translocation

AA Sequence

MEFSIKQSPLSVQSVVKCIKMKQAPEILGSANGKTPSCEVNRECSVFLSKAQLSSSLQEGVMQKFNGHDA      1 - 70
LPFIPADKLKDLTSRVFNGEPGAHDAKLRFESQEMKGIGTPPNTTPIKNGSPEIKLKITKTYMNGKPLFE     71 - 140
SSICGDSAADVSQSEENGQKPENKARRNRKRSIKYDSLLEQGLVEAALVSKISSPSDKKIPAKKESCPNT    141 - 210
GRDKDHLLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDAPERAWIFEKS    211 - 280
LVAFEGEGQFEKLCQESAKQAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFLYVG    281 - 350
DQLHLNPQVAKEAGIAAESLGEMAESSGVSEEAAENPKSVREECIPMKRRRRAKLCSSAETLESHPDIGK    351 - 420
STPQKTAEADPRRGVGSPPGRKKTTVSMPRSRKGDAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQ    421 - 490
WSLLSEKQRARYNTKFALVAPVQAEEDSGNVNGKKRNHTKRIQDPTEDAEAEDTPRKRLRTDKHSLRKRD    491 - 560
TITDKTARTSSYKAMEAASSLKSQAATKNLSDACKPLKKRNRASTAASSALGFSKSSSPSASLTENEVSD    561 - 630
SPGDEPSESPYESADETQTEVSVSSKKSERGVTAKKEYVCQLCEKPGSLLLCEGPCCGAFHLACLGLSRR    631 - 700
PEGRFTCSECASGIHSCFVCKESKTDVKRCVVTQCGKFYHEACVKKYPLTVFESRGFRCPLHSCVSCHAS    701 - 770
NPSNPRPSKGKMMRCVRCPVAYHSGDACLAAGCSVIASNSIICTAHFTARKGKRHHAHVNVSWCFVCSKG    771 - 840
GSLLCCESCPAAFHPDCLNIEMPDGSWFCNDCRAGKKLHFQDIIWVKLGNYRWWPAEVCHPKNVPPNIQK    841 - 910
MKHEIGEFPVFFFGSKDYYWTHQARVFPYMEGDRGSRYQGVRGIGRVFKNALQEAEARFREIKLQREARE    911 - 980
TQESERKPPPYKHIKVNKPYGKVQIYTADISEIPKCNCKPTDENPCGFDSECLNRMLMFECHPQVCPAGE    981 - 1050
FCQNQCFTKRQYPETKIIKTDGKGWGLVAKRDIRKGEFVNEYVGELIDEEECMARIKHAHENDITHFYML   1051 - 1120
TIDKDRIIDAGPKGNYSRFMNHSCQPNCETLKWTVNGDTRVGLFAVCDIPAGTELTFNYNLDCLGNEKTV   1121 - 1190
CRCGASNCSGFLGDRPKTSTTLSSEEKGKKTKKKTRRRRAKGEGKRQSEDECFRCGDGGQLVLCDRKFCT   1191 - 1260
KAYHLSCLGLGKRPFGKWECPWHHCDVCGKPSTSFCHLCPNSFCKEHQDGTAFSCTPDGRSYCCEHDLGA   1261 - 1330
ASVRSTKTEKPPPEPGKPKGKRRRRRGWRRVTEGK                                      1331 - 1365
//

Text Mined References (70)

PMID Year Title
26912663 2016 A PWWP Domain of Histone-Lysine N-Methyltransferase NSD2 Binds to Dimethylated Lys-36 of Histone H3 and Regulates NSD2 Function at Chromatin.
26787850 2016 Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36.
26771714 2016 MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.
26206755 2015 RE-IIBP Methylates H3K79 and Induces MEIS1-mediated Apoptosis via H2BK120 Ubiquitination by RNF20.
25942451 2015 The NSD family of protein methyltransferases in human cancer.
25494638 2014 In vitro histone lysine methylation by NSD1, NSD2/MMSET/WHSC1 and NSD3/WHSC1L.
25280969 2015 WHSC1 promotes oncogenesis through regulation of NIMA-related kinase-7 in squamous cell carcinoma of the head and neck.
24923560 2014 A novel functional role for MMSET in RNA processing based on the link between the REIIBP isoform and its interaction with the SMN complex.
24809779 2014 Differential effect of MMSET mRNA levels on survival to first-line FOLFOX and second-line docetaxel in gastric cancer.
24129315 2014 Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.
24019522 2013 Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases.
23963300 2014 Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf-Hirschhorn Syndrome.
23900284 2013 Plasma membrane proteomics identifies biomarkers associated with MMSET overexpression in T(4;14) multiple myeloma.
23823660 2014 Point mutation E1099K in MMSET/NSD2 enhances its methyltranferase activity and leads to altered global chromatin methylation in lymphoid malignancies.
23566000 2013 Overexpression of multiple myeloma SET domain (MMSET) is associated with advanced tumor aggressiveness and poor prognosis in serous ovarian carcinoma.
23241889 2013 The histone methyltransferase MMSET regulates class switch recombination.
23225158 2013 Overexpression of MMSET is correlation with poor prognosis in hepatocellular carcinoma.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23159737 2013 Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer.
22972034 2013 MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c-MYC.
22797064 2013 The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial-mesenchymal transition and invasive properties of prostate cancer.
22751105 2012 Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress.
22645312 2012 Histone methyltransferase NSD2/MMSET mediates constitutive NF-?B signaling for cancer cell proliferation, survival, and tumor growth via a feed-forward loop.
22099308 2011 NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming.
22028615 2011 Histone lysine methyltransferase Wolf-Hirschhorn syndrome candidate 1 is involved in human carcinogenesis through regulation of the Wnt pathway.
21788515 2011 Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage.
21527557 2011 MMSET is highly expressed and associated with aggressiveness in neuroblastoma.
21385930 2011 The histone methyltransferase and putative oncoprotein MMSET is overexpressed in a large variety of human tumors.
21293379 2011 MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites.
20974671 2011 The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells.
20634891 2010 Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19481544 2009 The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19121287 2009 MMSET is overexpressed in cancers: link with tumor aggressiveness.
19059936 2009 MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18182627 2008 Identification of a novel proliferation-related protein, WHSC1 4a, in human gliomas.
18172012 2008 Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity.
18156491 2008 The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor.
18036184 2008 Evaluation of bone disease in multiple myeloma patients carrying the t(4;14) chromosomal translocation.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17942756 2008 The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity.
17719568 2007 Subtractive hybridisation screen identifies genes regulated by glucose deprivation in human neuroblastoma cells.
17239852 2007 The histone methyltransferase activity of WHISTLE is important for the induction of apoptosis and HDAC1-mediated transcriptional repression.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16682010 2006 Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity.
16197452 2005 Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma.
16115125 2005 Identification of ID-1 as a potential target gene of MMSET in multiple myeloma.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15734578 2005 The etiology of Wolf-Hirschhorn syndrome.
15677557 2005 Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15257719 2004 Identification of a novel IGH-MMSET fusion transcript in a human myeloma cell line with the t(4;14)(p16.3;q32) chromosomal translocation.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12715353 2002 [Genetic determination of Wolf-Hirschhorn syndrome ].
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12433679 2003 A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript.
11337357 2001 Translocation T(4;14)(p16.3;q32) is a recurrent genetic lesion in primary amyloidosis.
11252005 2001 First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation.
11152655 2001 A unique mRNA initiated within a middle intron of WHSC1/MMSET encodes a DNA binding protein that suppresses human IL-5 transcription.
10945609 2000 Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by reverse transcription-polymerase chain reaction analysis of IGH-MMSET fusion transcripts.
10470851 1999 Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
9787135 1998 The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts.
9618163 1998 WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.
9354676 1997 A novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene.
9207791 1997 Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.
9063753 1997 A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.