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FLASH GENE
Symbol NSD2 contributors: mct/pgu - updated : 19-06-2023
HGNC name nuclear receptor binding SET domain protein 2
HGNC id 12766
Corresponding disease
WHS Wolf-Hirschhorn syndrome
WHSCR Wolf-Hirschhorn syndrome, mild form
Location 4p16.3      Physical location : -
Synonym name
  • multiple myeloma set domain
  • Wolf-Hirschhorn syndrome candidate 1
  • trithorax/ash1-related protein 5
  • IL5 promoter REII region-binding protein
  • Synonym symbol(s) MMSET, WHSC1, REIIBP, TRX5, FLJ23286, KIAA1090, MGC176638, REIIBP, KMT3F, KMT3G, RAUST, WHS
    EC.number 2.1.1.43/ 2.1.1.357
    DNA
    TYPE functioning gene
    STRUCTURE 110.81 kb     22 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map pter - TACC3 - FGFR3 - LETM1 - WHSC1 - WHSC2 - cen
    Authors Stec (01)
    RNA
    TRANSCRIPTS type messenger
    text complex alternative splicing and differential polyadenylation, complex transcription pattern, nine variants, five isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 7886 136 1365 - 2009 19121287
  • also called variant 1/isoform 1
  • lacking exon 12
  • - polyA site 5000-6000 62 647 widely 1998 9618163
  • short isoform
  • P exons 11a/b
  • - - - 64 667 - 1998 9618163
    exon 12+
    - - - - - - 1998 9618163
  • alternative splicing exons 2,3
  • some translation major product
  • 22 - 7589 - 1365 - 2009 19121287
    also called variant 10/isoform 1
    23 - 7706 136 1365 - 2009 19121287
  • also called variant 2/isoform 1
  • lacking exon 2
  • 22 - 7543 136 1365 - 2009 19121287
  • also called variant 3/isoform 1
  • lacking exon 2
  • - - 8460 62 802 - 2001 11152655
    additional fragment beyond exon 15, isoform 2 identical N-terminus than isoform 1, second ORF with identical C-terminus than isoform 1
    - - 8110 66 647 - 1998 9787135
    additional fragment beyond exon 11, lacking exons 12-25
    25 - 7980 66 647 - 1996 9787135
    full length transcript, truncated protein
    7 - 8390 66 647 - 2009 19121287
  • also called variant 7/isoform 3
  • terminating beyond exon 12
  • 11 - 5172 64 629 - 2009 19121287
  • also called variant 8/isoform 4
  • additional fragment beyond exon 11, shifting the ORF
  • 9 - 3620 60 584 - 2009 19121287
  • also called RE-IIB
  • lacking exons 1-10
  • (response element II-binding protein) translated from a second transcription initiation site
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text preferentially in rapidly growing tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a nuclear localization signal (NLS)
  • two PWWP (proline-2 tryptophan-proline)domains (one in N-terminus)
  • a HMG2 box, four PHD-type zinc fingers and a multifunctional chromatin regulator (130 AA) SET domain (Suvar, Enhancer of zest, Trithorax)
  • C-terminal SET domain characteristic of histone methyltransferases
  • HOMOLOGY
    interspecies homolog to Drosophila dysmorphy gene ash
    homolog to murine Whsc1l
    Homologene
    FAMILY
  • histone-lysine methyltransferase family
  • SET2 subfamily
  • nuclear receptor binding SET domain (NSD) protein family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • having ubiquitin-protein ligase activity
  • could be implicated in tumor emergence and/or progression
  • potentially acts as a pathogenic agent in many cancers
  • by acting directly as a modifier of chromatin as well as through binding of other chromatin modifying enzymes, may influence gene expression and potentially acts as a pathogenic agent in multiple myeloma
  • major regulator of chromatin structure and transcription in t(4;14) multiple myeloma cells
  • has a role in the DNA damage response
  • critical role of WHSC1 in regulating the assembly of TP53BP1 foci at DNA lesions
  • required for proliferation of neuroblastoma cells and brain-derived neural stem cells
  • critical in maintaining the chromatin integrity
  • dimethylation of histone H3 at lysine 36 (H3K36me2) is the principal chromatin-regulatory activity of WHSC1
  • EZH2 mediates histone H3K27 trimethylation and is associated with gene silencing, coordinately expressed and function upstream of WHSC1, which mediates H3K36 dimethylation and is associated with active transcription
  • critical role of NSD2-mediated H3K36 methylation in adipose tissue development and function
  • NSD2 is a critical epigenetic regulator for Follicular helper T (Tfh) differentiation
  • NSD2 plays a pivotal role in epigenomic maintenance and cell cycle control to prevent cellular senescence
  • NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis
  • NSD2 is a critical epigenetic regulator of Treg recruitment for maternal-fetal tolerance
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
  • pathway involving H2AFX–MDC1–WHSC1 regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates TP53BP1 recruitment
  • a component
  • component of transcription co-repressor complexes (HDAC1 and HDAC2, SIN3A and the histone demethylase AOF2)
  • EZH2-WHSC1 HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IL5 (suppression of transcription)
  • upstream regulator of TP53BP1
  • NSD2 catalyzes the methylation of histone H3 lysine 36 (H3K36)
  • SUPT6H recruitment is abrogated in cells lacking the histone methyltransferase NSD2
  • binding of NSD2 and NSD3 to mononucleosomes causes DNA near the linker region to unwrap, which facilitates insertion of the catalytic core between the histone octamer and the unwrapped segment of DNA
  • NSD2 is a key histone methyltransferase catalyzing histone H3 lysine 36 dimethylation (H3K36me2)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) WHS , WHSCR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused to IgH in multiple myeloma with translocation t(4;14)((p16.3;q32) with FGFR3 overexpression
    tumoral     --over  
    in multiple myeloma with poor prognosis, in patients with the translocation t(4;14)
    tumoral somatic mutation      
    in acute myeloid leukemia
    tumoral     --other  
    aberrant expression in glioblastoma multiform
    constitutional     --low  
    resulted in cellular hypersensitivity to ionizing radiation
    tumoral     --over  
    in neuroblastoma
    tumoral     --over  
    in both colon cancers and rectal cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene Wolf-Hirschhorn syndrome candidate gene 1
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    might be a strong candidate therapeutic target in a subset of neuroblastomas with unfavorable prognosis
    cancerhemopathy 
    is a promising target in hematological disorders
    cancerdigestivecolon
    promising therapeutic target in colorectal cancer
    ANIMAL & CELL MODELS