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Symbol WHSC1 contributors: mct/pgu - updated : 18-02-2012
HGNC name Wolf-Hirschhorn syndrome candidate 1
HGNC id 12766
Corresponding disease
WHS Wolf-Hirschhorn syndrome
WHSCR Wolf-Hirschhorn syndrome, mild form
Location 4p16.3      Physical location : 1.873.122 - 1.983.933
Synonym name
  • multiple myeloma set domain
  • trithorax/ash1-related protein 5
  • IL5 promoter REII region-binding protein
  • Synonym symbol(s) MMSET, NSD2, REIIBP, TRX5, FLJ23286, KIAA1090, MGC176638, REIIBP
    TYPE functioning gene
    STRUCTURE 110.81 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - TACC3 - FGFR3 - LETM1 - WHSC1 - WHSC2 - cen
    Authors Stec (01)
    Physical map
    FLJ90036 4p16.3 hypothetical protein FLJ90036 LOC391611 4 similar to Zinc finger protein 208 ZNF141 4p16.3 zinc finger protein 141 (clone pHZ-44) FLJ14297 4p16.3 hypothetical protein FLJ14297 FLJ20265 4p16.3 hypothetical protein FLJ20265 PDE6B 4p16.3 phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant) ATP5I 4p16.3 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit e MYL5 4p16.3 myosin, light polypeptide 5, regulatory FLJ22269 4p16.3 hypothetical protein FLJ22269 RNF3 4p16.3 ring finger protein 3 CPLX1 4p16.3 complexin 1 GAK 4p16 cyclin G associated kinase MGC4618 4p16.3 hypothetical protein MGC4618 DGKQ 4p16.3 diacylglycerol kinase, theta 110kDa SLC26A1 4p16.3 solute carrier family 26 (sulfate transporter), member 1 IDUA 4p16.3 iduronidase, alpha-L- FGFRL1 4p16 fibroblast growth factor receptor-like 1 LOC285498 4p16.3 hypothetical protein LOC285498 LOC132969 4p16.3 similar to hornerin SPON2 4p16.3 spondin 2, extracellular matrix protein CTBP1 4p16 C-terminal binding protein 1 MGC21675 4p16.3 hypothetical protein MGC21675 MAEA 4p16.3 macrophage erythroblast attacher KIAA1530 4p16.3 KIAA1530 protein FLJ34443 4p16.3 hypothetical protein FLJ34443 HSPX153 4p16.3 HPX-153 homeobox LOC345375 4p16.3 similar to CG32656-PA LOC152877 4p16.3 similar to RIKEN cDNA 5430419M09 SLBP 4p16 stem-loop (histone) binding protein LOC92305 4p16.3 hypothetical protein BC009331 TACC3 4p16.3 transforming, acidic coiled-coil containing protein 3 FGFR3 4p16.3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) LETM1 4p16.3 leucine zipper-EF-hand containing transmembrane protein 1 WHSC1 4p16.3 Wolf-Hirschhorn syndrome candidate 1 WHSC2 4p16.3 Wolf-Hirschhorn syndrome candidate 2 LOC389195 4 hypothetical gene supported by BC038466; BC047038 FLJ37478 4p16.3 hypothetical protein FLJ37478 POLN 4p16.3 polymerase (DNA directed) nu MGC4701 4p16.3 hypothetical protein MGC4701 MXD4 4p16.3 MAX dimerization protein 4 KIAA1643 4p16.3 KIAA1643 protein LOC339985 4p16.3 hypothetical gene supported by BC010180 RNF4 4p16.3 ring finger protein 4 C4orf8 4p16.3 chromosome 4 open reading frame 8 TNIP2 4p16.3 TNFAIP3 interacting protein 2 LOC389196 4 LOC389196 SH3BP2 4p16.3 SH3-domain binding protein 2 ADD1 4p16.3 adducin 1 (alpha) TETRAN 4p16.3 tetracycline transporter-like protein C4orf9 4p16.3 chromosome 4 open reading frame 9 GPRK2L 4p16.3 G protein-coupled receptor kinase 2-like (Drosophila) HD 4p16.3 huntingtin (Huntington disease) LOC345222 4p16.3 hypothetical gene supported by BC043530 RGS12 4p16.3 regulator of G-protein signalling 12 HGFAC 4p16.3 HGF activator FLJ33718 4p16.3 hypothetical protein FLJ33718
    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
    Type ubiquitous
       expressed in (based on citations)
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    Text preferentially in rapidly growing tissues
  • 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
    interspecies homolog to Drosophila dysmorphy gene ash
    homolog to murine Whsc1l
  • histone-lysine methyltransferase family
  • SET2 subfamily
  • nuclear receptor binding SET domain (NSD) protein family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    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
  • CELLULAR PROCESS nucleotide, transcription
  • 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
    small molecule
  • IL5 (suppression of transcription)
  • upstream regulator of TP53BP1
  • cell & other
    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
    Variant & Polymorphism
    Candidate gene Wolf-Hirschhorn syndrome candidate gene 1
    Therapy target
    might be a strong candidate therapeutic target in a subset of neuroblastomas with unfavorable prognosis