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FLASH GENE
Symbol ZHX2 contributors: mct/npt/pgu - updated : 12-07-2015
HGNC name zinc fingers and homeoboxes 2
HGNC id 18513
DNA
TYPE functioning gene
STRUCTURE 192.86 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 4516 - 837 - 2017 28258223
4 - 4373 92.2 837 - 2017 28258223
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Nervousbrainforebraincerebral cortex   Homo sapiensFetal
Urinarykidneynephronrenal capsuleglomerulus  Homo sapiens
Visualeyeretina    Mus musculus
cells
SystemCellPubmedSpeciesStageRna symbol
Urinarypodocyte Homo sapiens
Visualbipolar cell Mus musculusFetal
Visualcone photoreceptor Mus musculusAdult
VisualMuller cell Mus musculusAdult
cell lineage
cell lines
fluid/secretion blood
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two Cys(2)-His(2)-type zinc-finger motifs
  • five homeodomains (HDs)
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Zhx2
    homolog to murine Zhx2
    intraspecies paralog to ZHX1, ZHX3
    Homologene
    FAMILY
  • ZHX family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • having transcription factor activity
  • regulate podocyte gene expression during the development of nephrotic syndrome
  • ZHX2 contributes to AFP repression in the liver after birth and may also be involved in AFP reactivation in liver cancer
  • ZHX2 and ZHX3 were involved in the transcriptional repression of the hepatocellular cacinoma markers in normal hepatocytes, suggesting that the failure of the ZHX2 and/or ZHX3 expression might be a critical factor in the hepatocellular carcinogenesis
  • may participate in globin regulation and may be important in the normal physiology of erythrocytes
  • ZHX2 is a novel regulator of neural progenitor cell maintenance
  • acts as a transcriptional repressor in cell, and its repressor activity is enhanced by coexpression of an EFNB1 intracellular domain
  • functions as a novel developmental regulator of key genes influencing lipoprotein metabolism
  • ZHX2 promotes macrophage survival and proinflammatory functions in atherosclerotic lesions, thereby contributing to lesion growth
  • ZHX2 plays likely roles in the regulation of bipolar cell subset fate determination during retinal development
  • ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting MAPK14 signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • form homodimers but heterodimers with ZHX1
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • able to form a heterodimer with ZHX3 via a region containing each HD1(homeodomain)
  • binds to the cytoplasmic domain of EFNB1, which is expressed in cortical neural progenitors and plays a role in neural progenitor cell maintenance
  • ZHX2 suppresses GPC3 transcription by binding with its core promoter and reduced nucleic ZHX2 expression may be involved in GPC3 reactivation inhepatocellular carcinoma (HCC)
  • ZHX2 promoted NFKB1 activation
  • ZHX2 was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability
  • ZHX2 protects hepatocytes from abnormal lipid deposition in Non-alcoholic fatty liver disease (NAFLD) through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD-HCC progression
  • podocyte ZHX2 imbalance is a critical factor in glomerular disease, with minimal change disease disparities mediated mostly through ZHX1, and focal segmental glomerulosclerosis deviations through ZHX3 and ZHX2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    transcriptional deregulation of homeobox gene ZHX2 in Hodgkin lymphoma
    tumoral   translocation    
    aberration with recurrent breakpoints in Hodgkin lymphoma (HL), t(4;8)(q27;q24), which activate PDE5A and repress ZHX2, deregulating apoptosis, differentiation, and STAT1-signaling in HL cells
    tumoral     --low  
    in myeloma patients, compared with peripheral blood lymphocytes
    tumoral     --low  
    is responsible for GPC3 reactivation in hepatocellular carcinoma (HCC)
    tumoral     --over  
    in clear cell Renal cell carcinoma (RCC)
    tumoral     --over  
    high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    is a potential therapeutic target for Clear Cell Renal Cell Carcinoma (PMID: 30026228)
    ANIMAL & CELL MODELS
  • a mutation of Zhx2 carried in BALB/cJ mice is responsible in large part for its relative resistance to atherosclerosis