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FLASH GENE
Symbol SMCHD1 contributors: mct - updated : 11-06-2019
HGNC name structural maintenance of chromosomes flexible hinge domain containing 1
HGNC id 29090
Corresponding disease
BAMS Bosma arhinia microphthalmia syndrome
FSHD2 Fascioscapulohumeral muscular dystrophy 2, digenic
Location 18p11.32      Physical location : 2.655.885 - 2.805.014
Genatlas name Structural Maintenance of Chromosomes Hinge Domain Containing 1
Synonym name
  • cDNA sequence,expressed in brain,98kDa
  • CDNA: FLJ21993 fis, clone HEP06576
  • SMCHD1 protein
  • SMC hinge domain-containing protein 1
  • Synonym symbol(s) KIAA0650, DKFZp686O0631, BAMS, FSHD2
    DNA
    TYPE functioning gene
    STRUCTURE 149.13 kb     45 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    45 - 8672 - 2005 - 2008 18425126
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C-terminal hinge domain of SMCHD1 forms a nucleic acid-binding homodimer
  • HOMOLOGY
    Homologene
    FAMILY SMC family
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,telomere
    basic FUNCTION
  • epigenetic modifier of gene expression that is critical to maintain X chromosome inactivation (Xi)
  • has an important role in CpG island (CGI) methylation on the inactive X chromosome (Xi) and in stable silencing of some Xi genes
  • epigenetic modifier essential for X chromosome inactivation
  • functions to control the expression of essential autosomal genes
  • has a role in the expression of several autosomal gene clusters that are subject to monoallelic expression, rather than being restricted to functioning uniquely in X inactivation
  • is an important regulator of imprinted and clustered genes )
  • important function of SMCHD1 in promoting non-homologous end joining (NHEJ) and repressing homologous recombination (HR) repair in response to DNA damage
  • plays an important role in epigenetic silencing at diverse loci, including the inactive X chromosome, imprinted genes, and the facioscapulohumeral muscular dystrophy locus
  • acts likely as a repressor on a limited set of autosomal gene clusters, as an observed reduction in methylation associates with a loss of SMCHD1 binding and increased expression for some of the loci
  • plays important roles in epigenetic silencing and normal mammalian development
  • is able to insulate chromatin, thereby limiting access to other chromatin-modifying proteins
  • is a key factor in defining the unique chromosome architecture of inactive X chromosome (Xi)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms an active GHKL-ATPase homodimer, contrasting with canonical SMC complexes, which exist as tripartite ring structures
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • heterochromatin protein 1 (HP1)-binding protein HBiX was required for SMCHD1 localization to H3K9me3 domains
  • is a chromatin repressor involved in the establishment and/or maintenance of CpG methylation at specific loci and binds directly to D4Z4
  • directly binds to D4Z4 and suppresses somatic expression of DUX4
  • is required for the dynamic methylation of the D4Z4 macrosatellite upon reprogramming but seems dispensable for methylation maintenance
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FSHD2 , BAMS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in many types of human hematopoietic malignancy
    constitutional germinal mutation      
    have also been reported as modifiers of disease severity in FSHMD1A-affected families with alleles of 810 D4Z4 units
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in mice, Smchd1 regulates chromatin repression at different loci, having a role in CpG methylation establishment and/or maintenance