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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	149.13 kb     45 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015295 45 - 8672 NP_056110 - 2005 - 2008 18425126

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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 8–10 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