Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

ATRX

contributors: mct - updated : 09-06-2021

HGNC name	alpha thalassemia/mental retardation syndrome X-linked
HGNC id	886

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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 blood / hematopoietic thymus       highly Endocrine neuroendocrine pituitary     highly Hearing/Equilibrium ear       highly Lymphoid/Immune lymph node       highly Reproductive female system breast mammary gland   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid         Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal containing a PHD type (C4-H-C3) zinc finger motif
	two functional nuclear localization signals
	two domains that target ATRX to nuclear speeckles
	a central region with ATPase helicase motifs homologous to RAD54
	ATRX-DNMT3-DNMT3L (ADD) domain, playing a role in normal pattern of DNA methylation with an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal -helix
	C terminal GLN rich domain with homology to SNF2, polyQ domain

HOMOLOGY

interspecies	homolog to yeast SNF2/SWI2 (sucrase non fermenting)
	homolog to Drosophila brama (brm)
	homolog to murine Atrx

Homologene

FAMILY	family of helicase/ATPase (SNF2/SWI2 family)
	SNF2/RAD54 helicase family

CATEGORY

DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
	intracellular,nucleus,nucleoplasm,nuclear bodies,PML
	intracellular,nucleus,chromatin/chromosome,euchromosome
	intracellular,nucleus,chromatin/chromosome,heterochromosome
	intracellular,nucleus,chromatin/chromosome,telomere
	intracellular,nucleus,chromatin/chromosome,centromere
text	associated with pericentromeric heterochromatin during interphase and mitosis
	associated with condensed chromatin at the onset of mitosis
	located at G-rich tandem repeats (TRs) in telomeres and euchromatin where it may recognize unusual DNA structures

basic FUNCTION	chromatin-remodeling protein, regulating gene expression via an effect on chromatin structure and/or function, at interphase and chromosomal segregation at mitosis
	helicase involved in DNA recombination and repair and transcription regulation, down-regulator of the alpha-globin locus, playing a role in the regulation of globin gene expression
	binding to the short arms of acrocentric chromosomes where the arrays of ribosomal DNA are located
	involved in DNA methylation, in brain development and facial morphogenesis
	may play an important role in transcription regulation, and involved in chromatin remodelling
	critical mediator of cell survival during early neuronal differentiation during and corticogenesis
	plays an important role in the recombinational repair of double-strand DNA (dsDNA) breaks
	play important roles during homologous recombination
	stimulates MUS81–EME1 endonuclease activity on various holliday junction-like intermediates (may cooperate in the processing of Holliday junction-like intermediates during homologous recombination or DNA repair)
	switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin
	contributes to chromosome dynamics during mitosis and provide a possible cellular explanation for reduced cortical size and abnormal brain development associated with ATRX deficiency
	transcriptional regulator, playing a novel function, working in conjunction with H3F3B, H3F3A and CBX5, as a key regulator of embryonic stem-cell telomere chromatin
	with DAXX are required for H3F3A deposition onto pericentric DNA repeats outside the S phase, and the DAXX/ATRX complex uses H3F3A to modulate the transcription from these repeats
	may be involved in recruitment of the complex DAXX/ATRX to telomeres
	essential for the maintenance of chromosome stability during female meiosis, and required to recruit the transcriptional regulator DAXX to pericentric heterochromatin at prophase I of meiosis
	chromatin-remodeling factor known to regulate DNA methylation at repetitive sequences of the human genome
	required for heterochromatin formation and maintenance of chromosome stability during meiosis
	required for centromere stability and the epigenetic control of heterochromatin function during meiosis and the transition to the first mitosis
	plays a critical role in the functional differentiation of chromatin structure during oogenesis and underscore the importance of chromatin remodeling proteins in the control of chromosome segregation during meiosis
	essential epigenetic component of pericentric heterochromatin for the repression of centromere mitotic rearrangements, DNA breaks and chromosome missegregation and hence as an important guardian of centromere integrity and function
	role of ATRX may be to recognize unusual forms of DNA and facilitate their resolution in several contexts
	required for the timely accumulation of the homologous recombination proteins RAD51 and BRCA2 at double-strand breaks
	important homologous recombination protein
	promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma
	chromatin remodeler that, together with its chaperone DAXX, deposits the histone variant H3.3 in pericentromeric and telomeric regions
	ATRX facilitates likely the chromatin reconstitution required for extended DNA repair synthesis and sister chromatid exchange during homologous recombination (HR)
	MECP2 and ATRX are reciprocally dependent both for their expression and targeting to chromocenters
	is likely required in excitatory neurons of the forebrain to achieve normal hippocampal long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the CA1 apical and basal dendritic synapses, respectively
	ATRX affects telomeric DSB repair by promoting cohesion of sister telomeres and that loss of ATRX in alternative lengthening of telomeres (ALT) cells results in diminished telomere cohesion

CELLULAR PROCESS	nucleotide, chromatin organization, remodeling
	nucleotide, chromatin organization, methylation
	nucleotide, recombination
	nucleotide, repair
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

chromatin-remodeling complex with DAXX, through their paired amphipathic alpha helices domains (ATP-dependent chromatin-remodeling complex, with ATRX being the core ATPase subunit and DAXX being the targeting subunit)

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	EZH2
	interacting with MECP2 (interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation)
	binds histone H3
	interacts with a DNA structure-specific endonuclease, MUS81–EME1 (might function together in the repair of damaged DNA)
	partner with cohesin and MECP2 and contributes to developmental silencing of imprinted genes in the brain
	interacts with H3F3A in maintaining telomere structural integrity in pluripotent embryonic stem cells)
	with DAXX are specifically associated with the H3F3A deposition machinery
	in euchromatin the predominant targets of ATRX are sequences containing VNTRs
	ATRX can directly enhance the expression of androgen-dependent genes through physical interaction with AR
	ATRX stimulates RAD51-mediated DNA strand exchange and promotes branch migration of Holliday junctions
	ATRX and MUS81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway
	at telomeres, DMRT2 competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability
	alternative lengthening of telomeres (ALT) activation is an adaptive response to ATRX/DAXX loss-induced telomere replication dysfunction
	ATRX has an effect on telomeric DSB repair and this role involves both telomere cohesion and a DAXX-dependent pathway
	the bromodomain of BRD9 binds acetylated K515 on ATRX and facilitates ATRX interaction with RAD51, which is essential for HR

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

ATRX , JMS , SFMS , CWS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional somatic mutation       in alpha-thalassemia myelodysplasia syndrome with poor prognosis, germinal mutations associated with besser prognosis tumoral fusion       with DAXX in promyelocytic leukemia (localization in nuclear bodies) constitutional     --low   results in the transmission of aneuploidy and the occurrence of centromeric breaks leading to a high incidence of structural and numerical chromosome aberrations in the pre-implantation embryo tumoral somatic mutation       in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX, in pancreatic neuroendocrine tumors constitutional       loss of function provokes progressive telomere decondensation that culminates in the inception of persistent telomere replication dysfunction

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	overexpression of ATRX in transgenic mice was associated with growth retardation, neural tube defects, and a high incidence of embryonic death, transgenic mice that survived to birth exhibited a high incidence of perinatal death as well as seizures, mild craniofacial anomalies, and abnormal behavior, in conclusion ATRX dosage is crucial for normal development and organization of the cortex
	loss of ATRX function during reproductive senescence may contribute to the onset of aneuploidy in the female gamete, and the reduced fertility observed in ATRX knockdown female mice underscores the importance of this model to determine the molecular mechanisms of aneuploidy and its effects on female fertility
	ScAtrxKO mice developed small testes and discontinuous tubules, due to prolonged G2/M phase and apoptosis of proliferating Sertoli cells during fetal life