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Symbol ATRX contributors: mct - updated : 23-01-2019
HGNC name alpha thalassemia/mental retardation syndrome X-linked
HGNC id 886
Corresponding disease
ATRX alpha thalassemia / mental retardation syndrome, X-linked, non deletion type
CWS mental retardation-hypotonic facies syndrome
JMS Juberg-Marsidi syndrome
SFMS Smith-Fineman-Myers syndrome
Location Xq21.1      Physical location : 76.760.358 - 77.041.719
Synonym name
  • alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)
  • X-linked nuclear protein
  • X linked chromatin remodeling factor
  • DNA segment, single copy, probe FXNP1.111, 280kD
  • ATP-dependent helicase ATRX
  • transcriptional regulator ATRX
  • Synonym symbol(s) DXS6677E, SNF2L4, XH2, XNP, ATR2, MRXS3, RAD54, RAD54L, ZNF-HX, MRXHF1, SHS
    TYPE functioning gene
    STRUCTURE 281.36 kb     35 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - PGK1 PGK1 - ATRX ATRX - DXS56 - qter
    Physical map
    LOC347359 Xq13.1 similar to BMP-2 inducible protein kinase (BIKe) (HRIHFB2017) LOC392496 X similar to Rab coupling protein; Rab-interacting recycling protein; Rab effector protein; rab11-family interacting protein 1 LOC389874 X cellular nucleic acid binding protein-like LOC392497 X similar to 40S ribosomal protein S6 (Phosphoprotein NP33) LOC286493 Xq13.2 similar to Interferon-inducible, double stranded RNA dependent inhibitor, protein-kinase LOC392498 X similar to 40S ribosomal protein S7 (S8) SLC16A2 Xq13.2 solute carrier family 16 (monocarboxylic acid transporters), member 2 (putative transporter) PABPCP3 Xq13 poly(A) binding protein, cytoplasmic, pseudogene 3 RNF12 Xq13-q21 ring finger protein 12 KIAA2022 Xq13.2 KIAA2022 protein ABCB7 Xq13 ATP-binding cassette, sub-family B (MDR/TAP), member 7 MGC23937 Xq13.2 hypothetical protein MGC23937 similar to CG4798 LOC389875 X similar to telomeric repeat binding factor 1 isoform 2; Telomeric repeat binding factor 1; telomeric repeat binding protein 1 ZDHHC15 Xq13.1 zinc finger, DHHC domain containing 15 BRAF2 Xq13.2 similar to v-raf murine sarcoma viral oncogene homolog B1 pseudogene LOC286495 Xq13.2 similar to Tetratricopeptide repeat protein 3 (TPR repeat protein D) HCA3 Xq13.2 hepatocellular carcinoma-associated protein HCA3 MGC874 Xq13.2 hypothetical protein MGC874 LDHBP Xq13.2-q13.3 lactate dehydrogenase B pseudogene KIAA1587 Xq13.2 hepatocellular carcinoma-associated protein HCA1 LOC392499 X similar to hypothetical protein FLJ13611 ATRX Xq13.3 alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) DKFZp564K142 Xq13.3 implantation-associated protein COX7B Xq13.1 cytochrome c oxidase subunit VIIb ATP7A Xq13.3 ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome) PGK1 Xq13.3 phosphoglycerate kinase 1 TAF9L Xq13.1-q21.1 TAF9-like RNA polymerase II, TATA box binding protein (TBP)-associated factor, 31kDa CYSLTR1 Xq13-q21 cysteinyl leukotriene receptor 1 ZCCHC5 Xq13.3 zinc finger, CCHC domain containing 5 GPR23 Xq13-q21.1 G protein-coupled receptor 23 P2RY10 Xq21.1 purinergic receptor P2Y, G-protein coupled, 10 FKSG79 Xq13.3 putative purinergic receptor LOC347363 Xq13.3 similar to Chromosome-associated kinesin KIF4A (Chromokinesin) ITM2A Xq13.3-q21.2 integral membrane protein 2A TBX22 Xq21.1 T-box 22 MGC26999 Xq21.1 hypothetical protein MGC26999 LOC347364 Xq21.1 similar to WW domain binding protein 11; Npw38-binding protein NpwBP; SH3 domain-binding protein SNP70 LOC286425 Xq21.1 similar to hexokinase 2; hexokinase-2, muscle FLJ38568 Xq21.1 hypothetical protein FLJ38568
    TRANSCRIPTS type messenger
    text alternative splicing transcripts in the 5' region
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    35 - 11202 282.5 2492 - 2008 18409179
    exons 1 to 4
    34 splicing 11088 278 2454 widely 2008 18409179
    lacks exon 2 within the coding region (exons 1,3,4 )
    - splicing 10452 - 2288 brain, fibroblasts and kidney 2008 18409179
    an additional region leads to a translation frameshift, resulting in a N-terminal truncated protein (exons 2, 3, 4)
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Endocrineneuroendocrinepituitary  highly
    Hearing/Equilibriumear   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systembreastmammary gland highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • 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
    interspecies homolog to yeast SNF2/SWI2 (sucrase non fermenting)
    homolog to Drosophila brama (brm)
    homolog to murine Atrx
  • 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
  • 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
  • CELLULAR PROCESS nucleotide, chromatin organization, remodeling
    nucleotide, chromatin organization, methylation
    nucleotide, recombination
    nucleotide, repair
    nucleotide, transcription, regulation
    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)
    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 and MUS81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway
  • cell & other
    corresponding disease(s) ATRX , JMS , SFMS , CWS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • 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