ATRX

Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. ATRX is required for deposition of the histone variant H3.3 at telomeres and other genomic repeats. These interactions are important for maintaining silencing at these sites.

In addition, ATRX undergoes cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis.

Inherited mutations of the ATRX gene are associated with an X-linked mental retardation (XLMR) syndrome most often accompanied by alpha-thalassemia (ATR-X) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. Female carriers may demonstrate skewed X chromosome inactivation.

Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours, gliomas, osteosarcomas, soft-tissue sarcomas, and malignant pheochromocytomas.{{cite journal|last1=Comino-Méndez|first1=I|title=ATRX driver mutation in a composite malignant pheochromocytoma|journal=Cancer Genetics|date=June 2016|volume=209 |issue=6|pages=272–7|doi=10.1016/j.cancergen.2016.04.058|pmid=27209355|hdl=10641/3656|hdl-access=free}} There is a strong correlation between ATRX mutations and an Alternative Lengthening of Telomeres (ALT){{Broken anchor|date=2025-05-23|bot=User:Cewbot/log/20201008/configuration|target_link=Telomere#ALT (Alternative Lengthening of Telomeres) and cancer|reason= The anchor (ALT (Alternative Lengthening of Telomeres) and cancer) has been deleted.|diff_id=829626327}} phenotype in cancers.

ATRX forms a complex with DAXX which is an histone H3.3 chaperone.

ATRX has been also shown to interact with EZH2.

• Alpha-thalassemia mental retardation syndrome

{{reflist|33em|refs =

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{{cite journal | vauthors = Voon HP, Hughes JR, Rode C, De La Rosa-Velázquez IA, Jenuwein T, Feil R, Higgs DR, Gibbons RJ | display-authors = 6 | title = ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes | journal = Cell Reports | volume = 11 | issue = 3 | pages = 405–18 | date = April 2015 | pmid = 25865896 | pmc = 4410944 | doi = 10.1016/j.celrep.2015.03.036 }}

{{cite journal | vauthors = Wong LH, McGhie JD, Sim M, Anderson MA, Ahn S, Hannan RD, George AJ, Morgan KA, Mann JR, Choo KH | display-authors = 6 | title = ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells | journal = Genome Research | volume = 20 | issue = 3 | pages = 351–60 | date = March 2010 | pmid = 20110566 | pmc = 2840985 | doi = 10.1101/gr.101477.109 }}

}}

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{{refend}}

• [https://www.ncbi.nlm.nih.gov/books/NBK1449/ GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia X-Linked Mental Retardation Syndrome; ATRX Syndrome; Alpha Thalassemia/Mental Retardation, X-Linked; XLMR-Hypotonic Face Syndrome]
• [https://www.ncbi.nlm.nih.gov/omim/300032,301040,300032,301040 OMIM entries on Alpha-Thalassemia X-Linked Mental Retardation Syndrome]
• {{UCSC gene info|ATRX}}
• {{UCSC gene info|RAD54L}}