ATRX
Protein-coding gene in humans
From Wikipedia, the free encyclopedia
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.[5][6][7]
Function
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.[8] These interactions are important for maintaining silencing at these sites.[9][10][11]
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.[7]
Clinical significance
Inherited mutations
Inherited mutations of the ATRX gene are associated with an X-linked intellectual disability (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.[7]
Somatic mutations
Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours,[12] gliomas,[13][14] osteosarcomas,[15] soft-tissue sarcomas,[16] and malignant pheochromocytomas.[17] There is a strong correlation between ATRX mutations and an Alternative Lengthening of Telomeres (ALT) phenotype in cancers.[12]