protein
Transcriptional regulator ATRX
Gene
ATRX
Organism
Homo sapiens(9606)
Length
2492 aa
Mass
282,587 Da
# ATRX Protein Summary
ATRX (transcriptional regulator ATRX) is a chromatin remodeling protein of 2,492 amino acids that functions as the catalytic component of the ATRX:DAXX complex (UniProt: P46100). It possesses ATP-dependent DNA translocase activity and facilitates transcriptional regulation through remodeling of chromatin structure, particularly at repetitive DNA elements. ATRX binds DNA tandem repeats including telomeric sequences and G-quadruplex structures, and mediates replication-independent deposition of histone H3.3 at pericentric repeats and telomeres.
ATRX is involved in maintaining telomere integrity, regulating imprinted gene expression at the IGF2/H19 locus, and controlling chromatin states of zinc-finger genes through interaction with TRIM28 and SETDB1 (UniProt: P46100). Loss-of-function mutations in ATRX cause multiple X-linked disorders including alpha-thalassemia/impaired intellectual development syndrome (ATRX), intellectual disability-hypotonic facies syndrome (MRXHF1), and alpha-thalassemia myelodysplasia syndrome (ATMDS).
ATRX is classified as a syndromic autism-related gene (SFARI Cat S), indicating that pathogenic ATRX variants are associated with autism spectrum disorder within the context of broader syndromic presentations involving intellectual disability and developmental delay.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610)
Disease associations
Alpha-thalassemia/impaired intellectual development syndrome, X-linkedATRX
A disorder characterized by severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.
Intellectual disability-hypotonic facies syndrome, X-linked, 1MRXHF1
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSHF1 features include severe intellectual disability, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.
Alpha-thalassemia myelodysplasia syndromeATMDS
A disorder characterized by hypochromic, microcytic red blood cells, hemoglobin H detected in peripheral blood, and multilineage myelodysplasia.
Sources
Last updated 5/6/2026, 5:24:34 AM