ATRX

Gene Facts

• HGNC Symbol: ATRX (HGNC:886)
• HGNC Name: ATRX chromatin remodeler
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: RAD54, JMS, MRX52
• Alias symbols: XH2, XNP
• %HI: 6.65
• pLI: 1
• LOEUF: 0.12
• Cytoband: Xq21.1
• Genomic Coordinates:

  GRCh37/hg19:	chrX:76760358-77041702
  GRCh38/hg38:	chrX:77504880-77786216

• MANE Select Transcript: NM_000489.6 ENST00000373344.11
• 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... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-3220
• ClinGen Curation ID: CCID:006722
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Related Links:
  Request from external user.
• Last Evaluated: 07/31/2012

Haploinsufficiency (HI) Score Details

• HI Score: 3
• HI Evidence Strength: Sufficient Evidence for Haploinsufficiency

HI Disease

• alpha thalassemia-X-linked intellectual disability syndrome

HI Evidence

• PUBMED: PMID: 7697714
  In 2 unrelated patients with ATR-X syndrome, Gibbons et al. (1995) identified a 4635C-T transition in the ATRX gene, leading to premature termination of the polypeptide at codon 1528 (R1528X) and a 4641G-T transversion in the ATRX gene, resulting in a glu1530-to-ter (E1530X) substitution. An additional patient with ATR-X syndrome was found to have a 1973 basepair deletion in the ATRX gene.

• HI Evidence Comments: Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is and X-linked dominant disorder characterized by distinctive craniofacial features, genital anomalies, severe developmental delays, hypotonia, intellectual disability, and mild-to-moderate anemia secondary to alpha-thalassemia.

NOTE

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity

NOTE

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.