ClinGen Dosage Sensitivity Curation Page

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ATRX

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
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.

Haploinsufficiency phenotype 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.

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 score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

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.