ClinGen Dosage Sensitivity Curation Page

AR

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22334387 Gottlieb et al. (2012) provide an update on the mutational spectrum of AR based on the current AR variant database. This database includes over 500 AR variants in androgen insensitivity syndrome (AIS) patients, including 54 premature stop codons and 21 partial gene deletions.
27994190 Saranya et al. (2016) identified three novel AR mutations, including two LOF variants p.Q68X and p D266fs295ter, associated with androgen insensitivity syndrome in sex-reversed XY female patients.
30742848 Liu et al. (2019) identified a de novo LOF variant (c.192_193insTAGCAG, p.Gln65*) in a patient with severe forms of complete androgen insensitivity syndrome.

Haploinsufficiency phenotype comments:

Loss of function variants in the AR gene have been associated with androgen insensitivity syndrome (AIS). A different condition, spinal and bulbar muscular atrophy of Kennedy, is caused by CAG repeat expansion in the AR gene.

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.