ClinGen Dosage Sensitivity Curation Page

SLC9A6

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
21812100 Takahashi (2011): One patient with X-linked mental retartdation and an Angelman syndrome-like phenotype was described with a frameshift mutation in exon 2. This mutations affects one of two variant transcripts, based on RT-PCR results, but Western blot showed no protein present. The mutation was inherited from a normal mother.
18342287 Gilfillan (2008): Described mutations in four families with X-linked mental retardation and Angelman-like phenotype. One family had a frameshift mutation found in affected males; 3 of 10 carrier females had some cognitive impairment. One family had a nonsense mutation in an affected male, inherited from a normal mother. The other two mutations were a 6-bp deletion and splice mutation.
19377476 Tarpey (2009): Report of two families with X-linked mental retardation, one with a frameshift mutation and one with a nonsense mutation that segregated with the phenotype. Carrier females were normal

Haploinsufficiency phenotype comments:

Additional mutations have been reported: PMID: 20949524, 20395263, 21932316.

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.