ClinGen Dosage Sensitivity Curation Page

SLC38A5

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Froyen et al. (2007) describe three brothers with non-syndromic intellectual disability and a 50 kb deletion involving both the SLC38A5 and FTSJ1 genes (PMID: 17333282). The authors postulate that FTSJ1 is the gene responsible for the phenotype in these individuals, as mutations in this gene had previously been identified in others with X-linked syndromic intellectual disability. However, they remark that a role for SLC38A5 could not be definitively ruled out.

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

Triplosensitivity phenotype comment:

No duplications involving only SLC38A5 have been reported at this time. A large, 5 Mb duplication involving SLC38A5 in addition to many other genes, including other genes thought to be involved in X-linked nonsyndromic intellectual disability, has been reported (PMID:16900295).

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.