ClinGen Dosage Sensitivity Curation Page

SLC6A8

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11326334 Salomens (2001): First report of a patient with creatine transporter deficiency who had a nonsense mutation in SLC6A8. His mother and grandmother were carriers and had histories of learning disability.
16601897 Anselm (2006): Report of two patients with creatine transporter deficiency who had deletions of SLC6A8. Patient 1 had a de novo deletion of exons 8-13. Patient 2 had deletion of the entire gene, but the breakpoints were not well defined and the deletion may have included adjacent genes.
20717164 Betsalel (2011): Multiple patients reported with splicing, nonsense, and frameshift mutations. Introduction of LOVD mutation database.

Haploinsufficiency phenotype comments:

Loss of function mutations in SLC6A8 are responsible for creatine transport deficiency in males. Female carriers can be asymptomatic or may have milder phenotype including seizures and learning disabilities. See Gene Reviews.

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.