ClinGen Dosage Sensitivity Curation Page

GK

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
8651297 Walker et al. (1996) report mutations in GK in 3 families with isolated GK deficiency. Pt 1 had no GK activity, but was in good health. A splice site mutation resulting in a premature stop codon was identified. Pts 2 & 3 were brothers with a deletion of exon 17. Pt 2 had a more severe phenotype, including growth and psychomotor retardation delay, bone dysplasia, and seizures, while Pt 3 had normal development. Pt 4 had ID and a missense mutation was identified (D440V).
9719371 Sjarif et al. (1998) report mutations in GK in 3 families with isolated GK deficiency. The phenotypes varied greatly among the probands, though all had GK deficiency. The reported mutations included a 20 kb deletion near the 3' end of the gene, a nonsense mutation (R413X), and a missense change (W503R).
10851254 Sargent et al. (2000) report 5 mutations in GK in patients with isolated GK deficiency, including two nonsense changes (R310X and Q403X).

Haploinsufficiency phenotype comments:

Loss of function mutations (missense and nonsense) in the GK gene have been associated with isolated glycerol kinase deficiency (MIM: 300474), an X-linked recessive disorder that is marked by a wide phenotypic spectrum. Isolated GKD can be either symptomatic with episodic metabolic and CNS decompensation or asymptomatic with hyperglycerolemia and glyceroluria only (PMIDs 11479736, 12855219, 10851254). Complex glycerol kinase deficiency is caused by a contiguous deletion involving the GK gene and flanking genes DAX1, the gene associated with adrenal hypoplasia congenita, and DMD, the Duchenne muscular dystrophy gene (MIM:300679).

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:

Duplications involving the GK gene have not been reported.

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.