rs193922272

This is a variant in the GCK gene that changes a lysine to an glutamate.

ClinVar annotation

Pathogenic★★★★
9 submitters20 publications

GCK-related disorder; Maturity onset diabetes mellitus in young (MODY); Maturity-onset diabetes of the young type 2; Monogenic diabetes

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Research that mentions this SNP (1)

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia
ReviewKara K. Osbak et al.(2009)· Human Mutation

This is a comprehensive mutation review of the glucokinase (GCK) gene, documenting 620 mutations identified in 1,441 families that cause maturity-onset diabetes of the young (GCK-MODY), permanent neonatal diabetes mellitus (PNDM), and hyperinsulinemic hypoglycemia (GCK-HH). The paper reviews heterozygous inactivating GCK mutations causing mild fasting hyperglycemia in GCK-MODY, homozygous mutations causing severe PNDM, and activating mutations clustering in the allosteric activator site causing inappropriate insulin secretion. The GCK polymorphism rs4607517 is associated with increased fasting plasma glucose but not type 2 diabetes susceptibility.

Traits studied:Fasting plasma glucose levelsHyperinsulinemic hypoglycemia (GCK-HH)Maturity-onset diabetes of the young (GCK-MODY)Permanent neonatal diabetes mellitus (PNDM)

About GCK

This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]

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Gene information from NCBI Gene. Variant classifications from ClinVar.

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