rs1057524900

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

ClinVar annotation

Pathogenic★★★★
5 submitters10 publications

Microcephaly, normal intelligence and immunodeficiency (NBS); Monogenic diabetes

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Research that mentions this SNP (2)

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents
Case reportN=82Feigerlová E. et al.(2006)· European Journal of Pediatrics

This case-control study of 82 children with asymptomatic hyperglycaemia identified genetic causes in 48% (39/82): 35 GCK mutations causing MODY2, 2 TCF1 mutations causing MODY3, 1 HNF4A mutation causing MODY1, and 1 KCNJ11 mutation (R201H) causing permanent neonatal diabetes. Additionally, 11 children (13%) had presymptomatic type 1 diabetes detected early, allowing preventive insulin therapy.

Traits studied:Asymptomatic hyperglycaemiaMODY1MODY2MODY3Permanent neonatal diabetesType 1 diabetes mellitus
Identification of 21 novel glucokinase (GCK) mutations in UK and European Caucasians with maturity-onset diabetes of the young (MODY)
AssociationN=212Thomson KL et al.(2003)· Human Mutation

Identification of 21 novel glucokinase (GCK) mutations in 212 UK and European Caucasian patients with maturity-onset diabetes of the young (MODY). Mutations were found in 29% of the cohort (61/212 patients), including 22 previously reported and 21 novel mutations (14 missense, 2 nonsense, 5 frameshift). Patients with GCK mutations presented with mild, stable hyperglycemia (5.5-8 mmol/l fasting glucose) and low oral glucose tolerance test increments, consistent with the benign GCK MODY phenotype.

Traits studied:Gestational diabetes mellitusMaturity-onset diabetes of the young (MODY)

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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