ArticleDiabetes care2012
Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.
Article in Diabetes care, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- Functional Characterization of Glucokinase Variants to Aid Clinical Interpretation of Monogenic Diabetes.International journal of molecular sciences · 2025Article
- A comprehensive map of human glucokinase variant activity.Genome biology · 2023Article
- A Comprehensive Analysis of Hungarian MODY Patients-Part II: Glucokinase MODY Is the Most Prevalent Subtype Responsible for about 70% of Confirmed Cases.Life (Basel, Switzerland) · 2021Article
- Large-scale in-silico statistical mutagenesis analysis sheds light on the deleteriousness landscape of the human proteome.Scientific reports · 2018Article
- Evidence-based tailoring of bioinformatics approaches to optimize methods that predict the effects of nonsynonymous amino acid substitutions in glucokinase.Scientific reports · 2017Article
- Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry.Diabetologia · 2017Article
- GCK-MODY in the US National Monogenic Diabetes Registry: frequently misdiagnosed and unnecessarily treated.Acta diabetologica · 2016Article
- Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.Human molecular genetics · 2014Article
- Reclassification of diabetes etiology in a family with multiple diabetes phenotypes.The Journal of clinical endocrinology and metabolism · 2014Article
- Insights into the genetic susceptibility to type 2 diabetes from genome-wide association studies of glycaemic traits.Current diabetes reports · 2014Review
- When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes.The review of diabetic studies : RDSReview
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveTo demonstrate the importance of using a combined genetic and functional approach to correctly interpret a genetic test for monogenic diabetes. RESEARCH DESIGN AND
methodsWe identified three probands with a phenotype consistent with maturity-onset diabetes of the young (MODY) subtype GCK-MODY, in whom two potential pathogenic mutations were identified: [R43H/G68D], [E248 K/I225M], or [G261R/D217N]. Allele-specific PCR and cosegregation were used to determine phase. Single and double mutations were kinetically characterized.
resultsThe mutations occurred in cis (double mutants) in two probands and in trans in one proband. Functional studies of all double mutants revealed inactivating kinetics. The previously reported GCK-MODY mutations R43H and G68D were inherited from an affected father and unaffected mother, respectively. Both our functional and genetic studies support R43H as the cause of GCK-MODY and G68D as a neutral rare variant.
conclusionsThese data highlight the need for family/functional studies, even for previously reported pathogenic mutations.
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