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Photo: KG Pressfoto

Marju Orho-Melander


Photo: KG Pressfoto

GCKR : How genetic variation across the allelic spectrum influences protein function and metabolic traits in humans


  • Marju Orho-Melander
  • Anna L. Gloyn

Summary, in English

Genome-wide association studies (GWAS) have generated considerable interest in glucokinase regulatory protein (GKRP; gene name GCKR) which is an inhibitor of hepatic glucokinase (GCK), an enzyme that plays a critical role in glucose update and disposal in liver. From the initial discovery of GCKR variants associated with triglyceride and glucose levels through the identification of pleiotropic associations with a wide variety of metabolic phenotypes, we have learned a great deal about the importance of GKRP as a critical node in hepatic metabolism. GKRP remains one of the few well-studied GWAS loci where attempts have been made to understand the functional as well as the phenotypic impact of genetic variants across the allelic spectrum. Given the interest in developing liver-specific glucokinase activators and small molecules which disrupt the GKRP:GCK interaction for the treatment of type 2 diabetes, these genetic insights provide a wealth of information regarding efficacy and potential adverse on-target effects in humans.


  • Diabetes - Cardiovascular Disease
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation

Document type

Book chapter


Springer International Publishing


  • Medical Genetics



Research group

  • Diabetes - Cardiovascular Disease


  • ISBN: 9783319015743
  • ISBN: 9783319015736