Diabetes - neonatal onset

Gene: GCK

Green List (high evidence)

GCK (glucokinase)
EnsemblGeneIds (GRCh38): ENSG00000106633
EnsemblGeneIds (GRCh37): ENSG00000106633
OMIM: 138079, Gene2Phenotype
GCK is in 8 panels

4 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: Previous phenotype:
MODY, type II, 125851;Diabetes mellitus, noninsulin-dependent, late onset, 125853;Diabetes mellitus, gestational, 125851;Hyperinsulinemic hypoglycemia, familial, 3, 602485;Diabetes mellitus, permanent neonatal, 606176;Permanent Neonatal Diabetes Mellitus;Transient Neonatal Diabetes, Recessive;Permanent neonatal diabetes;Fasting hyperglycaemia, permanent neonatal diabetes
Created: 3 Mar 2021, 1:21 p.m. | Last Modified: 3 Mar 2021, 1:21 p.m.
Panel Version: 2.11
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: GCK; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Fasting hyperglycaemia, permanent neonatal diabetes.
Created: 11 Jan 2019, 4:27 p.m.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

Elisa De Franco (University of Exeter Medical School)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as Ready: 25th May 2017.
Created: 25 May 2017, 10:17 a.m.
Comment on list classification: Kept rating as Green: 2 cases (Norweigan and Italian) of permanent neonatal diabetes (MIM:606176) plus multiple cases of neonatal hypoglycemia. Rated green by expert reviewer, and part of Exeter neonatal diabetes screen.
Created: 25 May 2017, 10:17 a.m.
Comment on mode of inheritance: Heterozygous GCK mutations cause MODY, and homozygous mutations cause neonatal diabetes. Based on advice from Elisa De-Franco (University of Exeter Medical School), I have changed the mode-of-inheritance from biallelic to both biallelic and monoallelic: in patients with heterozygous GCK mutations the fasting hyperglycemia is present from birth. So it is possible that (rarely) a patient is incidentally found to have high blood sugars in the neonatal period and thought to have neonatal diabetes, but they actually have GCK MODY.
Created: 25 May 2017, 10:15 a.m.
Comment on mode of inheritance: Heterozygous GCK mutations cause MODY, and homozygous mutations cause neonatal diabetes. Based on advice from Elisa De-Franco (University of Exeter Medical School), I have changed the mode-of-inheritance from biallelic to both biallelic and monoallelic: in patients with heterozygous GCK mutations the fasting hyperglycemia is present from birth. So it is possible that (rarely) a patient is incidentally found to have high blood sugars in the neonatal period and thought to have neonatal diabetes, but they actually have GCK MODY.
Created: 25 May 2017, 10:15 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • MODY, type II, OMIM:125851
  • Diabetes mellitus, noninsulin-dependent, late onset, OMIM:125853
  • Hyperinsulinemic hypoglycemia, familial, 3, OMIM:602485
  • Diabetes mellitus, permanent neonatal 1, OMIM:606176
  • Transient Neonatal Diabetes Mellitus (disease), MONDO:0020525 (recessive)
OMIM
138079
Clinvar variants
Variants in GCK
Penetrance
Complete
Panels with this gene

History Filter Activity

3 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: GCK were changed from MODY, type II, 125851; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Diabetes mellitus, gestational, 125851; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Recessive; Permanent neonatal diabetes; Fasting hyperglycaemia, permanent neonatal diabetes to MODY, type II, OMIM:125851; Diabetes mellitus, noninsulin-dependent, late onset, OMIM:125853; Hyperinsulinemic hypoglycemia, familial, 3, OMIM:602485; Diabetes mellitus, permanent neonatal 1, OMIM:606176; Transient Neonatal Diabetes Mellitus (disease), MONDO:0020525 (recessive)

15 Jul 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: GCK were changed from MODY, type II, 125851; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Diabetes mellitus, gestational, 125851; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Recessive; Permanent neonatal diabetes to MODY, type II, 125851; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Diabetes mellitus, gestational, 125851; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Recessive; Permanent neonatal diabetes; Fasting hyperglycaemia, permanent neonatal diabetes

11 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to GCK. Rating Changed from Green List (high evidence) to Green List (high evidence)

31 May 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

Promoted panel to Version 1: 31st May 2017. This panel is largely aligned with the Exeter Molecular Genetics Laboratory neonatal diabetes screen. Note that 8 genes feature on the Exeter 8-gene panel for patients with 'neonatal diabetes and autoimmune disease' (FOXP3, IL2RA, ITCH, LRBA, SIRT1, STAT1, STAT3 and STAT5). ITCH, SIRT1, STAT1 and STAT5A/B do not feature on this panel following correspondance with Elisa De-Franco (University of Exeter Medical School) that, at the time of curation, none of the patients with mutations in ITCH, SIRT1, STAT1 and STAT5b had diabetes diagnosed in the neonatal period, and therefore there is currently insufficient evidence to include these genes in this neonatal diabetes panel.

25 May 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

25 May 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

25 May 2017, Gel status: 3

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GCK was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

25 May 2017, Gel status: 3

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GCK was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

17 Aug 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

GCK was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing

17 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Aug 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

GCK was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN

17 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene GCK was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

GCK was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Illumina TruGenome Clinical Sequencing Services

17 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

GCK was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Radboud University Medical Center, Nijmegen