AlphaFold predicted structure
GCK · P35557
Mean pLDDT
93.7/ 100
Very high
465 residues
Confidence breakdown
- Very high(≥ 90)85%
- Confident(70–90)13%
- Low(50–70)2%
- Very low(< 50)0%
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AlphaFold (Jumper et al., 2021) · CC BY 4.0
GCK
Chr 7p13glucokinase
- Aliases:
- HK4, HKIV
- MANE:
- ENST00000403799.8
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Congenital hyperinsulinism
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedDiabetes with additional phenotypes suggestive of a monogenic aetiology
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalFamilial diabetes
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalGlucokinase-related fasting hyperglycaemia
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownMonogenic diabetes
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalNeonatal diabetes
BOTH monoallelic and biallelic, autosomal or pseudoautosomalIntellectual disability
Multi-organ autoimmune diabetes
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Disease associations (Open Targets)
MODY
0.86type 2 diabetes mellitus
0.86permanent neonatal diabetes mellitus 1
0.81hyperinsulinism due to glucokinase deficiency
0.80diabetes mellitus
0.78maturity-onset diabetes of the young type 2
0.74maturity-onset diabetes of the young
0.70monogenic diabetes
0.69permanent neonatal diabetes mellitus
0.68transient neonatal diabetes, dominant/recessive
0.51
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Mitogen-activated protein kinase kinase kinase kinase 2
Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443)
Diseases associated with GCK
Curated MONDO disease pages that list GCK among their top associated genes.