HK1

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific.

hexokinase 1

Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively) (PubMed:1637300, PubMed:25316723, PubMed:27374331).

Does not phosphorylate N-acetyl-D-glucosamine (PubMed:27374331).

Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity).

Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan (PubMed:27374331).

When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331).

Canonical glycolysis Source: Reactome
Carbohydrate phosphorylation Source: CAFA
Cellular glucose homeostasis Source: GO_Central
Establishment of protein localization to mitochondrion Source: ParkinsonsUK-UCL
Fructose 6-phosphate metabolic process Source: UniProtKB
Glucose 6-phosphate metabolic process Source: UniProtKB
Glycolytic process Source: GO_Central
Inflammatory response Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Maintenance of protein location in mitochondrion Source: ParkinsonsUK-UCL
Mannose metabolic process Source: UniProtKB
Positive regulation of cytokine production involved in immune response Source: Ensembl
Positive regulation of interleukin-1 beta production Source: Ensembl

Mitochondrion outer membrane; Cytosol. The mitochondrial-binding peptide (MBP) region promotes association with the mitochondrial outer membrane (Probable). Dissociates from the mitochondrial outer membrane following inhibition by N-acetyl-D-glucosamine, leading to relocation to the cytosol (PubMed:27374331).

Hexokinase deficiency (HK deficiency):
Rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature.
Neuropathy, hereditary motor and sensory, Russe type (HMSNR):
An autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.
Retinitis pigmentosa 79 (RP79):
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP79 inheritance is autosomal dominant.
Neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA):
A disorder characterized by global developmental delay, speech delay, intellectual disability, structural brain abnormalities, and visual impairments including retinitis pigmentosa and optic atrophy.