HK3 Gene - Hexokinase 3
Key enzyme in glucose metabolism with roles in glycolysis and cellular energy homeostasis
Gene Information Card
| Symbol | HK3 |
|---|---|
| Full Name | Hexokinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q35.2 |
| NCBI Gene ID | 3101 ncbi.nlm.nih.gov/gene/3101 |
| Ensembl ID | ENSG00000160883 |
| UniProt ID | P52790 |
| OMIM ID | 142570 |
| HGNC ID | 4925 |
| Aliases | HKIII, HXK3, hexokinase type III |
Description
HK3 encodes hexokinase 3, one of four hexokinase isozymes that catalyze the first step of glycolysis: phosphorylation of glucose to glucose-6-phosphate. Hexokinase 3 is predominantly expressed in tissues with high metabolic demand and is regulated by glucose-6-phosphate inhibition. It plays a critical role in glucose sensing and energy metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hexokinase deficiency (hemolytic anemia) | Loss-of-function mutations in HK3 impair erythrocyte glycolysis, leading to reduced ATP production and shortened red cell lifespan | ClinVar, OMIM |
| Type 2 diabetes | Altered HK3 expression in insulin-sensitive tissues may contribute to glucose dysregulation | NCBI Gene, literature |
| Cancer (various) | Overexpression of HK3 in certain tumors supports aerobic glycolysis (Warburg effect) | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Skeletal muscle | 8.3 | Low |
| Heart | 6.7 | Low |
| Kidney | 10.1 | Medium |
| Brain | 4.2 | Low |
| Pancreas | 9.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| K562 | 7.1 | Chronic myelogenous leukemia cell line |
| A549 | 5.6 | Lung carcinoma cell line |
| MCF7 | 3.2 | Breast adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1439G>A (p.Arg480His) | Missense | Rare | Reduced enzyme activity; associated with hemolytic anemia |
| c.1006C>T (p.Arg336Trp) | Missense | Rare | Impaired glucose binding; loss of function |
| c.1661A>G (p.Asn554Ser) | Missense | Unknown | Potential gain of function; observed in cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg480His and p.Arg336Trp reduce catalytic activity, leading to metabolic deficiencies and hemolytic anemia.
Gain of Function (GOF)
p.Asn554Ser may increase enzyme activity, supporting enhanced glycolysis in cancer cells.
Dominant Negative (DN)
No dominant-negative mutations reported for HK3.
View complete mutation data：
Gene Ontology (GO)
| • hexokinase activity (GO:0004396) | • ATP binding (GO:0005524) |
| • carbohydrate metabolic process (GO:0005975) | • glycolytic process (GO:0006096) |
| • phosphotransferase activity (GO:0016773) | • cytoplasm (GO:0005737) |
Pathways
• Glycolysis (Reactome: R-HSA-70171)
• Glucose metabolism (KEGG: hsa00010)
• Hexose phosphorylation (Reactome: R-HSA-70326)
Protein Summary
Hexokinase 3 is a 923-amino acid protein (molecular weight ~102 kDa) that phosphorylates glucose to glucose-6-phosphate, the first committed step of glycolysis. It is allosterically inhibited by its product, glucose-6-phosphate. Unlike hexokinase 1 and 2, HK3 lacks a mitochondrial binding domain and is primarily cytosolic. Its expression is highest in liver, kidney, and pancreas, and it is implicated in metabolic disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HK3 Knockout HEK293 Cell Line | EDJ-KQ916 | Human | 3101 | Details Get a Quote |
| HK3 Knockout HeLa Cell Line | EDJ-KQ53517 | Human | 3101 | Details Get a Quote |
| HK3 Knockout A-549 Cell Line | EDJ-KQ61986 | Human | 3101 | Details Get a Quote |
| HK3 Knockout HCT 116 Cell Line | EDJ-KQ70468 | Human | 3101 | Details Get a Quote |
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