HK2 (Hexokinase 2)
A key glycolytic enzyme implicated in cancer metabolism and insulin resistance
Gene Information Card
| Symbol | HK2 |
|---|---|
| Full Name | Hexokinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p12 |
| NCBI Gene ID | 3099 ncbi.nlm.nih.gov/gene/3099 |
| Ensembl ID | ENSG00000159399 |
| UniProt ID | P52789 |
| OMIM ID | 601125 |
| HGNC ID | 4923 |
| Aliases | HKII, HXK2, hexokinase type II |
Description
HK2 encodes hexokinase 2, the first rate-limiting enzyme of glycolysis that phosphorylates glucose to glucose-6-phosphate. It is highly expressed in insulin-sensitive tissues (skeletal muscle, heart, adipose) and is frequently overexpressed in cancers, contributing to the Warburg effect. HK2 binds to the mitochondrial outer membrane via VDAC, coupling glycolysis to oxidative phosphorylation and inhibiting apoptosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of HK2 promotes aerobic glycolysis (Warburg effect), providing metabolic advantage and resistance to apoptosis. | COSMIC; PMID: 22955980 |
| Type 2 diabetes | Reduced HK2 expression in skeletal muscle impairs glucose disposal and contributes to insulin resistance. | OMIM 601125; PMID: 10648001 |
| HK2 deficiency (hemolytic anemia) | Biallelic loss-of-function mutations in HK2 cause nonspherocytic hemolytic anemia due to impaired erythrocyte glycolysis. | ClinVar; PMID: 28498831 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 28.5 | High |
| Heart | 22.1 | High |
| Adipose tissue | 15.3 | Medium |
| Liver | 2.4 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.7 | Cervical cancer cell line |
| MCF7 | 18.3 | Breast cancer cell line |
| A549 | 21.0 | Lung cancer cell line |
| HepG2 | 6.5 | Hepatocellular carcinoma cell line |
| K562 | 3.2 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1493G>A (p.Arg498His) | Missense | Rare | Impaired catalytic activity; associated with hemolytic anemia (ClinVar) |
| c.1186C>T (p.Arg396Trp) | Missense | Rare | Reduced enzyme stability; reported in HK2 deficiency |
| Amplification | Copy number gain | Frequent in cancers | Overexpression in glioblastoma, breast, and lung cancers (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg498His, p.Arg396Trp) reduce or abolish hexokinase activity, leading to hemolytic anemia.
Gain of Function (GOF)
Gene amplification and transcriptional upregulation increase HK2 protein levels, enhancing glycolysis in cancer cells.
Dominant Negative (DN)
Not reported for HK2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004396 - hexokinase activity | • GO:0005524 - ATP binding |
| • GO:0005975 - carbohydrate metabolic process | • GO:0006096 - glycolytic process |
| • GO:0005739 - mitochondrion | • GO:0005829 - cytosol |
Pathways
• Glycolysis / Gluconeogenesis (KEGG: hsa00010)
• HIF-1 signaling pathway (KEGG: hsa04066)
• Central carbon metabolism in cancer (KEGG: hsa05230)
• Insulin signaling pathway (KEGG: hsa04910)
Protein Summary
Hexokinase 2 (HK2) is a 917-amino acid protein (102 kDa) that catalyzes the ATP-dependent phosphorylation of glucose. It contains an N-terminal mitochondrial-binding domain that anchors it to the outer mitochondrial membrane via VDAC, allowing direct access to ATP and coupling glycolysis to mitochondrial function. HK2 is a key mediator of the Warburg effect in cancer and is a target for therapeutic inhibition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPHK2 Knockout HEK293 Cell Line | EDJ-KQ1413 | Human | 56848 | Details Get a Quote |
| HK2 Knockout HEK293 Cell Line | EDJ-KQ1507 | Human | 3099 | Details Get a Quote |
| SPHK2 Knockout A-549 Cell Line | EDJ-KQ20951 | Human | 56848 | Details Get a Quote |
| SPHK2 Knockout HCT 116 Cell Line | EDJ-KQ20952 | Human | 56848 | Details Get a Quote |
| SPHK2 Knockout HeLa Cell Line | EDJ-KQ20953 | Human | 56848 | Details Get a Quote |
| HK2 Knockout HCT 116 Cell Line | EDJ-KQ21127 | Human | 3099 | Details Get a Quote |
| HK2 Knockout HeLa Cell Line | EDJ-KQ21128 | Human | 3099 | Details Get a Quote |
| HK2 Knockout A-549 Cell Line | EDJ-KQ61985 | Human | 3099 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
