HK1 Gene - Hexokinase 1
Key regulator of glucose metabolism and erythroid development
Gene Information Card
| Symbol | HK1 |
|---|---|
| Full Name | Hexokinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 3098 ncbi.nlm.nih.gov/gene/3098 |
| Ensembl ID | ENSG00000156515 |
| UniProt ID | P19367 |
| OMIM ID | 142600 |
| HGNC ID | 4922 |
| Aliases | HK1-ta, HK1-tb, HK1-tc, HKD, HXK1, hexokinase type I |
Description
HK1 encodes hexokinase 1, the first enzyme in glycolysis that phosphorylates glucose to glucose-6-phosphate. It is ubiquitously expressed, with highest levels in brain, erythrocytes, and kidney. The enzyme is allosterically inhibited by glucose-6-phosphate and plays a critical role in cellular energy homeostasis. Mutations in HK1 are associated with hemolytic anemia due to hexokinase deficiency and Charcot-Marie-Tooth disease type 4G (CMT4G).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hemolytic anemia due to hexokinase deficiency | Loss-of-function mutations reduce enzyme activity, impairing erythrocyte glycolysis and ATP production, leading to premature red cell destruction | OMIM #235700; ClinVar |
| Charcot-Marie-Tooth disease type 4G (CMT4G) | Missense mutations cause dominant-negative or gain-of-function effects, disrupting peripheral nerve myelination and axonal function | OMIM #605285; ClinVar |
| Retinitis pigmentosa (rare association) | Altered glucose metabolism in retinal cells due to HK1 deficiency | OMIM #268000; NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Erythrocytes | 22.1 | High |
| Kidney | 18.3 | Medium |
| Liver | 12.7 | Medium |
| Skeletal muscle | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (erythroleukemia) | 35.2 | High expression |
| HEK293 (embryonic kidney) | 20.1 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 25.6 | High expression |
| HepG2 (hepatocellular carcinoma) | 15.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1439G>A (p.Arg480His) | Missense | <0.01% | Reduced enzyme activity; associated with hemolytic anemia |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of function; severe hemolytic anemia |
| c.242C>T (p.Thr81Met) | Missense | <0.01% | Dominant-negative; associated with CMT4G |
| c.1034T>C (p.Leu345Pro) | Missense | <0.01% | Gain-of-function; linked to neuropathy |
Mutation functional classification
Loss of Function (LOF)
Most common; missense or nonsense mutations reduce or abolish hexokinase activity, leading to hemolytic anemia.
Gain of Function (GOF)
Rare; specific missense mutations (e.g., p.Leu345Pro) increase enzyme activity, associated with Charcot-Marie-Tooth disease.
Dominant Negative (DN)
Mutations such as p.Thr81Met interfere with wild-type enzyme function, causing neuropathy.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • hexokinase activity (GO:0004396) |
| • carbohydrate metabolic process (GO:0005975) | • glycolytic process (GO:0006096) |
| • cytosol (GO:0005829) | • mitochondrion (GO:0005739) |
Pathways
• Glycolysis / Gluconeogenesis (KEGG: hsa00010)
• Pentose phosphate pathway (KEGG: hsa00030)
• Insulin signaling pathway (KEGG: hsa04910)
Protein Summary
Hexokinase 1 is a 100 kDa enzyme that catalyzes the first committed step of glycolysis. It exists in multiple isoforms generated by alternative splicing. The protein has two homologous domains, with the catalytic site in the C-terminal domain. It binds to the outer mitochondrial membrane via a porin-binding domain, coupling glycolysis to oxidative phosphorylation. HK1 is essential for erythrocyte survival and neuronal energy metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPHK1 Knockout HEK293 Cell Line | EDJ-KQ1066 | Human | 8877 | Details Get a Quote |
| HK1 Knockout HEK293 Cell Line | EDJ-KQ1506 | Human | 3098 | Details Get a Quote |
| SPHK1 Knockout A-549 Cell Line | EDJ-KQ20196 | Human | 8877 | Details Get a Quote |
| SPHK1 Knockout HCT 116 Cell Line | EDJ-KQ20197 | Human | 8877 | Details Get a Quote |
| HK1 Knockout A-549 Cell Line | EDJ-KQ21124 | Human | 3098 | Details Get a Quote |
| HK1 Knockout HCT 116 Cell Line | EDJ-KQ21125 | Human | 3098 | Details Get a Quote |
| HK1 Knockout HeLa Cell Line | EDJ-KQ21126 | Human | 3098 | Details Get a Quote |
| SPHK1 Knockout HeLa Cell Line | EDJ-KQ18852 | Human | 8877 | Details Get a Quote |
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