KHK (Ketohexokinase) Gene
Key enzyme in fructose metabolism and its role in metabolic disorders
Gene Information Card
| Symbol | KHK |
|---|---|
| Full Name | Ketohexokinase |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 3795 ncbi.nlm.nih.gov/gene/3795 |
| Ensembl ID | ENSG00000138031 |
| UniProt ID | P50053 |
| OMIM ID | 229800 |
| HGNC ID | 6315 |
| Aliases | Fructokinase, Ketohexokinase |
Description
The KHK gene encodes ketohexokinase, an enzyme that catalyzes the phosphorylation of fructose to fructose-1-phosphate, the first step in fructose metabolism. This enzyme is primarily expressed in the liver, kidney, and small intestine. Mutations in KHK cause essential fructosuria, a benign autosomal recessive disorder characterized by fructose excretion in urine. KHK exists as two isoforms (KHK-A and KHK-C) with different kinetic properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Essential fructosuria | Loss-of-function mutations in KHK impair fructose phosphorylation, leading to fructose accumulation and urinary excretion | OMIM #229800 |
| Metabolic syndrome (associated) | Altered KHK activity may contribute to fructose-induced lipogenesis and insulin resistance | NCBI Gene review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 24.5 | High |
| Kidney | 18.2 | High |
| Small intestine | 15.8 | High |
| Pancreas | 3.1 | Low |
| Adipose tissue | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 22.1 | Liver cancer cell line |
| HEK293 | 8.4 | Embryonic kidney cells |
| Caco-2 | 12.3 | Colorectal adenocarcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.663C>A (p.Asn221Lys) | Missense | Rare | Loss of enzyme activity |
| c.940G>A (p.Gly314Arg) | Missense | Rare | Loss of enzyme activity |
| c.1159C>T (p.Arg387*) | Nonsense | Rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most KHK mutations cause loss of enzymatic activity, leading to essential fructosuria.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • fructokinase activity |
| • ketohexokinase activity | • fructose metabolic process |
| • carbohydrate phosphorylation |
Pathways
• Fructose and mannose metabolism (KEGG: hsa00051)
• Fructose metabolism (Reactome: R-HSA-5657560)
Protein Summary
Ketohexokinase (KHK) is a 298-amino acid enzyme that phosphorylates fructose using ATP. It exists as two splice variants: KHK-A (low affinity) and KHK-C (high affinity). The enzyme is critical for hepatic fructose metabolism and is implicated in metabolic diseases when dysregulated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KHK Knockout HEK293 Cell Line | EDJ-KQ4274 | Human | 3795 | Details Get a Quote |
| KHK Knockout A-549 Cell Line | EDJ-KQ27976 | Human | 3795 | Details Get a Quote |
| KHK Knockout HCT 116 Cell Line | EDJ-KQ27978 | Human | 3795 | Details Get a Quote |
| KHK Knockout HeLa Cell Line | EDJ-KQ27979 | Human | 3795 | Details Get a Quote |
