KHK ketohexokinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: KHKprovided by HGNC
Official Full Name: ketohexokinaseprovided by HGNC
Primary source: HGNC:HGNC:6315
See related: Ensembl:ENSG00000138030 MIM:614058; AllianceGenome:HGNC:6315
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FRUCTU
Summary: This gene encodes ketohexokinase that catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Expression: Biased expression in kidney (RPKM 77.2), liver (RPKM 59.5) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p23.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (27086772..27100762)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (27128445..27142438)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (27309640..27323630)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.
Title: Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.
GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer.
Title: GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer.
USP36 promotes tumor growth of non-small cell lung cancer via increasing KHK-A expression by regulating c-MYC-hnRNPH1/H2 axis.
Title: USP36 promotes tumor growth of non-small cell lung cancer via increasing KHK-A expression by regulating c-MYC-hnRNPH1/H2 axis.
KHK-A promotes the proliferation of oesophageal squamous cell carcinoma through the up-regulation of PRPS1.
Title: KHK-A promotes the proliferation of oesophageal squamous cell carcinoma through the up-regulation of PRPS1.
Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants.
Title: Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants.
Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer.
Title: Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer.
KHK-A has a role in antioxidative stress and hepatocellular carcinoma development that involves phosphorylating p62
Title: The protein kinase activity of fructokinase A specifies the antioxidant responses of tumor cells by phosphorylating p62.
Data indicate metabolic enzymes NAD kinase and ketohexokinase as candidate metabolic gene targets, and the chromatin remodeling protein INO80C as a tumor suppressor in KRAS(MUT) colorectal tumor xenograft.
Title: Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers.
Angelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis were the top four botanical candidiates identified with inhibitory activity against ketohexokinase-C.
Title: Bioactivity-Guided Identification of Botanical Inhibitors of Ketohexokinase.
compared with normal hepatocytes, hepatocellular carcinoma (HCC) cells markedly reduce the rate of fructose metabolism and the level of reactive oxygen species, as a result of a c-Myc-dependent and heterogeneous nuclear ribonucleoprotein (hnRNP) H1- and H2-mediated switch from expression of the high-activity fructokinase (KHK)-C to the low-activity KHK-A isoform.
Title: A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Essential fructosuria MedGen: C0268160 OMIM: 229800 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D2S2614 (e-PCR)
- UniSTS:41755

SHGC-12022 (e-PCR)
- UniSTS:48449

G19822 (e-PCR)
- UniSTS:35670

A001Z30 (e-PCR)
- UniSTS:35671

WI-15611 (e-PCR)
- UniSTS:21363

STS-Z41432 (e-PCR)
- UniSTS:71605

GDB:335751 (e-PCR)
- UniSTS:156601

RH70916 (e-PCR)
- UniSTS:5050

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables fructose binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables ketohexokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ketohexokinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in carbohydrate phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in fructose metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in fructose metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in fructose metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of glycogen metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to fructose	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to glucose	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to insulin	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to sucrose	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to zinc ion	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed

General protein information

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Preferred Names: ketohexokinase

Names: fructokinase; hepatic fructokinase; testicular tissue protein Li 102

NP_000212.1

EC 2.7.1.3

NP_006479.1

EC 2.7.1.3

XP_005264351.1

EC 2.7.1.3

XP_005264353.1

EC 2.7.1.3

XP_005264355.1

EC 2.7.1.3

XP_006712071.1

EC 2.7.1.3

XP_006712072.1

EC 2.7.1.3

XP_006712073.1

EC 2.7.1.3

XP_006712074.1

EC 2.7.1.3

XP_006712075.1

EC 2.7.1.3

XP_006712076.1

EC 2.7.1.3

XP_006712077.1

EC 2.7.1.3

XP_016859549.1

EC 2.7.1.3

XP_016859550.1

EC 2.7.1.3

XP_054197919.1

EC 2.7.1.3

XP_054197920.1

EC 2.7.1.3

XP_054197921.1

EC 2.7.1.3

XP_054197922.1

EC 2.7.1.3

XP_054197923.1

EC 2.7.1.3

XP_054197924.1

EC 2.7.1.3

XP_054197925.1

EC 2.7.1.3

XP_054197926.1

EC 2.7.1.3

XP_054197927.1

EC 2.7.1.3

XP_054197928.1

EC 2.7.1.3

XP_054197929.1

EC 2.7.1.3

XP_054197930.1

EC 2.7.1.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012199.2 RefSeqGene

Range

5030..19020

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000221.3 → NP_000212.1 ketohexokinase isoform a

See identical proteins and their annotated locations for NP_000212.1

Status: REVIEWED

Description

Transcript Variant: This variant utilizes the alternate exon 3a and encodes isoform a, which exhibits lower enzymatic activity than isoform b.

Source sequence(s)

AC013403

Consensus CDS

CCDS1734.1

UniProtKB/TrEMBL

A0A140VJM6, Q53G56

Related

ENSP00000260599.6, ENST00000260599.11

Conserved Domains (1) summary

cd01939
Location:5 → 295

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
NM_006488.3 → NP_006479.1 ketohexokinase isoform b

See identical proteins and their annotated locations for NP_006479.1

Status: REVIEWED

Description

Transcript Variant: This variant utilizes the alternate exon 3c and encodes isoform b, which exhibits higher enzymatic activity than isoform a.

Source sequence(s)

AC013403

Consensus CDS

CCDS1735.1

UniProtKB/Swiss-Prot

P50053, Q6IBK2, Q99532, Q9BRJ3, Q9UMN1

Related

ENSP00000260598.5, ENST00000260598.10

Conserved Domains (1) summary

cd01939
Location:5 → 295

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

27086772..27100762

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005264294.5 → XP_005264351.1 ketohexokinase isoform X3

UniProtKB/TrEMBL

Q53G56

Conserved Domains (1) summary

cd01939
Location:5 → 341

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
XM_005264296.5 → XP_005264353.1 ketohexokinase isoform X8

UniProtKB/TrEMBL

Q53G56

Conserved Domains (1) summary

cd01939
Location:5 → 296

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
XM_017004060.3 → XP_016859549.1 ketohexokinase isoform X4

UniProtKB/TrEMBL

C9JDL1, Q53G56

Related

ENSP00000404741.2, ENST00000429697.2
XM_017004061.3 → XP_016859550.1 ketohexokinase isoform X10

UniProtKB/TrEMBL

Q53G56
XM_005264298.5 → XP_005264355.1 ketohexokinase isoform X12

See identical proteins and their annotated locations for XP_005264355.1

Conserved Domains (1) summary

cd01939
Location:5 → 211

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
XM_006712008.5 → XP_006712071.1 ketohexokinase isoform X1

Conserved Domains (1) summary

cl00192
Location:5 → 235

ribokinase_pfkB_like; ribokinase/pfkB superfamily: Kinases that accept a wide variety of substrates, including carbohydrates and aromatic small molecules, all are phosphorylated at a hydroxyl group. The superfamily includes ribokinase, fructokinase, ketohexokinase, ...
XM_006712010.5 → XP_006712073.1 ketohexokinase isoform X5

Conserved Domains (1) summary

cd01939
Location:5 → 190

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
XM_006712009.5 → XP_006712072.1 ketohexokinase isoform X2

Conserved Domains (1) summary

cl00192
Location:5 → 234

ribokinase_pfkB_like; ribokinase/pfkB superfamily: Kinases that accept a wide variety of substrates, including carbohydrates and aromatic small molecules, all are phosphorylated at a hydroxyl group. The superfamily includes ribokinase, fructokinase, ketohexokinase, ...
XM_006712012.5 → XP_006712075.1 ketohexokinase isoform X7

Conserved Domains (1) summary

cd01939
Location:5 → 189

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
XM_006712011.5 → XP_006712074.1 ketohexokinase isoform X6

Conserved Domains (1) summary

cd01939
Location:5 → 189

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
XM_006712013.5 → XP_006712076.1 ketohexokinase isoform X9

Conserved Domains (1) summary

cl00192
Location:5 → 144

ribokinase_pfkB_like; ribokinase/pfkB superfamily: Kinases that accept a wide variety of substrates, including carbohydrates and aromatic small molecules, all are phosphorylated at a hydroxyl group. The superfamily includes ribokinase, fructokinase, ketohexokinase, ...
XM_006712014.5 → XP_006712077.1 ketohexokinase isoform X11

Conserved Domains (1) summary

cl00192
Location:5 → 105

ribokinase_pfkB_like; ribokinase/pfkB superfamily: Kinases that accept a wide variety of substrates, including carbohydrates and aromatic small molecules, all are phosphorylated at a hydroxyl group. The superfamily includes ribokinase, fructokinase, ketohexokinase, ...