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HK2 hexokinase 2 [ Homo sapiens (human) ]

Gene ID: 3099, updated on 5-Jul-2025
Official Symbol
HK2provided by HGNC
Official Full Name
hexokinase 2provided by HGNC
Primary source
HGNC:HGNC:4923
See related
Ensembl:ENSG00000159399 MIM:601125; AllianceGenome:HGNC:4923
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
HKII; HXK2
Summary
Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 2, the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells. [provided by RefSeq, Apr 2009]
Expression
Broad expression in fat (RPKM 34.4), colon (RPKM 24.2) and 19 other tissues See more
Orthologs
mouse all
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See HK2 in Genome Data Viewer
Location:
2p12
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (74834127..74893359)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (74842983..74902233)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (75061254..75120486)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102724497 Neighboring gene uncharacterized LOC102724482 Neighboring gene ribosomal protein S28 pseudogene 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:75017750-75017897 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11673 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11674 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:75061972-75062848 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:75064008-75064523 Neighboring gene Sharpr-MPRA regulatory region 11570 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16083 Neighboring gene HK2 divergent transcript Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:75082772-75083312 Neighboring gene uncharacterized LOC105374809 Neighboring gene long intergenic non-protein coding RNA 1291 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:75185356-75185856 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:75185857-75186357 Neighboring gene DNA polymerase epsilon 4, accessory subunit

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL. Bhalla K, et al. Sci Rep, 2018 Jan 15. PMID 29335581, Free PMC Article
  2. Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death. Xia HG, et al. J Cell Biol, 2015 Aug 31. PMID 26323688, Free PMC Article
  3. Human coronary thrombus formation is associated with degree of plaque disruption and expression of tissue factor and hexokinase II. Okuyama N, et al. Circ J, 2015. PMID 26346032
  4. The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression. Ho N, et al. Biosci Rep, 2016 Jan 6. PMID 26740252, Free PMC Article
  5. Inhibition of Lung Carcinoma A549 Cell Growth by Knockdown of Hexokinase 2 In Situ and In Vivo. Xi F, et al. Oncol Res, 2016 Jan 21. PMID 26802651, Free PMC Article

See all (318) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Hexokinase 2 nonmetabolic function-mediated phosphorylation of IkappaBalpha enhances pancreatic ductal adenocarcinoma progression.
    Title: Hexokinase 2 nonmetabolic function-mediated phosphorylation of IκBα enhances pancreatic ductal adenocarcinoma progression.
  2. RNA-binding protein SORBS2 increases human trophoblast cell migration via stabilizing HK2 mRNA in preeclampsia.
    Title: RNA-binding protein SORBS2 increases human trophoblast cell migration via stabilizing HK2 mRNA in preeclampsia.
  3. CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.
    Title: CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.
  4. HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.
    Title: HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.
  5. Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.
    Title: Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.
  6. The effect and mechanism of hexokinase-2 on cisplatin resistance in lung cancer cells A549.
    Title: The effect and mechanism of hexokinase-2 on cisplatin resistance in lung cancer cells A549.
  7. A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma.
    Title: A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma.
  8. The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.
    Title: The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.
  9. PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/beta-catenin signaling.
    Title: PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/β-catenin signaling.
  10. [Expression and Prognostic Impact of HK2 in Bone Marrow of Patients with Newly Diagnosed Acute Myeloid Leukemia].
    Title: [Expression and Prognostic Impact of HK2 in Bone Marrow of Patients with Newly Diagnosed Acute Myeloid Leukemia].
Submit: New GeneRIF Correction See all GeneRIFs (216)

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

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein interactions

Protein Gene Interaction Pubs
Rev rev HIV-1 Rev interacting protein, hexokinase 2 (HK2), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells PubMed
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of hexokinase 2 (HK2) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed

Go to the HIV-1, Human Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • DKFZp686M1669

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables D-glucose binding IEA
Inferred from Electronic Annotation
more info
  
enables catalytic activity IEA
Inferred from Electronic Annotation
more info
  
enables fructokinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables fructokinase activity IEA
Inferred from Electronic Annotation
more info
  
enables fructokinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables glucokinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables glucokinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables glucokinase activity IEA
Inferred from Electronic Annotation
more info
  
enables glucokinase activity TAS
Traceable Author Statement
more info
  
enables hexokinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables hexokinase activity IEA
Inferred from Electronic Annotation
more info
  
enables hexokinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables phosphotransferase activity, alcohol group as acceptor IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transferase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within apoptotic mitochondrial changes IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within apoptotic mitochondrial changes IEA
Inferred from Electronic Annotation
more info
  
involved_in canonical glycolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in canonical glycolysis TAS
Traceable Author Statement
more info
  
involved_in carbohydrate derivative metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in carbohydrate metabolic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within carbohydrate phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in carbohydrate phosphorylation IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
  
involved_in establishment of protein localization to mitochondrion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in fructose 6-phosphate metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in fructose 6-phosphate metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in glucose 6-phosphate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glucose 6-phosphate metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glucose 6-phosphate metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glucose metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within glucose metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glucose metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glycolytic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glycolytic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glycolytic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in hexose metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular glucose homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular glucose homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in lactation IEA
Inferred from Electronic Annotation
more info
  
involved_in maintenance of protein location in mitochondrion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of mitochondrial membrane permeability IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of reactive oxygen species metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in organophosphate metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of angiogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of type 2 mitophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within regulation of D-glucose import IEA
Inferred from Electronic Annotation
more info
  
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in response to ischemia IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in centrosome IDA
Inferred from Direct Assay
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrial outer membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial outer membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrial outer membrane NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
  
located_in sarcoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
hexokinase-2
Names
hexokinase type II
hexokinase-2, muscle
hexokinase-B
muscle form hexokinase
NP_000180.2
NP_001358454.1
XP_005264337.1
XP_011531109.1
XP_016859434.1
XP_047300040.1
XP_047300041.1
XP_054197615.1
XP_054197616.1
XP_054197617.1
XP_054197618.1

NEW Try the new Transcript table

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.

mRNA and Protein(s)

  1. NM_000189.5 → NP_000180.2  hexokinase-2 isoform 1

    See identical proteins and their annotated locations for NP_000180.2

    Status: REVIEWED

    Source sequence(s)
    AC019069, AC104135
    Consensus CDS
    CCDS1956.1
    UniProtKB/Swiss-Prot
    D6W5J2, P52789, Q8WU87, Q9UN82
    UniProtKB/TrEMBL
    A8K2U2
    Related
    ENSP00000290573.2, ENST00000290573.7
    Conserved Domains (3) summary
    PTZ00107
    Location:12 → 460
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:471 → 667
    Hexokinase_1
    pfam03727
    Location:673 → 907
    Hexokinase_2

  2. NM_001371525.1 → NP_001358454.1  hexokinase-2 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC019069, AC104135
    Consensus CDS
    CCDS92787.1
    UniProtKB/TrEMBL
    E9PB90, Q68E10
    Related
    ENSP00000387140.1, ENST00000409174.1
    Conserved Domains (3) summary
    PTZ00107
    Location:1 → 432
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:443 → 639
    Hexokinase_1
    pfam03727
    Location:645 → 879
    Hexokinase_2

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

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    74834127..74893359
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005264280.3 → XP_005264337.1  hexokinase-2 isoform X1

    UniProtKB/TrEMBL
    A8K2U2
    Conserved Domains (3) summary
    PTZ00107
    Location:12 → 460
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:21 → 219
    Hexokinase_1; Hexokinase
    pfam03727
    Location:694 → 928
    Hexokinase_2; Hexokinase

  2. XM_011532807.3 → XP_011531109.1  hexokinase-2 isoform X3

    UniProtKB/TrEMBL
    A8K2U2
    Conserved Domains (3) summary
    PTZ00107
    Location:430 → 897
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:439 → 656
    Hexokinase_1; Hexokinase
    pfam03727
    Location:662 → 896
    Hexokinase_2; Hexokinase

  3. XM_017003945.3 → XP_016859434.1  hexokinase-2 isoform X4

    UniProtKB/TrEMBL
    A8K2U2

  4. XM_047444084.1 → XP_047300040.1  hexokinase-2 isoform X2

    UniProtKB/TrEMBL
    Q68E10

  5. XM_047444085.1 → XP_047300041.1  hexokinase-2 isoform X2

    UniProtKB/TrEMBL
    Q68E10

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    74842983..74902233
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341640.1 → XP_054197615.1  hexokinase-2 isoform X1

    UniProtKB/TrEMBL
    A8K2U2

  2. XM_054341642.1 → XP_054197617.1  hexokinase-2 isoform X3

    UniProtKB/TrEMBL
    A8K2U2

  3. XM_054341643.1 → XP_054197618.1  hexokinase-2 isoform X4

    UniProtKB/TrEMBL
    A8K2U2

  4. XM_054341641.1 → XP_054197616.1  hexokinase-2 isoform X2

    UniProtKB/TrEMBL
    Q68E10
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P52789.2 GenPept UniProtKB/Swiss-Prot:P52789

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