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Aliases for HK2 Gene

Aliases for HK2 Gene

  • Hexokinase 2 2 3 5
  • Muscle Form Hexokinase 3 4
  • Hexokinase Type II 3 4
  • HK II 3 4
  • Hexokinase-2, Muscle 3
  • Hexokinase-2 3
  • EC 4
  • HKII 3
  • HXK2 3

External Ids for HK2 Gene

Previous GeneCards Identifiers for HK2 Gene

  • GC02P075198
  • GC02P075018
  • GC02P075035
  • GC02P075034
  • GC02P074971
  • GC02P075059

Summaries for HK2 Gene

Entrez Gene Summary for HK2 Gene

  • 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]

GeneCards Summary for HK2 Gene

HK2 (Hexokinase 2) is a Protein Coding gene. Diseases associated with HK2 include Pediatric Osteosarcoma and Chondroblastoma. Among its related pathways are Transcription_CREM signaling in testis and Central carbon metabolism in cancer. Gene Ontology (GO) annotations related to this gene include phosphotransferase activity, alcohol group as acceptor and fructokinase activity. An important paralog of this gene is HK1.

Tocris Summary for HK2 Gene

  • Hexokinases catalyze the first essential step of glucose metabolism, the conversion of the substrate glucose into glucose-6-phosphate. This phosphorylation event directly couples extramitochondrial glycolysis to intramitochondrial oxidative phosphorylation.

Gene Wiki entry for HK2 Gene

Additional gene information for HK2 Gene

No data available for CIViC summary , UniProtKB/Swiss-Prot , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HK2 Gene

Genomics for HK2 Gene

GeneHancer (GH) Regulatory Elements for HK2 Gene

Promoters and enhancers for HK2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J074831 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 665.1 +2.3 2257 6.7 HDGF PKNOX1 CLOCK SMAD1 FOXA2 ARID4B SIN3A FEZF1 DMAP1 SLC30A9 HK2 ENSG00000272711 GC02M074813 GC02M074833 GC02P074837 PIR31548 KRT18P26 ENSG00000230477 WBP1 BOLA3-AS1
GH02J074872 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 49.8 +41.8 41773 4.5 SCRT1 MEIS2 CTCF ZNF654 SMAD1 HLF TRIM22 REST CEBPG RAD21 HK2 M1AP SEMA4F MTHFD2 LBX2 GC02P074877 GC02M074860
GH02J074842 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 40.6 +14.9 14949 10 FOXA2 ZFP64 ARID4B NEUROD1 SIN3A ETS1 ATF7 FOS RUNX3 DEK HK2 SEMA4F M1AP ENSG00000236209 LINC01293 LBX2 GC02M074813 GC02M074860
GH02J074714 Enhancer 1.2 Ensembl ENCODE 11.8 -117.2 -117248 1.6 PKNOX1 ATF1 ARID4B SIN3A DMAP1 ZNF2 ZNF48 SLC30A9 GLIS2 ARID2 LOC102724497 GC02P074717 INO80B WBP1 GCFC2 DUSP11 HK2 SEMA4F M1AP PCGF1
GH02J074777 Enhancer 1 Ensembl ENCODE 12.4 -54.2 -54204 1.8 FOXA2 ARNT RB1 ZFP64 ARID4B SIN3A YBX1 BMI1 RAD21 ZNF48 LOC102724482 HK2 RPS28P5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HK2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HK2 gene promoter:
  • Meis-1
  • HOXA9B
  • HOXA9
  • Meis-1a
  • Bach2
  • Sox5
  • AML1a
  • HOXA3
  • Evi-1
  • Zic1

Genomic Locations for HK2 Gene

Genomic Locations for HK2 Gene
60,705 bases
Plus strand
60,705 bases
Plus strand

Genomic View for HK2 Gene

Genes around HK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HK2 Gene

Proteins for HK2 Gene

  • Protein details for HK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • D6W5J2
    • Q8WU87
    • Q9UN82

    Protein attributes for HK2 Gene

    917 amino acids
    Molecular mass:
    102380 Da
    Quaternary structure:
    • Monomer (By similarity). Interacts with TIGAR; the interaction increases hexokinase HK2 activity in a hypoxia- and HIF1A-dependent manner (PubMed:23185017).
    • In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).

    Three dimensional structures from OCA and Proteopedia for HK2 Gene

neXtProt entry for HK2 Gene

Post-translational modifications for HK2 Gene

  • Ubiquitination at Lys899, isoforms=488, isoforms=323, isoforms=173, Lys62, and Lys41
  • Modification sites at PhosphoSitePlus

Other Protein References for HK2 Gene

No data available for DME Specific Peptides for HK2 Gene

Domains & Families for HK2 Gene

Gene Families for HK2 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for HK2 Gene

Suggested Antigen Peptide Sequences for HK2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • The N- and C-terminal halves of this hexokinase show extensive sequence similarity to each other. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. Each domain can bind a single glucose and Gluc-6-P molecule.
  • Belongs to the hexokinase family.
  • The N- and C-terminal halves of this hexokinase show extensive sequence similarity to each other. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. Each domain can bind a single glucose and Gluc-6-P molecule.
  • Belongs to the hexokinase family.
genes like me logo Genes that share domains with HK2: view

Function for HK2 Gene

Molecular function for HK2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + D-hexose = ADP + D-hexose 6-phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Hexokinase is an allosteric enzyme inhibited by its product Glc-6-P.
GENATLAS Biochemistry:
hexokinase 2,108kDa,muscle and fat tissues,glycolysis,gluconeogenesis,energy pathways

Enzyme Numbers (IUBMB) for HK2 Gene

Phenotypes From GWAS Catalog for HK2 Gene

Gene Ontology (GO) - Molecular Function for HK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004340 glucokinase activity TAS --
GO:0004396 hexokinase activity IEA,TAS 9278438
GO:0005515 protein binding IPI 16189514
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with HK2: view
genes like me logo Genes that share phenotypes with HK2: view

Animal Models for HK2 Gene

MGI Knock Outs for HK2:
  • Hk2 Hk2<tm1Laak>

Animal Model Products

Clone Products

  • Addgene plasmids for HK2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HK2 Gene

Localization for HK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HK2 Gene

Mitochondrion outer membrane. Note=Its hydrophobic N-terminal sequence may be involved in membrane binding. {ECO:0000250}.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HK2 gene
Compartment Confidence
mitochondrion 5
cytosol 5
nucleus 2
plasma membrane 1
extracellular 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for HK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005739 mitochondrion IEA --
GO:0005741 mitochondrial outer membrane IDA 18350175
GO:0005829 cytosol IBA,TAS --
GO:0016020 membrane HDA,IEA 19946888
genes like me logo Genes that share ontologies with HK2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HK2 Gene

Pathways & Interactions for HK2 Gene

genes like me logo Genes that share pathways with HK2: view

UniProtKB/Swiss-Prot P52789-HXK2_HUMAN

  • Pathway: Carbohydrate metabolism; hexose metabolism.

Gene Ontology (GO) - Biological Process for HK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001678 cellular glucose homeostasis IEA,IBA --
GO:0002931 response to ischemia IEA --
GO:0005975 carbohydrate metabolic process IEA --
GO:0006006 glucose metabolic process IEA --
GO:0006096 glycolytic process IEA,TAS 23962723
genes like me logo Genes that share ontologies with HK2: view

No data available for SIGNOR curated interactions for HK2 Gene

Drugs & Compounds for HK2 Gene

(27) Drugs for HK2 Gene - From: HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
D-glucose Approved, Vet_approved Pharma 0
Galactose Approved, Investigational Pharma 0
Sorbitol Approved Pharma 41
Glucosamine Approved, Investigational Nutra 211
Glucose 6-phosphate Experimental Pharma 0

(24) Additional Compounds for HK2 Gene - From: HMDB, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
  • alpha-D-GLC
  • alpha-Dextrose
  • a-D-GLC
  • α-D-GLC
  • a-D-Glucose
Beta-D-Fructose 6-phosphate
  • 6-O-phosphono-beta-D-Fructofuranose
  • FRUCTOSE-6-phosphATE
  • 6-O-phosphono-b-D-Fructofuranose
  • 6-O-phosphono-β-D-fructofuranose
  • b-D-Fructose 6-phosphate
  • 2'-Deoxyadenosine-5'-diphosphate
  • Deoxyadenosine diphosphate
  • D-lyxo-2-Hexulose
  • D-lyxo-Hex-2-ulose
  • D-Tag
  • lyxo-2-Hexulose
  • lyxo-Hexulose

(4) Tocris Compounds for HK2 Gene

Compound Action Cas Number
2-Deoxy-D-glucose Non-metabolizable glucose analog; hexokinase substrate 154-17-6
AM 2394 Potent glucokinase activator; orally bioavailable 1442684-77-6
GKA 50 Glucokinase activator 851884-87-2
Lonidamine Mitochondrial hexokinase inhibitor 50264-69-2
genes like me logo Genes that share compounds with HK2: view

Drug Products

Transcripts for HK2 Gene

mRNA/cDNA for HK2 Gene

Unigene Clusters for HK2 Gene

Hexokinase 2:
Representative Sequences:

Clone Products

  • Addgene plasmids for HK2

Alternative Splicing Database (ASD) splice patterns (SP) for HK2 Gene

No ASD Table

Relevant External Links for HK2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HK2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HK2 Gene

This gene is overexpressed in Whole Blood (x7.0), Muscle - Skeletal (x4.9), and Colon - Transverse (x4.0).

Protein differential expression in normal tissues from HIPED for HK2 Gene

This gene is overexpressed in Brain (14.0), Retina (13.2), Bone (7.6), and Testis (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HK2 Gene

NURSA nuclear receptor signaling pathways regulating expression of HK2 Gene:


SOURCE GeneReport for Unigene cluster for HK2 Gene:


mRNA Expression by UniProt/SwissProt for HK2 Gene:

Tissue specificity: Predominant hexokinase isozyme expressed in insulin-responsive tissues such as skeletal muscle.

Evidence on tissue expression from TISSUES for HK2 Gene

  • Muscle(4.5)
  • Blood(4.4)
  • Eye(2.5)
  • Heart(2.5)
  • Intestine(2.3)
  • Nervous system(2.3)
  • Liver(2.2)
  • Lung(2.1)
genes like me logo Genes that share expression patterns with HK2: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for HK2 Gene

Orthologs for HK2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HK2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HK2 34 33
  • 99.49 (n)
(Monodelphis domestica)
Mammalia HK2 34
  • 93 (a)
(Bos Taurus)
Mammalia HK2 34 33
  • 90.44 (n)
(Canis familiaris)
Mammalia HK2 34 33
  • 90.1 (n)
(Mus musculus)
Mammalia Hk2 16 34 33
  • 87.28 (n)
(Rattus norvegicus)
Mammalia Hk2 33
  • 87.2 (n)
(Ornithorhynchus anatinus)
Mammalia HK2 34
  • 67 (a)
(Gallus gallus)
Aves HK2 34 33
  • 80.28 (n)
(Anolis carolinensis)
Reptilia HK2 34
  • 82 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100485269 33
  • 75.62 (n)
(Danio rerio)
Actinopterygii hk2 34 33
  • 72.93 (n)
Dr.10553 33
fruit fly
(Drosophila melanogaster)
Insecta Hex-C 34 35
  • 44 (a)
Hex-A 34 35
  • 42 (a)
Hex-t2 34 35
  • 41 (a)
Hex-t1 35
  • 30 (a)
(Caenorhabditis elegans)
Secernentea F14B4.2 34 35 33
  • 54.12 (n)
H25P06.1 35
  • 39 (a)
Y77E11A.1 35
  • 34 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GLK1 34
  • 34 (a)
HXK1 34
  • 34 (a)
HXK2 34
  • 32 (a)
EMI2 34
  • 32 (a)
(Oryza sativa)
Liliopsida Os01g0190400 33
  • 47.94 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.11095 34
  • 50 (a)
Species where no ortholog for HK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for HK2 Gene

Gene Tree for HK2 (if available)
Gene Tree for HK2 (if available)
Evolutionary constrained regions (ECRs) for HK2: view image

Paralogs for HK2 Gene

Paralogs for HK2 Gene

(5) SIMAP similar genes for HK2 Gene using alignment to 4 proteins:

  • E9PB90_HUMAN
  • Q53QX9_HUMAN
  • Q53SG7_HUMAN Pseudogenes for HK2 Gene

genes like me logo Genes that share paralogs with HK2: view

Variants for HK2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HK2 Gene

Although found in NIDDM patients, genetic variations of HK2 do not contribute to the disease (PubMed:7883122, PubMed:7883123).

Sequence variations from dbSNP and Humsavar for HK2 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1000000977 -- 74,845,386(+) C/T intron_variant
rs1000034228 -- 74,892,881(+) A/G 3_prime_UTR_variant
rs1000036793 -- 74,888,176(+) A/T intron_variant
rs1000132043 -- 74,870,825(+) T/C intron_variant
rs1000145026 -- 74,888,345(+) T/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for HK2 Gene

Variant ID Type Subtype PubMed ID
dgv3871n100 CNV gain 25217958
esv2659874 CNV deletion 23128226
esv2677814 CNV deletion 23128226
esv2751900 CNV gain 17911159
esv2760619 CNV loss 21179565
esv3591289 CNV loss 21293372
esv3591291 CNV loss 21293372
nsv1001495 CNV gain 25217958
nsv1109262 CNV deletion 24896259
nsv1138786 CNV deletion 24896259
nsv518615 CNV gain 19592680
nsv519007 CNV loss 19592680
nsv582217 CNV gain 21841781
nsv829465 CNV loss 20364138
nsv998325 CNV gain 25217958

Variation tolerance for HK2 Gene

Residual Variation Intolerance Score: 37.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.44; 85.68% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HK2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

Disorders for HK2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for HK2 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
pediatric osteosarcoma
  • childhood osteosarcoma
  • chondroblastoma of bone
diabetes mellitus
  • diabetes
diabetes mellitus, noninsulin-dependent
  • niddm
- elite association - COSMIC cancer census association via MalaCards
Search HK2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HK2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HK2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HK2 Gene

Publications for HK2 Gene

  1. Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity. (PMID: 7883123) Echwald SM … Pedersen O (Diabetes 1995) 3 4 22 44 58
  2. Amino acid substitutions in hexokinase II among patients with NIDDM. (PMID: 7883120) Laakso M … Deeb SS (Diabetes 1995) 3 4 22 44 58
  3. Analysis of the hexokinase II gene in subjects with insulin resistance and NIDDM and detection of a Gln142-->His substitution. (PMID: 7883122) Vidal-Puig A … Moller DE (Diabetes 1995) 3 4 22 44 58
  4. Human hexokinase II gene: exon-intron organization, mutation screening in NIDDM, and its relationship to muscle hexokinase activity. (PMID: 8786021) Lehto M … Groop L (Diabetologia 1995) 3 4 22 58
  5. Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines. (PMID: 7518342) Shinohara Y … Terada H (Cancer letters 1994) 3 4 22 58

Products for HK2 Gene

  • Addgene plasmids for HK2

Sources for HK2 Gene

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