HK1 hexokinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HK1provided by HGNC
Official Full Name: hexokinase 1provided by HGNC
Primary source: HGNC:HGNC:4922
See related: Ensembl:ENSG00000156515 MIM:142600; AllianceGenome:HGNC:4922
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: HK; HKD; HKI; HXK1; NMSR; RP79; HMSNR; CNSHA5; HK1-ta; HK1-tb; HK1-tc; NEDVIBA; hexokinase
Summary: Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]
Expression: Ubiquitous expression in heart (RPKM 41.2), esophagus (RPKM 41.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q22.1

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (69270000..69401882)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (70138041..70269925)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (71029756..71161638)

Chromosome 10 - NC_000010.11 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?

MiR-34a-HK1 signal axis retards bone marrow mesenchymal stem cell senescence via ameliorating glycolytic metabolism.
Title: MiR-34a-HK1 signal axis retards bone marrow mesenchymal stem cell senescence via ameliorating glycolytic metabolism.
Hemokinin-1 is a mediator of chronic restraint stress-induced pain.
Title: Hemokinin-1 is a mediator of chronic restraint stress-induced pain.
Expanding the Molecular Spectrum of HK1-Related Charcot-Marie-Tooth Disease, Type 4G; the First Report in Iran.
Title: Expanding the Molecular Spectrum of HK1-Related Charcot-Marie-Tooth Disease, Type 4G; the First Report in Iran.
Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.
Title: Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.
DDX24 promotes tumor progression by mediating hexokinase-1 induced glycolysis in gastric cancer.
Title: DDX24 promotes tumor progression by mediating hexokinase-1 induced glycolysis in gastric cancer.
Proteomic analyses identify HK1 and ATP5A to be overexpressed in distant metastases of lung adenocarcinomas compared to matched primary tumors.
Title: Proteomic analyses identify HK1 and ATP5A to be overexpressed in distant metastases of lung adenocarcinomas compared to matched primary tumors.
Intermittent Hypoxia Promotes TAM-Induced Glycolysis in Laryngeal Cancer Cells via Regulation of HK1 Expression through Activation of ZBTB10.
Title: Intermittent Hypoxia Promotes TAM-Induced Glycolysis in Laryngeal Cancer Cells via Regulation of HK1 Expression through Activation of ZBTB10.
Targeting hexokinase 1 alleviates NLRP3-mediated inflammation in apical periodontitis: A laboratory investigation.
Title: Targeting hexokinase 1 alleviates NLRP3-mediated inflammation in apical periodontitis: A laboratory investigation.
Expanding the neurodevelopmental phenotype associated with HK1 de novo heterozygous missense variants.
Title: Expanding the neurodevelopmental phenotype associated with HK1 de novo heterozygous missense variants.
Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism.
Title: Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism.

Submit: New GeneRIF Correction See all GeneRIFs (72)

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
Charcot-Marie-Tooth disease type 4G MedGen: C1854449 OMIM: 605285 GeneReviews: Not available	Compare labs
Hemolytic anemia due to hexokinase deficiency MedGen: C3150343 OMIM: 235700 GeneReviews: Not available	Compare labs
Neurodevelopmental disorder with visual defects and brain anomalies MedGen: C5231404 OMIM: 618547 GeneReviews: Not available	Compare labs
Retinitis pigmentosa 79 MedGen: C4479526 OMIM: 617460 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Common variants at 10 genomic loci influence hemoglobin A&#x000e2;&#x00082;&#x00081;(C) levels via glycemic and nonglycemic pathways. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seventy-five genetic loci influencing the human red blood cell. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	HIV-1 modulates subcellular localization of HK1 favoring increased association of HK1 with mitochondria, and HIV-1 protein Vpr induces accumulation of HK1 from the cytoplasm to the mitochondria	PubMed
	vpr	The expression of hexokinase 1 (HK1) is upregulated in HIV-1 infected PBMCs and monocyte-like cell line U1, and HIV-1 Vpr transduced U937 cell derived macrophages	PubMed
	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of hexokinase 1 (HK1) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M75126 (e-PCR)
- UniSTS:72709

STS-W37533 (e-PCR)
- UniSTS:81180

RH80106 (e-PCR)
- UniSTS:85846

SHGC-35892 (e-PCR)
- UniSTS:27479

SHGC-153484 (e-PCR)
- UniSTS:177776

GDB:181720 (e-PCR)
- UniSTS:155332

HK1 (e-PCR)
- UniSTS:468459

HK1__6571 (e-PCR)
- UniSTS:468459

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 fructokinase activity	IBA Inferred from Biological aspect of Ancestor 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	ISS Inferred from Sequence or Structural Similarity more info
enables glucokinase activity	TAS Traceable Author Statement more info
enables glucosamine kinase activity	IEA Inferred from Electronic Annotation more info
enables hexokinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables mannokinase activity	EXP Inferred from Experiment more info	PubMed
enables mannokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables mannokinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables peptidoglycan binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in GDP-mannose biosynthetic process	TAS Traceable Author Statement more info
involved_in GDP-mannose biosynthetic process from glucose	IEA Inferred from Electronic Annotation more info
involved_in GDP-mannose biosynthetic process from mannose	IEA Inferred from Electronic Annotation more info
involved_in canonical glycolysis	TAS Traceable Author Statement more info
involved_in carbohydrate phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of protein localization to mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
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	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycolytic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in intracellular glucose homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in maintenance of protein location in mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mannose metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cytokine production involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-1 beta production	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane raft	IEA Inferred from Electronic Annotation more info
located_in mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	HTP 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

General protein information

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Preferred Names: hexokinase-1

Names: Neuropathy, hereditary motor and sensory, Russe type; brain form hexokinase; glycolytic enzyme; hexokinase IR; hexokinase type I; hexokinase-A

NP_000179.2

EC 2.7.1.1

NP_001309293.1

EC 2.7.1.1

NP_001309294.1

EC 2.7.1.1

NP_001309295.1

EC 2.7.1.1

NP_001309296.1

EC 2.7.1.1

NP_001345192.1

EC 2.7.1.1

NP_277031.1

EC 2.7.1.1

NP_277032.1

EC 2.7.1.1

NP_277033.1

EC 2.7.1.1

NP_277035.2

EC 2.7.1.1

XP_024303737.1

EC 2.7.1.1

XP_047281092.1

EC 2.7.1.1

XP_047281093.1

EC 2.7.1.1

XP_047281095.1

EC 2.7.1.1

XP_054221661.1

EC 2.7.1.1

XP_054221662.1

EC 2.7.1.1

XP_054221663.1

EC 2.7.1.1

XP_054221664.1

EC 2.7.1.1

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_012077.1 RefSeqGene

Range

5001..136883

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_365

mRNA and Protein(s)

NM_000188.3 → NP_000179.2 hexokinase-1 isoform HKI

See identical proteins and their annotated locations for NP_000179.2

Status: REVIEWED

Description

Transcript Variant: This variant (1), HKI, encodes the ubiquitously expressed isoform. Its 5' end includes an exon which is unique to this transcript and which encodes a distinct N-terminus that contains the porin binding domain (PBD). The porin binding domain mediates association with the mitochondrial membrane.

Source sequence(s)

AB209526, AK128226, AK292012, BC008730

Consensus CDS

CCDS7292.1

UniProtKB/Swiss-Prot

E9PCK0, O43443, O43444, O75574, P19367, Q5VTC3, Q96HC8, Q9NNZ4, Q9NNZ5

UniProtKB/TrEMBL

A8K7J7

Related

ENSP00000352398.6, ENST00000359426.7

Conserved Domains (3) summary

PTZ00107
Location:12 → 460

PTZ00107; hexokinase; Provisional

pfam00349
Location:469 → 667

Hexokinase_1

pfam03727
Location:673 → 907

Hexokinase_2
NM_001322364.2 → NP_001309293.1 hexokinase-1 isoform HKI-ta/tb

Status: REVIEWED

Description

Transcript Variant: Variants 3, 4, 6 and 10 all encode isoform HKI-ta/tb, which has a unique N-terminus. Isoform HKI-ta/tb lacks the porin binding domain (PBD) required for association with the mitochondrial membrane.

Source sequence(s)

AC016821, AL596223

Consensus CDS

CCDS7289.1

UniProtKB/TrEMBL

B3KXY9

Conserved Domains (3) summary

pfam00349
Location:473 → 671

Hexokinase_1; Hexokinase

pfam03727
Location:677 → 911

Hexokinase_2; Hexokinase

cl27242
Location:16 → 464

Hexokinase_2; Hexokinase
NM_001322365.2 → NP_001309294.1 hexokinase-1 isoform a

Status: REVIEWED

Source sequence(s)

AC016821, AL596223

UniProtKB/TrEMBL

B3KXY9

Conserved Domains (3) summary

PTZ00107
Location:47 → 495

PTZ00107; hexokinase; Provisional

pfam00349
Location:504 → 702

Hexokinase_1; Hexokinase

pfam03727
Location:708 → 942

Hexokinase_2; Hexokinase
NM_001322366.1 → NP_001309295.1 hexokinase-1 isoform b

Status: REVIEWED

Source sequence(s)

AC016821, AL596223

Consensus CDS

CCDS91250.1

UniProtKB/TrEMBL

A0A994J753, A8K7J7

Related

ENSP00000515578.1, ENST00000703945.1

Conserved Domains (3) summary

PTZ00107
Location:1 → 432

PTZ00107; hexokinase; Provisional

pfam00349
Location:441 → 639

Hexokinase_1; Hexokinase

pfam03727
Location:645 → 879

Hexokinase_2; Hexokinase
NM_001322367.1 → NP_001309296.1 hexokinase-1 isoform c

Status: REVIEWED

Source sequence(s)

AC016821, AL596223

UniProtKB/TrEMBL

A8K7J7

Conserved Domains (3) summary

PTZ00107
Location:430 → 875

PTZ00107; hexokinase; Provisional

pfam00349
Location:437 → 635

Hexokinase_1; Hexokinase

pfam03727
Location:641 → 875

Hexokinase_2; Hexokinase
NM_001358263.1 → NP_001345192.1 hexokinase-1 isoform HKI-ta/tb

Status: REVIEWED

Description

Transcript Variant: Variants 3, 4, 6 and 10 all encode isoform HKI-ta/tb, which has a unique N-terminus. Isoform HKI-ta/tb lacks the porin binding domain (PBD) required for association with the mitochondrial membrane.

Source sequence(s)

AC016821, AL596223, BM686492

Consensus CDS

CCDS7289.1

UniProtKB/TrEMBL

B3KXY9

Related

ENSP00000494664.1, ENST00000643399.2

Conserved Domains (3) summary

pfam00349
Location:473 → 671

Hexokinase_1; Hexokinase

pfam03727
Location:677 → 911

Hexokinase_2; Hexokinase

cl27242
Location:16 → 464

Hexokinase_2; Hexokinase
NM_033496.3 → NP_277031.1 hexokinase-1 isoform HKI-R

See identical proteins and their annotated locations for NP_277031.1

Status: REVIEWED

Description

Transcript Variant: Variant 2 (HKI-R) encodes the erythroid-specific isoform. Isoform HKI-R lacks the porin binding domain (PBD), which mediates association with the mitochondrial membrane, and thus localizes to the cytoplasm. Variant 2 includes an erythroid-specific exon in the 5' end which encodes a distinct N-terminus.

Source sequence(s)

AK128226, AL596223, BC008730, BX406321

Consensus CDS

CCDS7291.1

UniProtKB/TrEMBL

A8K7J7

Related

ENSP00000298649.3, ENST00000298649.8

Conserved Domains (3) summary

PTZ00107
Location:21 → 459

PTZ00107; hexokinase; Provisional

pfam00349
Location:468 → 666

Hexokinase_1; Hexokinase

pfam03727
Location:672 → 906

Hexokinase_2; Hexokinase
NM_033497.3 → NP_277032.1 hexokinase-1 isoform HKI-ta/tb

See identical proteins and their annotated locations for NP_277032.1

Status: REVIEWED

Description

Transcript Variant: Variant 3 (HKI-ta) includes four testis-specific exons in the 5' end. Variants 3, 4, 6 and 10 all encode isoform HKI-ta/tb, which has a unique N-terminus. Isoform HKI-ta/tb lacks the porin binding domain (PBD) required for association with the mitochondrial membrane.

Source sequence(s)

AF073786, AK128226, BC008730, DB088955

Consensus CDS

CCDS7289.1

UniProtKB/TrEMBL

B3KXY9

Related

ENSP00000415949.2, ENST00000436817.6

Conserved Domains (3) summary

pfam00349
Location:473 → 671

Hexokinase_1; Hexokinase

pfam03727
Location:677 → 911

Hexokinase_2; Hexokinase

cl27242
Location:16 → 464

Hexokinase_2; Hexokinase
NM_033498.3 → NP_277033.1 hexokinase-1 isoform HKI-ta/tb

See identical proteins and their annotated locations for NP_277033.1

Status: REVIEWED

Description

Transcript Variant: Variant 4 (HKI-tb) has four testis-specific exons in the 5' end, one of which includes an additional 54 nt fragment unique to variants 4 and 5. Variants 3, 4, 6 and 10 all encode isoform HKI-ta/tb, which has a unique N-terminus. Isoform HKI-ta/tb lacks the porin binding domain (PBD) required for association with the mitochondrial membrane.

Source sequence(s)

AF073786, AK128226, BC008730, U38226

Consensus CDS

CCDS7289.1

UniProtKB/TrEMBL

B3KXY9

Conserved Domains (3) summary

pfam00349
Location:473 → 671

Hexokinase_1; Hexokinase

pfam03727
Location:677 → 911

Hexokinase_2; Hexokinase

cl27242
Location:16 → 464

Hexokinase_2; Hexokinase
NM_033500.2 → NP_277035.2 hexokinase-1 isoform HKI-td

See identical proteins and their annotated locations for NP_277035.2

Status: REVIEWED

Description

Transcript Variant: Variant 5 (HKI-td) has five testis-specific exons in the 5' end, one of which includes an additional 54 nt fragment unique to variants 4 and 5. Isoform HKI-td has a unique N-terminus and lacks the porin binding domain (PBD) required for association with the mitochondrial membrane.

Source sequence(s)

AF073786, AK128226, BC008730, U38227

UniProtKB/TrEMBL

A8K7J7

Conserved Domains (3) summary

PTZ00107
Location:10 → 448

PTZ00107; hexokinase; Provisional

pfam00349
Location:457 → 655

Hexokinase_1; Hexokinase

pfam03727
Location:661 → 895

Hexokinase_2; Hexokinase

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_000010.11 Reference GRCh38.p14 Primary Assembly

Range

69270000..69401882

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047425137.1 → XP_047281093.1 hexokinase-1 isoform X1
XM_047425136.1 → XP_047281092.1 hexokinase-1 isoform X1
XM_024447969.2 → XP_024303737.1 hexokinase-1 isoform X1

UniProtKB/TrEMBL

B3KXY9

Conserved Domains (3) summary

pfam00349
Location:473 → 671

Hexokinase_1; Hexokinase

pfam03727
Location:677 → 911

Hexokinase_2; Hexokinase

cl27242
Location:16 → 464

Hexokinase_2; Hexokinase
XM_047425139.1 → XP_047281095.1 hexokinase-1 isoform X2