HK2

protein-coding

hexokinase 2

Gene 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]

MANE transcript

NM_000189.5

Inheritance

—

ClinVar variants

U:132B:25

Top phenotype

HK2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:74,834,127-74,893,359

External References & Databases

Ensembl (ENSG00000159399)

Transcript & Mutation Effects

hg38 • Region Span ~59.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HK2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 124

HK2-related disorderTotal: 19

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000189.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	14 clinvar	3 clinvar	19
missense			124 clinvar	6 clinvar	2 clinvar	132
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	132	20	5	157

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000189.5	RefSeq	NP_000180.2	18	MANE Select
ENST00000290573.7	Ensembl	ENSP00000290573.2	18	MANE Select
NM_001371525.1	RefSeq	NP_001358454.1	17	Standard
ENST00000409174.1	Ensembl	ENSP00000387140.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycolysis / Gluconeogenesis - Homo sapiens (human)
Fructose and mannose metabolism - Homo sapiens (human)
Central carbon metabolism in cancer - Homo sapiens (human)
Type II diabetes mellitus - Homo sapiens (human)
HIF-1 signaling pathway - Homo sapiens (human)

Biological Process

response to hypoxia
cellular glucose homeostasis
response to ischemia
glycolytic process
lactation

Molecular Function

glucokinase activity
hexokinase activity
protein binding
ATP binding
glucose binding

Cellular Component

mitochondrial outer membrane
cytosol
plasma membrane
membrane
sarcoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290573
Coding exons: 18
Length: 59379
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	477	553	0.862	0.0000382	6040
Missense (PolyPhen)		151	221.87	0.68059		2578
Synonymous	-1.32	243	218	1.11	0.0000155	1801
Loss of Function	4.11	12	40.1	0.299	0.00000234	469

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.458

Intolerance Scores

LoFtool: 0.0828
RVIS EVS: -0.95
RVIS percentile EVS: 9.38

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium