HK3

protein-coding

hexokinase 3

Gene summary

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 3. Similar to hexokinases 1 and 2, this allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009]

MANE transcript

NM_002115.3

Inheritance

—

ClinVar variants

U:200B:23

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr5:176,880,869-176,899,346

External References & Databases

Ensembl (ENSG00000160883)

Transcript & Mutation Effects

hg38 • Region Span ~18.5 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 HK3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 202

not providedTotal: 14

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002115.3. 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			5 clinvar	5 clinvar	2 clinvar	12
missense			194 clinvar	14 clinvar	2 clinvar	210
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	200	19	4	223

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002115.3	RefSeq	NP_002106.2	18	MANE Select
ENST00000292432.10	Ensembl	ENSP00000292432.5	18	MANE Select
ENST00000504910.1	Ensembl	ENSP00000427000.1	2	Standard
ENST00000509717.5	Ensembl	ENSP00000422169.1	2	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

cellular glucose homeostasis
glycolytic process
neutrophil degranulation
carbohydrate phosphorylation
glucose 6-phosphate metabolic process

Molecular Function

glucokinase activity
hexokinase activity
ATP binding
glucose binding
fructokinase activity

Cellular Component

extracellular region
cytosol
secretory granule lumen
ficolin-1-rich granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000292432
Coding exons: 18
Length: 18464
Individuals with no LoFs: 125551
Homozygous LoFs: 1
Heterozygous LoFs: 196
Defined: 125748
p: 0.000784

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0277	593	595	0.997	0.0000389	5897
Missense (PolyPhen)		269	271.82	0.98964		2795
Synonymous	-0.680	267	253	1.05	0.0000169	1995
Loss of Function	0.681	37	41.7	0.886	0.00000214	423

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.00067	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0017	0.0017	notable
Finnish	0.00011	0.000092	rare
European (Non-Finnish)	0.00081	0.00081	rare
South Asian	0.00095	0.00091	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.188

Intolerance Scores

LoFtool: 0.0604
RVIS EVS: -0.56
RVIS percentile EVS: 19.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.713

Gene Damage Prediction

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