KHK

ketohexokinase

Basic information

Region (hg38): 2:27086771-27100762

Links

ENSG00000138030 ∙ NCBI:3795 ∙ OMIM:614058 ∙ HGNC:6315 ∙ Uniprot:P50053 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• essential fructosuria (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fructosuria, essential	AR	General	The clinical relevance of the condition is unclear	Biochemical	13759156; 14063525; 6268573; 7816517; 7833921

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KHK gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KHK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	2	2	9
missense			29	3	1	33
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1	1	3
non coding			24	3	17	44
Total	0	0	60	8	20

Variants in KHK

This is a list of pathogenic ClinVar variants found in the KHK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-27086791-A-C		Essential fructosuria	Benign (Jan 13, 2018)
2-27086811-T-G		Essential fructosuria	Benign (Jan 12, 2018)
2-27086816-C-A		Essential fructosuria	Benign (Jan 13, 2018)
2-27086881-T-A		Essential fructosuria	Uncertain significance (Jan 13, 2018)
2-27086936-C-T		Essential fructosuria	Benign (Jan 12, 2018)
2-27087015-G-A		Essential fructosuria	Benign (Jan 12, 2018)
2-27087120-G-A		Essential fructosuria	Uncertain significance (Jan 13, 2018)
2-27087163-G-A		Essential fructosuria	Uncertain significance (Jan 12, 2018)
2-27087245-T-G		Essential fructosuria	Uncertain significance (Jan 13, 2018)
2-27087274-G-A		Essential fructosuria	Uncertain significance (Jan 12, 2018)
2-27087278-C-T		Essential fructosuria • KHK-related disorder	Conflicting classifications of pathogenicity (Feb 28, 2019)
2-27087307-C-T		Essential fructosuria	Uncertain significance (Jan 12, 2018)
2-27087347-A-T		not specified	Uncertain significance (Oct 04, 2022)
2-27092340-C-A		Essential fructosuria	Uncertain significance (Jan 13, 2018)
2-27092343-A-G		not specified	Uncertain significance (Oct 03, 2022)
2-27092351-C-T		Essential fructosuria	Uncertain significance (Feb 14, 2022)
2-27092357-G-A		Essential fructosuria	Pathogenic (Sep 01, 1994)
2-27092366-G-A		Essential fructosuria	Pathogenic (Sep 01, 1994)
2-27092383-C-T		KHK-related disorder	Likely benign (Feb 28, 2019)
2-27092384-G-A		Essential fructosuria	Benign (Jan 13, 2018)
2-27092398-C-T		Essential fructosuria	Benign (Jan 13, 2018)
2-27092402-G-A		not specified	Uncertain significance (Sep 14, 2022)
2-27092428-G-A		Essential fructosuria	Likely benign (Jan 12, 2018)
2-27094466-C-T		Essential fructosuria	Uncertain significance (Jan 13, 2018)
2-27094472-A-G		Essential fructosuria	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KHK	protein_coding	protein_coding	ENST00000260599	8	14026

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.07e-9	0.137	125662	0	86	125748	0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.451	193	176	1.10	0.0000118	1927
Missense in Polyphen		72	68.539	1.0505		722
Synonymous	-0.898	86	76.0	1.13	0.00000574	601
Loss of Function	0.267	14	15.1	0.926	7.63e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000532	0.000437
Ashkenazi Jewish	0.00159	0.00159
East Asian	0.000230	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000230	0.000217
South Asian	0.000817	0.000817
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate. {ECO:0000269|PubMed:12941785}.
• Pathway: Fructose and mannose metabolism - Homo sapiens (human);Uric Acid-Lowering Drugs Pathway, Pharmacodynamics;Fructose intolerance, hereditary;Fructose and Mannose Degradation;Fructosuria;Polyol Pathway;Fructose metabolism;Metabolism of carbohydrates;Fructose Mannose metabolism;Metabolism;Fructose catabolism;sucrose degradation (Consensus)

Recessive Scores

• pRec: 0.249

Intolerance Scores

• loftool: 0.553
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.49

Haploinsufficiency Scores

• pHI: 0.115
• hipred: N
• hipred_score: 0.197
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Khk

Gene ontology

• Biological process: fructose metabolic process;response to sucrose;response to glucose;response to fructose;response to zinc ion;response to insulin;carbohydrate phosphorylation;fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate;regulation of glycogen metabolic process
• Cellular component: cytoplasm;cytosol;extracellular exosome
• Molecular function: ketohexokinase activity;protein binding;ATP binding;carbohydrate kinase activity