HK1

hexokinase 1

Basic information

Region (hg38): 10:69269984-69401884

Links

ENSG00000156515 ∙ NCBI:3098 ∙ OMIM:142600 ∙ HGNC:4922 ∙ Uniprot:P19367 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-spherocytic hemolytic anemia due to hexokinase deficiency (Moderate), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4G (Limited), mode of inheritance: AR
• retinitis pigmentosa 79 (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with visual defects and brain anomalies (Moderate), mode of inheritance: AD
• non-spherocytic hemolytic anemia due to hexokinase deficiency (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4G (Supportive), mode of inheritance: AR
• non-spherocytic hemolytic anemia due to hexokinase deficiency (Strong), mode of inheritance: AR
• retinitis pigmentosa 79 (Strong), mode of inheritance: AD
• neurodevelopmental disorder with visual defects and brain anomalies (Strong), mode of inheritance: AD
• retinitis pigmentosa 79 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, congenital, nonspherocytic hemolytic, 5	AR	Hematologic	Individuals may manifest with severe hemolysis, and anemia may be sufficiently severe to require splenectomy	Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	6015552; 27532; 7234862; 6848140; 7655856; 12393545; 19536174; 19608687; 22978647; 25190649; 25316723; 30778173

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HK1 gene.

• not provided (9 variants)
• Neurodevelopmental disorder with visual defects and brain anomalies (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HK1 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			2	154	11	167
missense	1	11	290	4	4	310
nonsense	3	1	1			5
start loss		2				2
frameshift	5		4			9
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2	5			7
splice region			14	21	2	37
non coding			5	88	17	110
Total	9	16	310	246	32

Highest pathogenic variant AF is 0.00000657

Variants in HK1

This is a list of pathogenic ClinVar variants found in the HK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-69278684-G-A		HK1-related disorder	Likely benign (May 30, 2019)
10-69278691-G-C		Charcot-Marie-Tooth disease type 4G	not provided (-)
10-69278711-G-C		Charcot-Marie-Tooth disease type 4G • Hemolytic anemia due to hexokinase deficiency	Conflicting classifications of pathogenicity (Aug 01, 2024)
10-69280026-G-A			Conflicting classifications of pathogenicity (Dec 16, 2024)
10-69288744-A-G		Charcot-Marie-Tooth disease type 4G	Likely pathogenic (May 28, 2019)
10-69288744-A-T		Hemolytic anemia due to hexokinase deficiency	Likely pathogenic (May 04, 2022)
10-69288747-G-A		Charcot-Marie-Tooth disease type 4G	Uncertain significance (Aug 07, 2018)
10-69288762-C-T		Charcot-Marie-Tooth disease type 4G • Neurodevelopmental disorder with visual defects and brain anomalies	Pathogenic/Likely pathogenic (Nov 01, 2020)
10-69288770-G-A		HK1-related disorder	Uncertain significance (Jul 18, 2023)
10-69292286-T-A		HK1-related disorder	Likely benign (Sep 03, 2024)
10-69292304-G-A		not specified • HK1-related disorder	Uncertain significance (Mar 07, 2019)
10-69292305-T-A			Likely benign (Jul 17, 2024)
10-69292327-C-T			Benign (Nov 28, 2024)
10-69295633-G-T			Likely benign (May 05, 2022)
10-69295658-T-C		Neurodevelopmental disorder with visual defects and brain anomalies;Retinitis pigmentosa 79;Charcot-Marie-Tooth disease type 4G;Hemolytic anemia due to hexokinase deficiency • HK1-related disorder	Likely benign (Aug 01, 2024)
10-69295662-T-C			Likely benign (Feb 01, 2024)
10-69295692-AT-A		not specified	Benign (Sep 27, 2024)
10-69295692-A-AT			Benign (May 14, 2024)
10-69295692-A-ATT			Likely benign (Oct 20, 2023)
10-69295696-T-C		not specified	Benign/Likely benign (-)
10-69295703-T-C		Hemolytic anemia due to hexokinase deficiency • Charcot-Marie-Tooth disease type 4G • Neurodevelopmental disorder with visual defects and brain anomalies • Retinitis pigmentosa 79	Benign (Aug 10, 2021)
10-69300853-CA-TG		HK1-related disorder	Likely benign (Oct 11, 2023)
10-69300854-A-G		Retinitis pigmentosa 79 • Hemolytic anemia due to hexokinase deficiency • Neurodevelopmental disorder with visual defects and brain anomalies • Charcot-Marie-Tooth disease type 4G • not specified • Retinal dystrophy	Benign (Nov 29, 2024)
10-69300862-G-C		HK1-related disorder	Uncertain significance (Dec 18, 2023)
10-69300865-C-T			Benign (Nov 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HK1	protein_coding	protein_coding	ENST00000404387	19	131899

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.915	0.0854	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.23	341	555	0.614	0.0000371	6078
Missense in Polyphen		93	224.04	0.41511		2446
Synonymous	0.731	210	224	0.938	0.0000161	1814
Loss of Function	4.96	8	43.2	0.185	0.00000256	499

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000968	0.0000967
Middle Eastern	0.000217	0.000217
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Hexokinase deficiency (HK deficiency) [MIM:235700]: Rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature. {ECO:0000269|PubMed:12393545, ECO:0000269|PubMed:7655856}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neuropathy, hereditary motor and sensory, Russe type (HMSNR) [MIM:605285]: An autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy. {ECO:0000269|PubMed:19536174}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 79 (RP79) [MIM:617460]: A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP79 inheritance is autosomal dominant. {ECO:0000269|PubMed:25190649, ECO:0000269|PubMed:25316723}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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);Starch and sucrose metabolism - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Neomycin, kanamycin and gentamicin biosynthesis - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Pentose Phosphate Pathway (Erythrocyte);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;Fructose intolerance, hereditary;Galactose Metabolism;Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Fructose and Mannose Degradation;Galactosemia;Fructosuria;Salla Disease/Infantile Sialic Acid Storage Disease;Cori Cycle;Photodynamic therapy-induced HIF-1 survival signaling;fig-met-1-last-solution;Pathways in clear cell renal cell carcinoma;Glycolysis and Gluconeogenesis;Glucuronidation;Aminosugars metabolism;Metabolism of carbohydrates;Fructose Mannose metabolism;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Metabolism;Glycolysis;Fructose and mannose metabolism;GDP-glucose biosynthesis II;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Glucose metabolism;HIF-1-alpha transcription factor network;Galactose metabolism (Consensus)

Recessive Scores

• pRec: 0.802

Intolerance Scores

• loftool: 0.0552
• rvis_EVS: -1.22
• rvis_percentile_EVS: 5.64

Haploinsufficiency Scores

• pHI: 0.858
• hipred: Y
• hipred_score: 0.639
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hk1
• Phenotype: hematopoietic system phenotype; reproductive system phenotype; liver/biliary system phenotype; renal/urinary system phenotype; immune system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: cellular glucose homeostasis;positive regulation of cytokine secretion involved in immune response;glycolytic process;carbohydrate phosphorylation;positive regulation of interleukin-1 beta secretion;glucose 6-phosphate metabolic process;canonical glycolysis;establishment of protein localization to mitochondrion;maintenance of protein location in mitochondrion
• Cellular component: mitochondrion;mitochondrial outer membrane;cytosol;membrane raft
• Molecular function: glucokinase activity;hexokinase activity;protein binding;ATP binding;glucose binding;fructokinase activity;mannokinase activity;identical protein binding;peptidoglycan binding