GK

glycerol kinase, the group of Glycerol kinases

Basic information

Region (hg38): X:30653358-30731462

Links

ENSG00000198814 ∙ NCBI:2710 ∙ OMIM:300474 ∙ HGNC:4289 ∙ Uniprot:P32189 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• inborn glycerol kinase deficiency (Definitive), mode of inheritance: XLR
• inborn glycerol kinase deficiency (Definitive), mode of inheritance: AR
• inborn glycerol kinase deficiency (Strong), mode of inheritance: XL
• inborn glycerol kinase deficiency (Definitive), mode of inheritance: XL
• inborn glycerol kinase deficiency (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycerol kinase deficiency	XL	Biochemical	Specific dietary measures (eg, fat/glycerol-restricted diet) can be beneficial	Biochemical; Neurologic	6325658; 8651297; 9719371; 10736265; 11032329; 18607276; 21542762; 23009783

ClinVar

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

• not provided (5 variants)
• Inborn glycerol kinase deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GK 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	5	7
missense			21	1		22
nonsense	2	2				4
start loss						0
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)	2	2				4
splice region				1		1
non coding	1		1	3	25	30
Total	7	5	22	6	30

Highest pathogenic variant AF is 0.000355

Variants in GK

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

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

Position	Type	Phenotype	Significance	ClinVar
X-30653592-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2023)
X-30653592-G-C		See cases	Uncertain significance (Apr 13, 2023)
X-30653624-G-A		GK-related disorder	Likely benign (Mar 02, 2019)
X-30653779-G-C			Benign (May 12, 2021)
X-30665521-C-A		GK-related disorder	Likely pathogenic (Sep 08, 2023)
X-30665538-C-T		Inborn glycerol kinase deficiency	Uncertain significance (Mar 01, 2022)
X-30665578-G-A		Inborn genetic diseases	Uncertain significance (Jul 29, 2023)
X-30665585-G-C		Inborn genetic diseases • Inborn glycerol kinase deficiency	Likely pathogenic (Jan 17, 2019)
X-30667920-A-C			Benign (May 21, 2021)
X-30668024-G-A		Inborn genetic diseases	Benign (Oct 29, 2019)
X-30668045-T-C		GK-related disorder	Benign (Apr 14, 2020)
X-30668056-A-C		Inborn glycerol kinase deficiency	Uncertain significance (Aug 06, 2021)
X-30668094-A-C		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
X-30668097-A-G		Inborn genetic diseases • GK-related disorder	Conflicting classifications of pathogenicity (Aug 30, 2023)
X-30668107-C-T			Uncertain significance (Apr 17, 2019)
X-30668120-T-C			Pathogenic (Jun 02, 2015)
X-30669373-G-A		Inborn glycerol kinase deficiency	Pathogenic (May 04, 2022)
X-30669375-G-A		GK-related disorder	Likely benign (Mar 02, 2023)
X-30670451-G-T			Benign (Jun 19, 2021)
X-30670598-ATT-A			Benign (Jun 20, 2021)
X-30691149-A-G		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
X-30691154-TGA-T			Pathogenic (Jun 12, 2023)
X-30691157-G-A			Benign (Jul 31, 2018)
X-30691166-TA-T			Likely pathogenic (Jun 01, 2020)
X-30691167-A-G			Uncertain significance (Jan 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GK	protein_coding	protein_coding	ENST00000378943	20	77250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0106	125687	0	3	125690	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.19	81	211	0.383	0.0000156	3616
Missense in Polyphen		13	75.463	0.17227		1380
Synonymous	0.776	64	72.4	0.884	0.00000565	1040
Loss of Function	4.27	3	26.9	0.112	0.00000199	445

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000738	0.0000738
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000125	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism.
• Pathway: Glycerolipid metabolism - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Familial lipoprotein lipase deficiency;Glycerolipid Metabolism;Glycerol Kinase Deficiency;D-glyceric acidura;Fatty Acid Beta Oxidation;Type II diabetes mellitus;Triacylglyceride Synthesis;Metabolism of lipids;Metabolism;CDP-diacylglycerol biosynthesis;Glycerophospholipid metabolism;Triglyceride biosynthesis;Triglyceride metabolism;glycerol degradation (Consensus)

Recessive Scores

• pRec: 0.444

Intolerance Scores

• loftool: 0.121
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.675
• ghis: 0.616

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.151

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gk
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: glycerol metabolic process;triglyceride metabolic process;phosphorylation;triglyceride biosynthetic process;glycerol catabolic process;glycerol-3-phosphate biosynthetic process
• Cellular component: cytoplasm;mitochondrion;mitochondrial outer membrane;cytosol;extracellular exosome
• Molecular function: glycerol kinase activity;protein binding;ATP binding