GCKR

glucokinase regulator

Basic information

Region (hg38): 2:27496838-27523684

Links

ENSG00000084734 ∙ NCBI:2646 ∙ OMIM:600842 ∙ HGNC:4196 ∙ Uniprot:Q14397 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• not provided (118 variants)
• Inborn genetic diseases (31 variants)
• Fasting plasma glucose level quantitative trait locus 5 (9 variants)
• GCKR-related condition (1 variants)
• not specified (1 variants)
• Hypertriglyceridemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCKR 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			1	8	4	13
missense			69	7	2	78
nonsense			6			6
start loss						0
frameshift			1	1		2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			3			3
splice region			1	5		6
non coding				15	13	28
Total	0	0	81	31	19

Variants in GCKR

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

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

Position	Type	Phenotype	Significance	ClinVar
2-27496896-C-T			Likely benign (Nov 12, 2019)
2-27496913-C-T			Uncertain significance (Sep 14, 2023)
2-27496918-A-G			Uncertain significance (Jul 10, 2020)
2-27496920-C-T			Uncertain significance (Apr 04, 2023)
2-27496919-A-ACGGTTT		Fasting plasma glucose level quantitative trait locus 5	Uncertain significance (Nov 14, 2023)
2-27496921-G-A		not specified	Uncertain significance (Mar 11, 2022)
2-27496946-G-A			Likely benign (Jul 21, 2023)
2-27496954-G-A			Uncertain significance (Sep 21, 2023)
2-27496955-C-T			Uncertain significance (Mar 29, 2022)
2-27496962-G-A			Uncertain significance (Jul 01, 2022)
2-27497254-A-G		not specified	Uncertain significance (Aug 12, 2021)
2-27497256-G-A			Uncertain significance (Aug 24, 2021)
2-27497279-G-T			Uncertain significance (Oct 25, 2022)
2-27497281-A-G		not specified	Uncertain significance (Sep 27, 2022)
2-27497307-G-A			Uncertain significance (Nov 14, 2021)
2-27497310-A-G			Uncertain significance (Jan 23, 2024)
2-27497334-C-T			Conflicting classifications of pathogenicity (Dec 08, 2021)
2-27497335-G-A			Benign (Sep 26, 2023)
2-27497355-G-A		not specified	Uncertain significance (Sep 23, 2023)
2-27497372-G-A			Benign (Jan 31, 2024)
2-27497406-AAG-A			Benign (Jan 31, 2024)
2-27497415-G-T			Likely benign (Aug 14, 2021)
2-27497495-C-G			Likely benign (Jun 25, 2019)
2-27497518-C-T			Benign (Nov 17, 2018)
2-27497554-C-T			Likely benign (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GCKR	protein_coding	protein_coding	ENST00000264717	19	26846

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.54e-19	0.0295	125166	0	582	125748	0.00232

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.14	399	340	1.17	0.0000200	4077
Missense in Polyphen		82	82.992	0.98805		1067
Synonymous	-0.980	146	132	1.11	0.00000777	1256
Loss of Function	0.832	31	36.4	0.851	0.00000213	385

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00453	0.00453
Ashkenazi Jewish	0.00873	0.00877
East Asian	0.00185	0.00185
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00236	0.00235
Middle Eastern	0.00185	0.00185
South Asian	0.00108	0.00108
Other	0.00375	0.00375

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibits glucokinase (GCK) by forming an inactive complex with this enzyme. The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6- phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity. {ECO:0000269|PubMed:23621087, ECO:0000269|PubMed:23733961}.
• Pathway: Wnt Signaling Pathway;Metabolism of carbohydrates;Metabolism;Regulation of Glucokinase by Glucokinase Regulatory Protein;Glycolysis;Glucose metabolism;Wnt (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.325
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.2

Haploinsufficiency Scores

• pHI: 0.297
• hipred: N
• hipred_score: 0.378
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.475

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gckr
• Phenotype: homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: gckr
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: obsolete protein import into nucleus, translocation;carbohydrate metabolic process;regulation of glycolytic process;response to fructose;negative regulation of glucokinase activity;glucose homeostasis;urate metabolic process;triglyceride homeostasis;carbohydrate derivative metabolic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol
• Molecular function: enzyme inhibitor activity;protein binding;enzyme binding;carbohydrate binding;fructose-6-phosphate binding