GCKR

glucokinase regulator

Basic information

Region (hg38): 2:27496839-27523684

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 (177 variants)
not_specified (66 variants)
FASTING_PLASMA_GLUCOSE_LEVEL_QUANTITATIVE_TRAIT_LOCUS_5 (11 variants)
GCKR-related_disorder (6 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. These statistics are base on transcript: NM_000001486.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	25 clinvar	5 clinvar	34
missense		1 clinvar	126 clinvar	11 clinvar	1 clinvar	139
nonsense		1 clinvar	6 clinvar	1 clinvar		8
start loss						0
frameshift			6 clinvar	2 clinvar		8
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	2	151	39	6

Highest pathogenic variant AF is 0.0000340768

Loading clinvar variants...

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