{{Rsnum
|rsid=1260326
|Gene=GCKR
|Chromosome=2
|position=27508073
|Orientation=plus
|ReferenceAllele=C
|MissenseAllele=T
|GMAF=0.3848
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|effect1=
|effect2=
|effect3=
|Gene_s=GCKR
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 33.0 | 50.0 | 17.0
| HCB | 17.6 | 50.0 | 32.4
| JPT | 21.4 | 44.6 | 33.9
| YRI | 81.5 | 17.1 | 1.4
| ASW | 76.8 | 21.4 | 1.8
| CHB | 17.6 | 50.0 | 32.4
| CHD | 22.0 | 45.9 | 32.1
| GIH | 62.4 | 33.7 | 4.0
| LWK | 79.8 | 18.3 | 1.8
| MEX | 45.6 | 40.4 | 14.0
| MKK | 73.4 | 26.0 | 0.6
| TSI | 20.6 | 55.9 | 23.5
| HapMapRevision=28
}}

The T allele of [[rs1260326]] has been associated with [[type 2 diabetes]] and [[hypertriglyceridemia]].

{{PMID|18678614|OA=1
}} A fine mapping approach indicates that this SNP, [[rs1260326]], shows the strongest association signal with metabolic phenotypes in the region that also harbors the tightly linked (r(2)=0.93) SNP [[rs780094]], which has been previously associated with triglyceride and glucose concentrations. This SNP, [[rs1260326]], encodes a common missense glucokinase regulatory protein gene [[GCKR]] variant.

{{PMID Auto GWAS
|PMID=19060906
|Trait=Triglycerides
|Title=Common variants at 30 loci contribute to polygenic dyslipidemia
|RiskAllele=T
|Pval=2E-31
|OR=0.12
|ORtxt=[0.08-0.16] SD increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=19060910
|Trait=Other metabolic traits
|Title=Genome-wide association analysis of metabolic traits in a birth cohort from a founder population
|RiskAllele=A
|Pval=4E-10
|OR=0.09
|ORtxt=[0.06-0.12] mmol/l increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=18454146
|Trait=Waist circumference and related phenotypes
|Title=Common genetic variation near MC4R is associated with waist circumference and insulin resistance
|RiskAllele=
|Pval=4.0000000000000001E-8
|OR=NR
|ORtxt=NR
}}

{{PMID Auto
|PMID=19526250
|Title=Glucokinase regulatory protein gene polymorphism affects postprandial lipemic response in a dietary intervention study
|OA=1
}}

{{PMID Auto
|PMID=19651812
|Title=Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type-2 diabetes amongst Indian Asians and European whites
|OA=1
}}

{{PharmGKB
|RSID=rs1260326
|Name_s=
|Gene_s=GCKR
|Feature=
|Evidence=PubMed ID:19802338
|Annotation=Phenotype: In a GWAS, this SNP was significantly associated with plasma concentrations of triglycerides. Study size:6382. Study population/ethnicity: Caucasian women. Significance metric(s): P = 1.3 x 10(-16). Type of association: CO; GN
|Drugs=
|Drug Classes=
|Diseases=Cardiovascular Diseases
|Curation Level=Curated
|PharmGKB Accession ID=PA165111808
}}

{{PMID Auto GWAS
|PMID=20081857
|Trait=Two-hour glucose challenge
|Title=Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
|RiskAllele=T
|Pval=3E-10
|OR=0.07
|ORtxt=[0.05-0.09] mmol/L increase
|OA=1
}}

{{PMID Auto GWAS
|PMID=20139978
|Trait=Hematological and biochemical traits
|Title=Genome-wide association study of hematological and biochemical traits in a Japanese population
|RiskAllele=C
|Pval=4E-9
|OR=0.36
|ORtxt=[NR] % variance
}}
{{PMID Auto GWAS
|PMID=20383146
|Trait=Chronic kidney disease
|Title=New loci associated with kidney function and chronic kidney disease
|RiskAllele=T
|Pval=3E-14
|OR=0.01
|ORtxt=[0.007-0.011] ml/min/1.73 m2 increase
|OA=1
}}
{{PMID Auto
|PMID=20802025
|Title=Genome-wide association study identifies novel loci for plasma levels of protein C: the ARIC study
|OA=1
}}
{{PMID Auto GWAS
|PMID=20657596
|Trait=Hypertriglyceridemia
|Title=Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia
|RiskAllele=T
|Pval=7E-9
|OR=1.75
|ORtxt=[1.45-2.12]
|OA=1
}}
{{PMID Auto
|PMID=20352598
|Title=Glucokinase-activating GCKR polymorphisms increase plasma levels of triglycerides and free fatty acids, but do not elevate cardiovascular risk in the Ludwigshafen Risk and Cardiovascular Health Study
}}

{{omim
|id=600842
|desc=GLUCOKINASE REGULATORY PROTEIN; GCKR
|rsnum=1260326
}}

{{PharmGKB
|RSID=rs1260326
|Name_s=
|Gene_s=GCKR
|Feature=
|Evidence=PubMed ID:19060910; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. (Initial Sample Size: 4,763 individuals; Replication Sample Size: NR); (Region: 2p23.3; Reported Gene(s): GCKR; Risk Allele: rs1260326-A); (p-value= 0.0000000004).This variant is associated with Other metabolic traits.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740290
}}

{{PharmGKB
|RSID=rs1260326
|Name_s=
|Gene_s=GCKR
|Feature=
|Evidence=PubMed ID:19060906; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Common variants at 30 loci contribute to polygenic dyslipidemia. (Initial Sample Size: 19,840 individuals; Replication Sample Size: Up to 20,623 individuals); (Region: 2p23.3; Reported Gene(s): GCKR; Risk Allele: rs1260326-T); (p-value= 2E-31).This variant is associated with Triglycerides.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740264
}}

{{PharmGKB
|RSID=rs1260326
|Name_s=
|Gene_s=GCKR
|Feature=
|Evidence=PubMed ID:20081857
|Annotation=Risk or phenotype-associated allele: T . Phenotype: In a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620), this SNP was found to be associated with 2-h glucose level (a clinical measure of glucose tolerance). Effect (s.e.m.) = 0.07(0.01) mmol/l per T allele. Study size/population/ethnicity: 15,234 plus 6,958-30,620 nondiabetic individuals of European descent. Significance metric(s): p = 7.05 x 10(-11). Type of association: CO;GN.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA165281983
}}

{{omim
|id=600842
|rsnum=1260326
|variant=0001
}}

{{PMID Auto GWAS
|PMID=21300955
|Trait=None
|Title=Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
|RiskAllele=T
|Pval=5E-40
|OR=0.0720
|ORtxt=[0.06-0.08] unit increase
|OA=1
}}

{{PMID Auto
|PMID=21525158
|Title=Triglyceride Response to an Intensive Lifestyle Intervention Is Enhanced in Carriers of the GCKR Pro446Leu Polymorphism
|OA=1
}}

{{PMID Auto
|PMID=22105854
|Title=A variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents
|OA=1
}}

{{PMID Auto GWAS
|PMID=22139419
|Trait=None
|Title=New gene functions in megakaryopoiesis and platelet formation.
|RiskAllele=T
|Pval=9E-10
|OR=2.3340
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=22001757
|Trait=None
|Title=Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
|RiskAllele=T
|Pval=4E-13
|OR=3.2000
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=21943158
|Trait=None
|Title=Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.
|RiskAllele=T
|Pval=2E-8
|OR=0.0820
|ORtxt=[0.053-0.111] mmol/l increase
|OA=1
}}

{{PMID Auto GWAS
|PMID=20686565
|Trait=None
|Title=Biological, clinical and population relevance of 95 loci for blood lipids.
|RiskAllele=T
|Pval=0
|OR=8.7600
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=22716779
|Title=Relevant associations of the glucokinase regulatory protein/glucokinase gene variation with TAG concentrations in a high-cardiovascular risk population: modulation by the Mediterranean diet
}}

{{PMID Auto GWAS
|PMID=22558069
|Trait=None
|Title=Association of common variants in TNFRSF13B, TNFSF13, and ANXA3 with serum levels of non-albumin protein and immunoglobulin isotypes in Japanese.
|RiskAllele=C
|Pval=3E-9
|OR=0.0800
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=22286219
|Trait=None
|Title=Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
|RiskAllele=
|Pval=3E-18
|OR=0.1500
|ORtxt=None
|OA=1
}}

{{PMID|18439548|OA=1
}} Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.

{{PMID|18439552|OA=1
}} Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein.

{{PMID|18556336|OA=1
}} The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population.

{{PMID|18853134}} The search for putative unifying genetic factors for components of the metabolic syndrome.

{{PMID|19073768|OA=1
}} Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents.

{{PMID|19148283|OA=1
}} Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson Heart Study.

{{PMID|19299407|OA=1
}} Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample.

{{PMID|19474294|OA=1
}} Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.

{{PMID|19533084|OA=1
}} Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk.

{{PMID|19656773|OA=1
}} A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia.

{{PMID|19847674}} Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes in ischemic stroke.

{{PMID|19913121|OA=1
}} Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

{{PMID|20160193|OA=1
}} Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples.

{{PMID|20339536|OA=1
}} Genome-wide association of lipid-lowering response to statins in combined study populations.

{{PMID|20570915}} Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

{{PMID|20628598|OA=1
}} Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.

{{PMID|20661421|OA=1
}} Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study.

{{PMID|21071687}} TRIB1 and GCKR polymorphisms, lipid levels, and risk of ischemic heart disease in the general population.

{{PMID|21423719|OA=1
}} Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

{{PMID|21647738|OA=1
}} Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment.

{{GET Evidence
|gene=GCKR
|aa_change=Leu446Pro
|aa_change_short=L446P
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1260326
|overall_frequency_n=7302
|overall_frequency_d=10758
|overall_frequency=0.678751
|n_genomes=52
|n_genomes_annotated=0
|n_haplomes=78
|n_articles=2
|n_articles_annotated=2
|qualityscore_in_silico=3
|qualitycomment_in_silico=Y
|in_gwas=Y
|in_pharmgkb=Y
|nblosum100=7
|autoscore=2
|webscore=N
}}

{{PMID Auto GWAS
  |PMID=23022100
  |Trait=Serum albumin level
  |Title=Discovery and fine mapping of serum protein loci through transethnic meta-analysis.
  |RiskAllele=T
  |Pval=4E-19
  |OR=.01
  |ORtxt=[0.011-0.017] unit increase
  |OA=1
}}

{{PMID Auto GWAS
  |PMID=23118302
  |Trait=Lipoprotein-associated phospholipase A2 activity and mass
  |Title=Genome-wide association study evaluating lipoprotein-associated phospholipase A2 mass and activity at baseline and after rosuvastatin therapy.
  |RiskAllele=T
  |Pval=5E-6
  |OR=.01
  |ORtxt=[-0.00215-0.01275] ng/ml decrease
  }}

{{PMID Auto GWAS
  |PMID=23263486
  |Trait=Urate levels
  |Title=Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
  |RiskAllele=T
  |Pval=1E-44
  |OR=.07
  |ORtxt=[0.063-0.084] mg/dl increase
  |OA=1
}}

{{PMID Auto GWAS
  |PMID=22916037
  |Trait=Metabolite levels
  |Title=Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
  |RiskAllele=
  |Pval=1E-12
  |OR=NR
  |ORtxt=NR
  |OA=1
}}

{{PMID Auto GWAS
  |PMID=23505323
  |Trait=Hypertriglyceridemia
  |Title=Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.
  |RiskAllele=
  |Pval=2E-13
  |OR=1.41
  |ORtxt=[1.31-1.51]
  |OA=1
}}

{{ClinVar
|ALT=C
|CAF=0.3848; 0.6152
|CHROM=2
|CLNACC=RCV000009294.1
|CLNALLE=1
|CLNDBN=Fasting plasma glucose level quantitative trait locus 5
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=C3150714:613463
|CLNHGVS=NC_000002.11:g.27730940T>C
|CLNSIG=255
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=600842.0001
|COMMON=1
|Disease=Fasting plasma glucose level quantitative trait locus 5
|FwdALT=C
|FwdREF=T
|GENEINFO=GCKR:2646
|GENE_ID=2646
|GENE_NAME=GCKR
|REF=T
|RSPOS=27730940
|Reversed=0
|SAO=0
|SSR=0
|Tags=PM;PMC;SLO;VLD;G5A;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|VC=SNV
|VP=0x05016800000017051f130101
|WGT=0
|dbSNPBuildID=87
|rsid=1260326
}}

{{PMID Auto GWAS
  |PMID=23903356
  |Trait=Glycemic traits (pregnancy)
  |Title=Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
  |RiskAllele=T
  |Pval=6E-13
  |OR=.00
  |ORtxt=[NR] unit decrease
  }}

{{PMID Auto
|PMID=22517333
|Title=Associations of apolipoprotein A5 (APOA5), glucokinase (GCK) and glucokinase regulatory protein (GCKR) polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese - a cross-sectional data from the J-MICC Study.
}}

{{PMID Auto
|PMID=23092954
|Title=SHAVE: shrinkage estimator measured for multiple visits increases power in GWAS of quantitative traits.
|OA=1
}}

{{PMID Auto
|PMID=23275357
|Title=The association between hepatic fat content and liver injury in obese children and adolescents: effects of ethnicity, insulin resistance, and common gene variants.
|OA=1
}}

{{PMID Auto
|PMID=23586973
|Title=Investigation of known estimated glomerular filtration rate loci in patients with Type 2 diabetes.
}}

{{PMID Auto
|PMID=23800943
|Title=Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene.
}}

{{PMID Auto
|PMID=23832694
|Title=Common genetic variants associated with lipid profiles in a Chinese pediatric population.
}}

{{PMID Auto
|PMID=24799990
|Title=Pediatric non-alcoholic fatty liver disease: New insights and future directions
|OA=1
}}

{{PMID Auto GWAS
  |PMID=24386095
  |Trait=Lipid traits
  |Title=A genome wide association study identifies common variants associated with lipid levels in the Chinese population.
  |RiskAllele=T
  |Pval=3E-7
  |OR=.07
  |ORtxt=mmol/L increase
  }}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}