CDKAL1

General Information

Full gene name:CDK5 regulatory subunit associated protein 1-like 1 Entrez Gene ID:54901 Location:6p22.3 Synonyms: Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP	Distance (bp)	Direction
rs7754840	0	within

NCBI Summary

The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

OMIM

OMIM ID:`OMIM ID 611259 `_

Allelic Variants (Selected Examples)

.0001 DIABETES MELLITUS, NONINSULIN-DEPENDENT, SUSCEPTIBILITY TO

In genomewide association studies of type 2 DIABETES (125853), the DIABETES Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Reserch (2007), Zeggini et al. (2007), and Scott et al. (2007) identified association of the C allele of a SNP in intron 5 of the CDKAL1 gene, rs10946398, or of its proxy, rs7754840, with type 2 DIABETES. Across these studies, all groups cited evidence for association at this marker of P approximately equal to 4.1 x 10(-11).

.0002 DIABETES MELLITUS, NONINSULIN-DEPENDENT, SUSCEPTIBILITY TO

Steinthorsdottir et al. (2007) identified a variant in intron 5 of the CDKAL1 gene, rs7756992, that was associated with type 2 DIABETES (125853) in individuals of European ancestry (allele-specific OR, 1.20; P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR, 1.25; P = 0.00018). The ORs for homozygotes were 1.50 and 1.55 in the European and Hong Kong groups, respectively. The INSULIN response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers (P = 2.5 x 10(-8)), suggesting that this variant confers risk of type 2 DIABETES through reduced INSULIN secretion.

NCBI Phenotypes

• Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
• A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.
• Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia.
• Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data.
• A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
• Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases.
• Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease.
• OMIM
• Gene Reviews
• Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.
• Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
• Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.
• Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
• GTR
• Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
• Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
• Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations.
• Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study.
• A genome-wide association study of gestational diabetes mellitus in Korean women.
• Meta-analysis identifies common variants associated with body mass index in east Asians.
• Diabetes mellitus type 2
• NHGRI GWA Catalog
• SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations.
• Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
• A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.

Gene Ontology

• molecular_function
• transferase activity
• RNA modification
• cellular_component
• metal ion binding
• integral to membrane
• biological_process
• 4 iron, 4 sulfur cluster binding
• tRNA processing

KEGG Pathways

No pathways found linked to this gene.

GeneRIFs

• Single nucleotide polymorphism (SNP) analysis revealed that the sequence variant (rs5015480) near HHEX and two SNPs (rs7756992 and rs9465871) in CDKAL1 were associated with the susceptibility of type 2 diabetes mellitus in females, but not in males. [PMID 21368910]
• ADAM33, CDKAL1, and PTPN22 may be true psoriasis-risk genes [PMID 18923449]
• Type 2 diabetes susceptibility alleles at CDKAL1 are associated with low body mass index at 8 years in children who were born large for gestational age. [PMID 20460429]
• no relationship of CDKAL1 and KCNQ1 polymorphisms to the earlier onset of type 2 diabetes was observed [PMID 21416855]
• CDKAL1 alleles may confer susceptibility to clinically distinct disorders through differential effects on disease-specific cell types. [PMID 19587699]
• Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 19734900]
• Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) [PMID 20379614]
• Interaction between the CDKAL1 polymorphism and dietary energy intake influences the dysglycemic phenotype leading to MetS, possibly through impaired insulin secretion. The CDKAL1 polymorphism may be a marker for MetS in the Japanese population. [PMID 20847106]
• Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator) [PMID 20847106]
• Meta-analysis and HuGE review of gene-disease association. (HuGE Navigator) [PMID 19602701]
• Observational study and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 20014019]
• Variants of CDKAL1 and IGF2BP2 attenuate the first phase of glucose-stimulated insulin secretion but show no effect on the second phase of insulin secretion in hyperglycmia and type 2 diabetes. [PMID 18618095]
• Studies identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities. [PMID 20161779]
• Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 20879858]
• Positive association between single nucleotide polymorphisms in this gene with type 2 diabetes in Han Chinese. [PMID 18766326]
• The underlying mechanisms linking CDKAL1, glutamate decarboxylase, and insulin secretion are unclear. A recent case-control study found no association of variation in CDKAL1 with type 1 diabete.s [PMID 18753662]
• A significant association between Type 2 Diabetes Mellitus, an increased Fasting Plasma Glucose and rs7754840 at CDKAL1 in lean Han Chinese. [PMID 21643948]
• CDKAL1 might influence the level of glycosylated hemoglobin [PMID 22290723]
• Type 2 diabetes susceptibility of CDKAL1 was confirmed in Japanese. [PMID 19033397]
• One SNP, rs7754840 in the CDKAL1 gene, presented a significantly stronger effect in the Ashkenazi Jewish population as compared to the general Caucasian population for type 2 diabetes susceptibility. [PMID 18516622]
• Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 20628086]
• Six SNP(rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK)risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. [PMID 22096510]
• Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations. [PMID 22344221]
• Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) [PMID 20886065]
• Diabetes-associated variants in TCF7L2 and CDKAL1 impair insulin secretion and conversion of proinsulin to insulin. [PMID 18264689]
• there are significant associations between CDKAL1 polymorphisms and type 2 diabetes [meta-analysis] [PMID 20568056]
• Meta-analysis of gene-disease association. (HuGE Navigator) [PMID 20568056]
• Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator) [PMID 20889853]
• CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion. [PMID 18285412]
• Genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 18587394]
• The associations between SNPs of TCF7L2, CDKAL1, SLC30A8 and HHEX and the development of DR and DN. [PMID 22487833]
• Study show that polymorphisms in CDKAL1 were associated with type 2 diabetes risk in the studied population. [PMID 18694974]
• Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and genetic testing. (HuGE Navigator) [PMID 20075150]
• Single nucleotide polymorphism in CDKAL1 is associated with type 2 diabetes. [PMID 18991055]
• CDKAL1 and HHEX/IDE diabetes-associated alleles are associated with decreased pancreatic beta-cell function, including decreased beta-cell glucose sensitivity that relates insulin secretion to plasma glucose concentration. [PMID 17804762]
• CDKAL1 is involved in the pathogenesis of T2 diabetes through impaired beta-cell function. [PMID 21611789]
• Association between lower birth weight and type 2 diabetes risk-conferring alleles at the CDKAL1 locus. [PMID 19592620]
• The presence of a C-allele at the CDKAL1 single nucleotide polymorphism rs6908425 and the absence of NOD2 variants were independently associated with development of perianal fistula [PMID 19422935]
• Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 17463249]
• Gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population. [PMID 18597214]
• Observational study of gene-disease association. (HuGE Navigator) [PMID 21072187]
• there is an association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes in the Chinese population [PMID 19862325]
• CDKAL1 rs7754840 and rs7756992, but not CDKN2A/2B rs10811661, are associated with T2DM in Lebanese. [PMID 22119613]
• Data show that SNPs in CDKAL1 did not confer a significant risk for type 2 diabetes in Pima Indians. [PMID 19008344]
• Affinity Capture-MS [PMID 21906983]
• Data confirmed the associations of single nucleotide polymorphisms in CDKAL1 with risk for type 2 diabetes in Asians. [PMID 18469204]
• The results indicate that in Chinese Hans, common variants in CDKAL1 loci independently or additively contribute to type 2 diabetes risk, likely mediated through beta-cell dysfunction. [PMID 18633108]
• Single nucleotide polymorphisms in CDKAL1 have no association with polycystic ovary syndrome or related clinical features in Chinese women. [PMID 19718565]
• Variants in cdkal1 gene have been reproducibly associated with decreased first-phase insulin secretion and development of type 2 diabetes. [PMID 21908934]
• Data report a novel association between the fetal ADCY5 type 2 diabetes risk allele and decreased birthweight, and confirm in meta-analyses associations between decreased birthweight and the type 2 diabetes risk alleles of HHEX-IDE and CDKAL1. [PMID 20490451]
• Observational study and meta-analysis of gene-disease association. (HuGE Navigator) [PMID 20490451]
• Single Nucleotide polymorphism in CDK5 regulatory subunit associated protein 1-like 1 is associated with type 2 diabetes [PMID 17460697]
• The association of 6 loci with type 2 diabetes risk in Japanese patients is reported. [PMID 18162508]

PubMed Articles

Recent articles:

• Perry JR et al. “Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases.” PLoS Genet. 2012 May;8(5):e1002741. PMID 22693455
• Estrada K et al. “Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.” Nat Genet. 2012 Apr 15;44(5):491-501. PMID 22504420
• Fu LL et al. “[Association analysis of genetic polymorphisms of TCF7L2, CDKAL1, SLC30A8, HHEX genes and microvascular complications of type 2 diabetes mellitus].” Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Apr;29(2):194-9. PMID 22487833
• Ryu J et al. “Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study.” Hum Mutat. 2012 Apr;33(4):655-9. PMID 22290723
• Okada Y et al. “Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations.” Nat Genet. 2012 Feb 19;44(3):302-6. PMID 22344221
• Wen W et al. “Meta-analysis identifies common variants associated with body mass index in east Asians.” Nat Genet. 2012 Feb 19;44(3):307-11. PMID 22344219
• Kwak SH et al. “A genome-wide association study of gestational diabetes mellitus in Korean women.” Diabetes. 2012 Feb;61(2):531-41. PMID 22233651
• Nemr R et al. “Replication study of common variants in CDKAL1 and CDKN2A/2B genes associated with type 2 diabetes in Lebanese Arab population.” Diabetes Res Clin Pract. 2012 Feb;95(2):e37-40. PMID 22119613
• Wang Y et al. “Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.” PLoS One. 2011;6(11):e26953. PMID 22096510
• Wei FY et al. “Functional loss of Cdkal1, a novel tRNA modification enzyme, causes the development of type 2 diabetes.” Endocr J. 2011;58(10):819-25. PMID 21908934

Top Pubmed articles linked to gene CDKAL1 matching any search term:

• Iwata M et al. “Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals.” Diabetes Care. 2012 Aug;35(8):1763-70. PMID 22688542
• Ekelund M et al. “Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus.” Diabetes Res Clin Pract. 2012 May 14;. PMID 22591707
• Lu F et al. “Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case-control study in Han Chinese.” J Hum Genet. 2012 May;57(5):320-5. PMID 22437209
• Sainz J et al. “Effect of type 2 diabetes predisposing genetic variants on colorectal cancer risk.” J Clin Endocrinol Metab. 2012 May;97(5):E845-51. PMID 22419714
• Winkler C et al. “Lack of association of type 2 diabetes susceptibility genotypes and body weight on the development of islet autoimmunity and type 1 diabetes.” PLoS One. 2012;7(4):e35410. PMID 22558147
• Campbell DD et al. “Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population.” PLoS One. 2012;7(4):e33570. PMID 22529894
• Fu LL et al. “[Association analysis of genetic polymorphisms of TCF7L2, CDKAL1, SLC30A8, HHEX genes and microvascular complications of type 2 diabetes mellitus].” Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Apr;29(2):194-9. PMID 22487833
• Cauchi S et al. “European genetic variants associated with type 2 diabetes in North African Arabs.” Diabetes Metab. 2012 Mar 29;. PMID 22463974
• Kim JJ et al. “Polycystic ovary syndrome is not associated with polymorphisms of the TCF7L2, CDKAL1, HHEX, KCNJ11, FTO and SLC30A8 genes.” Clin Endocrinol (Oxf). 2012 Mar 24;. PMID 22443257
• Sanda S et al. “A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.” Acta Diabetol. 2012 Mar 22;. PMID 22438186
• Wang Y et al. “Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.” PLoS One. 2011;6(11):e26953. PMID 22096510
• Ryoo H et al. “Heterogeneity of genetic associations of CDKAL1 and HHEX with susceptibility of type 2 diabetes mellitus by gender.” Eur J Hum Genet. 2011 Jun;19(6):672-5. PMID 21368910
• Sim X et al. “Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.” PLoS Genet. 2011 Apr;7(4):e1001363. PMID 21490949
• Dobríková M et al. “[Relationship of the CDKAL1 and KCNQ1 gene polymorphisms to the age at diagnosis of type 2 diabetes in the Slovakian population].” Vnitr Lek. 2011 Feb;57(2):155-8. PMID 21416855
• Miyaki K et al. “Association of a cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) polymorphism with elevated hemoglobin A₁(c) levels and the prevalence of metabolic syndrome in Japanese men: interaction with dietary energy intake.” Am J Epidemiol. 2010 Nov 1;172(9):985-91. PMID 20847106
• Rotger M et al. “Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.” Clin Infect Dis. 2010 Nov 1;51(9):1090-8. PMID 20879858
• Stuebe AM et al. “Obesity and diabetes genetic variants associated with gestational weight gain.” Am J Obstet Gynecol. 2010 Sep;203(3):283.e1-17. PMID 20816152
• Pechlivanis S et al. “Coronary artery calcification and its relationship to validated genetic variants for diabetes mellitus assessed in the Heinz Nixdorf recall cohort.” Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1867-72. PMID 20616309
• Winkler C et al. “BMI at age 8 years is influenced by the type 2 diabetes susceptibility genes HHEX-IDE and CDKAL1.” Diabetes. 2010 Aug;59(8):2063-7. PMID 20460429
• Haupt A et al. “The risk allele load accelerates the age-dependent decline in beta cell function.” Diabetologia. 2009 Mar;52(3):457-62. PMID 19172244