CDKAL1
- Known as:
- CDKAL1
- Catalog number:
- Y214041
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- CDKAL1
Related genes to: CDKAL1
- Gene:
- CDKAL1 NIH gene
- Name:
- CDK5 regulatory subunit associated protein 1 like 1
- Previous symbol:
- -
- Synonyms:
- FLJ20342
- Chromosome:
- 6p22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-12
- Date modifiied:
- 2016-10-05
Related products to: CDKAL1
Related articles to: CDKAL1
- Cdk5 regulatory subunit-associated protein 1-like 1 (Cdkal1) encodes a tRNA-modifying enzyme responsible for thiomethylation generating 2-methylthio-N-threonylcarbamoyladenosine (mstA) in the anticodon loop of tRNA. Genome-wide association studies have identified CDKAL1 variants as risk factors for type 2 diabetes mellitus (DM) and chronic kidney disease (CKD), but whether CKD arises independently of diabetes has remained elusive. Here, we demonstrate that CDKAL1 is required for kidney function and that its dysfunction directly promotes CKD progression independently of diabetes. Systemic and podocyte-specific Cdkal1 knockout in mice leads to CKD phenotypes in later adulthood or after increasing the burden on kidney. Cdkal1-knockout podocytes show reduced lysine-codon translation and decreased levels of lysine-rich proteins, including such that are important for podocyte functions, accompanied by impaired cell migration. These adverse effects on podocytes could be partially reversed by overexpressing CD2AP, a lysine-rich protein. These findings extend the concept of 'tRNA modopathy' to kidney disease and provide mechanistic insights into how defective tRNA modification contributes to kidney disease progression. - Source: PubMed
Publication date: 2026/03/28
Nagata HirokoNagayoshi YuChujo TakeshiKaneko HitomiNishiguchi KayoKakizoe YutakaIjima HirokoSakakida KorinMasuda TakeshiOhtsuki SumioWei Fan-YanTakahashi YukieFukuda TakaichiJinnouchi HideakiAdachi YukiYamamura RyosukeMatsushita KokiAdachi MasatakaYokoi HidekiNakamura KimitoshiNakazato HitoshiTomizawa Kazuhito - Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication with significant short- and long-term consequences for mothers and offspring. While environmental factors, such as obesity and diet, contribute to the risk, genetic predisposition also plays a role in the pathogenesis of GDM. Genome-wide association studies have identified multiple susceptibility loci, including , , and , which represent mechanistically distinct pathways affecting β-cell function, insulin secretion, and peripheral insulin signaling. This review provides a unified mechanistic framework explaining why these three genes, despite individually modest effect sizes, offer complementary insights into GDM pathophysiology that extend beyond other established loci such as . We critically evaluate the current evidence for genetic risk scores in GDM prediction, acknowledging that their incremental predictive value beyond traditional clinical factors remains modest AUC improvement typically <0.05). The integration of genetic variants with epigenetic modifications is discussed, with careful attention to distinguishing causal mechanisms from correlative findings. We emphasize significant limitations in current research, including population stratification, winner's curse effects, and the predominance of East Asian cohorts. While genetic insights may eventually inform risk stratification, substantial barriers remain before clinical implementation, including insufficient predictive accuracy, lack of cost-effectiveness data, and limited generalizability across diverse populations. Future directions include integrating multi-omics data, developing ethnically validated polygenic risk scores, and conducting pragmatic randomized controlled trials to establish the clinical utility of precision prevention strategies. - Source: PubMed
Publication date: 2026/02/27
Turan Guluzar ArzuAran NehirDelibasi Bulent Tolga - : Gestational diabetes mellitus (GDM) poses a growing public health challenge worldwide due to its increasing prevalence, associated pregnancy complications, and long-term metabolic risks for both mothers and offspring. Genetic factors are known to contribute to GDM susceptibility, yet little is known about their relevance in ethnic Kazakh population. The primary objective of this study was to evaluate associations between selected candidate SNPs involved in β-cell function and the risk of GDM in a Kazakh cohort. Secondary objectives included the assessment of potential gene-gene interactions. : We conducted a case-control study among 365 pregnant Kazakh women. Of these, 217 were diagnosed with GDM, and 148 had normal glucose tolerance. Clinical and genealogical data were collected. Eight candidate SNPs that were previously associated with GDM or glucose metabolism were genotyped. Logistic regression was used to assess associations between SNPs and GDM risk. Gene-gene interactions were evaluated using multifactor dimensionality reduction (MDR). : In univariate analysis, rs10830963 demonstrated a statistically significant association under the additive model (OR 0.61, 95% CI 0.42-0.89), indicating a potential protective effect of the C allele. However, this association was not statistically significant after multivariable adjustment (adjusted OR 0.58, 95% CI 0.32-1.03) and correction for multiple testing. In the adjusted analysis, rs7903146 showed a significant association under the dominant model (adjusted OR 2.29, 95% CI 1.01-5.46); however, this finding did not remain significant following FDR correction. MDR analysis showed that the best two-locus model included rs4402960 and rs7754840 (CVC = 6/10; testing accuracy = 0.558; permutation < 0.001). The most stable interaction was observed for the three-locus model comprising rs4402960, rs10830963, and rs1801282 (CVC = 9/10; testing accuracy = 0.576; permutation < 0.001). : The findings suggest that common variants in , , , , and do not exert strong individual effects on GDM susceptibility in this cohort of ethnic Kazakh women. Instead, the results are more consistent with a modest polygenic architecture characterized by small effect sizes and possible weak gene-gene interactions. MDR analysis identified statistically significant interaction models; however, their limited predictive accuracy indicates that these findings should be interpreted as exploratory. - Source: PubMed
Publication date: 2026/02/25
Danyarova LauraSvyatova GulnaraBerezina GalinaTuleutayev RustemSultanova BalnurTaigulova AsselSartayeva AigulZhekeyeva MoldirKaribayeva Indira - We aimed to investigate whether maternal and fetal genetic predispositions to insulin deficiency and resistance affect offspring fetal growth through distinct pathways in multi-ethnic populations. - Source: PubMed
Publication date: 2026/02/03
Yu GechangTam Claudia H TShi MaiHughes Alice EHuang ChuiguoDeng YuzhiWeedon Michael NLim Cadmon K PWang Chi ChiuChan Juliana C NTam Wing HungLowe WilliamFreathy Rachel MOram Richard AMa Ronald C W - Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with significant short- and long-term risks for both mother and offspring. Increasing evidence indicates that genetic susceptibility plays a central role in GDM pathogenesis, particularly through variants affecting insulin secretion and pancreatic β-cell function. This narrative review integrates molecular, clinical, and epidemiological perspectives, highlighting population-specific effects and gene-environment interactions. Improved understanding of the genetic risk architecture may support earlier risk stratification and enable the future development of personalized strategies for GDM prevention and management, with particular emphasis on genetic polymorphisms in , , and genes consistently implicated in glucose homeostasis and β-cell integrity. These genes contribute to distinct but complementary molecular pathways underlying GDM, including impaired insulin biosynthesis, defective zinc transport within insulin granules, and altered paracrine regulation within pancreatic islets. While associations between these variants and GDM have been repeatedly demonstrated, their clinical relevance and mechanistic impact remain incompletely understood. Available evidence suggests that represents the strongest genetic determinant, followed by , while appears to play a modulatory role. This review summarizes current findings on the molecular functions and clinical significance of these polymorphisms, highlighting population-specific effects and gene-environment interactions. Improved understanding of genetic risk architecture may support earlier risk stratification and enable future development of personalized strategies for GDM prevention and management. - Source: PubMed
Publication date: 2026/01/22
Hryniewicka JustynaBuczyńska-Backiel AngelikaZbucka-Krętowska MonikaKrętowski Adam JacekSzelachowska Małgorzata