Ask about this productRelated genes to: CDKL2 antibody
- Gene:
- CDKL2 NIH gene
- Name:
- cyclin dependent kinase like 2
- Previous symbol:
- -
- Synonyms:
- P56, KKIAMRE
- Chromosome:
- 4q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-07
- Date modifiied:
- 2016-10-05
Related products to: CDKL2 antibody
Related articles to: CDKL2 antibody
- Neuropsychiatric symptoms (NPS), commonly concomitant with Alzheimer's disease (AD), substantially impair the quality of life and accelerate disease progression, yet reliable biomarkers for early identification of individuals at high NPS risk remain elusive. In this study, we leveraged the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), incorporating longitudinal data from 509 participants diagnosed with mild cognitive impairment (MCI) or mild AD at baseline and followed up for 1 and 2 years. The dataset included cerebrospinal fluid (CSF) proteomic profiles comprising 6361 proteins, along with comprehensive data on NPS diagnosis, cognitive function, and AD pathology. LASSO regression and recursive feature elimination were applied to identify NPS-related CSF proteins, followed by random forest modeling to predict NPS risk at baseline, 1 year, and 2 years. Incorporating selected CSF proteins significantly improved NPS prediction compared to the reference model, with AUCs increasing from 0.64 to 0.76 at baseline, 0.63 to 0.80 at 1 year, and 0.63 to 0.81 at 2 years. Notably, Cyclin-Dependent Kinase-Like 2 (CDKL2), Nidogen 2 (NID2), and Lin-7 Homolog B (LIN7B) were consistently associated with NPS across all time points. Among them, CDKL2 and NID2 were significantly associated with AD biomarkers and cognitive scores, and their expression changes were independently validated in cerebrospinal fluid from a mouse model, highlighting their potential as stable predictive biomarkers. Our findings highlight CSF proteomic signatures that robustly predict NPS progression in individuals with MCI and mild AD, offering a framework for early risk stratification and precision intervention in NPS. - Source: PubMed
Han XueZhu ShouqiangZhang HengXia TianjiaoGu Xiaoping - This study aimed to identify key genes regulating plasma cell (PC) infiltration in kidney renal clear cell carcinoma (KIRC) and construct a novel prognostic model for predicting KIRC. Clear cell renal cell carcinoma is the most common malignant tumor type of the kidney, with an increasing incidence rate and low survival rates in advanced patients. Plasma cells (PCs), as terminally differentiated B cells, produce highly specific antibodies that effectively target and kill tumors through the antibody-dependent cellular cytotoxicity (ADCC) mechanism. Growing evidence has shown that PC infiltration is closely associated with the progression of various malignant tumors, including ccRCC. Therefore, identifying PC infiltration-related biomarkers is of great significance for the prognosis and treatment of ccRCC patients. Machine learning was used to determine PC-related key genes in KIRC patients. A prognostic model termed PC score was developed using TCGA and ArrayExpress data and validated in external cohorts. The molecular background, immune characteristics, and drug sensitivity of the high PC score group were evaluated. Single-cell sequencing was employed to assess the expression of hub genes in KIRC patients. We identified 9 hub genes associated with PC infiltration, including 3 risk genes (ADAM8, KCNN4, and TCIRG1) and 6 protective genes (RAG1, ATPEV1D, CDKL2, RUNDC3B, SLC30A9, and PPARGC1A), and constructed a PC score based on these key genes. Older age, advanced TNM stage, and higher PC score were independent predictors of shorter overall survival. A nomogram model integrating age, stage, and PC score showed significantly higher predictive value than staging alone (P < 0.01). The high PC score group exhibited a higher abundance of immune cells (e.g., activated B cells, activated CD8 + T cells) in the tumor microenvironment. Drug sensitivity analysis revealed that tyrosine kinase inhibitors (e.g., ceritinib, imatinib) potently inhibited cancer cell lines in the high PC score group, while inhibitors like acalabrutinib were effective in the low PC score group. Patients with higher risk scores showed greater sensitivity to ofloxacin and cortivazol (a cortisol hormone). Expression of hub genes in KIRC patients was validated using a local cohort and single-cell sequencing. We identified key genes regulating PC infiltration in KIRC and proposed a predictive model that effectively identifies high-risk KIRC patients. - Source: PubMed
Publication date: 2025/11/11
Sun XintongYang YuchangLiu MingxuNiu ChengtaoCong ZixiangHe WeiNiu Zhihong - The advent of genetic biobanking has powered gene-environment interaction (GxE) studies in various disease contexts. Therefore, we aimed to discover novel GxE effects that address hot spring residency as a risk to inconspicuous disease association. - Source: PubMed
Publication date: 2025/10/22
Wu Hsin-YuChang Kao-JungChiu WeiWang Ching-YunLin Yi-ChenHsu Yu-TienWen Yuan-ChihChiang Pin-HsuanChen Yu-HsiangDai He-JhenLu Chia-HsinChen Yi-ChengTsai Han-YingChen Yu-ChunHsu Chih-HungChiou Shih-HwaYang Yi-PingHsieh Ai-RuHsu Chih-Chien - The CDKL (cyclin-dependent kinase-like) family consists of five members in humans, CDKL1-5, that encode serine-threonine kinases. The only member that has been associated with a Mendelian disorder is CDKL5, and variants in CDKL5 cause developmental and epileptic encephalopathy type 2 (DEE2). Here, we study four de novo variants in CDKL2 identified in five individuals, including three unrelated probands and monozygotic twins. These individuals present with overlapping symptoms, including global developmental delay, intellectual disability, childhood-onset epilepsy, dyspraxia, and speech deficits. We also identified two individuals with de novo missense variants in CDKL1 in the published Deciphering Developmental Disorders (DDD) and GeneDx cohorts with developmental disorders. Drosophila has a single ortholog of CDKL1-5, CG7236 (Cdkl). Cdkl is expressed in sensory neurons that project to specific regions of the brain that control sensory inputs. Cdkl loss causes semi-lethality, climbing defects, heat-induced seizures, hearing loss, and reduced lifespan. These phenotypes can be rescued by expression of the human reference CDKL1, CDKL2, or CDKL5, showing that the functions of these genes are conserved. In contrast, the CDKL1 and CDKL2 variants do not fully rescue the observed phenotypes, and overexpression of the variant proteins leads to phenotypes that are similar to Cdkl loss. Co-expression of CDKL1 or CDKL2 variants with CDKL1, CDKL2, or CDKL5 references in the mutant background suppresses the rescue ability of the reference genes. Our results suggest that the variants act as dominant negative alleles and are causative of neurological symptoms in these individuals. - Source: PubMed
Publication date: 2025/03/14
Bereshneh Ali HAndrews Jonathan CEberl Daniel FBademci GuneyBorja Nicholas ABivona Stephanie Chung Wendy KYamamoto ShinyaWangler Michael FMcKee ShaneTekin MustafaBellen Hugo JKanca Oguz - Acylaminoindazole-based inhibitors of CDKL2 were identified via analyses of cell-free binding and selectivity data. Compound was selected as a CDKL2 chemical probe based on its potent inhibition of CDKL2 enzymatic activity, engagement of CDKL2 in cells, and excellent kinome-wide selectivity, especially when used in cells. Compound was designed as a negative control to be used alongside compound in experiments to interrogate CDKL2-mediated biology. A solved cocrystal structure of compound bound to CDKL2 highlighted key interactions it makes within its ATP-binding site. Inhibition of downstream phosphorylation of EB2, a CDKL2 substrate, in rat primary neurons provided evidence that engagement of CDKL2 by compound in cells resulted in inhibition of its activity. When used at relevant concentrations, compound does not impact the viability of rat primary neurons or certain breast cancer cells nor elicit consistent changes in the expression of proteins involved in epithelial-mesenchymal transition. - Source: PubMed
Publication date: 2024/07/03
Bashore Frances MMin Sophia MChen XiangrongHowell StefanieRinderle Caroline HMorel GabrielSilvaroli Josie AWells Carrow IBunnell Bruce ADrewry David HPabla Navjot SUltanir Sila KBullock Alex NAxtman Alison D