Ask about this productRelated genes to: PACSIN2 antibody
- Gene:
- PACSIN2 NIH gene
- Name:
- protein kinase C and casein kinase substrate in neurons 2
- Previous symbol:
- -
- Synonyms:
- SDPII
- Chromosome:
- 22q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-12
- Date modifiied:
- 2016-10-05
Related products to: PACSIN2 antibody
Related articles to: PACSIN2 antibody
- Major depressive disorder (MDD) is generally associated with synaptic damage in specific brain regions. However, the molecular mechanisms underlying the pathogenesis of MDD remain largely unknown. In the present study, we demonstrate that chronic stress-an established inducer of depression-like behaviors in animal models-upregulates the expression of protein kinase C and casein kinase substrate in neurons protein 2 (PACSIN2) in the hippocampal dCA1 region, a key regulator of the actin cytoskeleton and endocytic processes. The overexpression of PACSIN2 in CA1 hippocampal pyramidal neurons may increase the susceptibility to stress stimulation in rats through physical interactions with dynamin and cooperative modulation of the expression of postsynaptic membrane GluA1 AMPA receptors. Selective knockdown of PACSIN2 in the dCA1 hippocampal region of depressed rats significantly enhanced synaptic transmission, ultimately ameliorating depression-like behaviors. These findings provide direct evidence that abnormal function of hippocampal neurons resulting from perturbations in neuroplasticity may be involved in the pathogenesis of MDD. Moreover, PACSIN2 may serve as one of the underlying molecular controls through which chronic stress induces synaptic loss and dysfunction and the resulting behavioral disorders. - Source: PubMed
Publication date: 2026/05/07
Wang Chang-MinLi YeYi Yu-HangChen XiaoLan TianLou Hai-YanJian Wen-ChengWang Mei-JianYu Shu-Yan - Personalized thiopurine therapy is among the most established examples of pharmacogenomics translated into clinical practice. Variants in TPMT (rs1800462, rs1800460, rs1142345) and NUDT15 (rs116855232) are recognized clinical predictors of thiopurine efficacy and toxicity. Additional variants in genes such as PACSIN2 (rs2413739), ITPA (rs1127354) and MTHFR (rs1801133 and rs1801131), also contribute to variability in drug response. Here we characterize the frequency of the pharmacogenetic variants involved in thiopurine metabolism in a healthy population of Kosovo. We genotyped 299 healthy blood donors for polymorphisms. Among TPMT variant alleles, TPMT*3A was observed at a frequency of 2.0%, and the TPMT*3C at 0.1%. Notably, the MTHFR 677T variant (rs1801133) was significantly more frequent in the Kosovo population (49.8%) compared with the global and European frequencies. The minor allele frequency of MTHFR rs1801131 was 27.4%. Minor allele frequencies for PACSIN2 rs2413739 and ITPA rs1127354 variants were 48.8% and 4.0%, respectively. Sequencing of NUDT15 revealed six variants, with rs116855232 present at frequency of 0.8%. These findings provide important insights into the pharmacogenomic profile of the Kosovo population and support the implementation of pre-emptive genotyping to improve the safety and efficacy of thiopurine therapy in the region. - Source: PubMed
Publication date: 2026/02/27
Pasha FlakaUrbančič DunjaGosheva GordanaZhubi BukurijeMaliqi Qormemeti SafeteKrasniqi ShaipMlinarič-Raščan Irena - Thiopurines are effective drugs for inflammatory bowel disease, but their use is limited by side effects such as pancreatitis, whose mechanism remains unknown and may be more severe in children. This study investigated in a personalized way thiopurine-induced pancreatitis mechanism using induced pluripotent stem cells from pediatric inflammatory bowel disease patients. Ten pediatric patients, five developing pancreatitis (cases) and five without it (controls), were enrolled. Patient-specific stem cells and their pancreatic differentiated counterparts were used to evaluate thiopurine cytotoxicity, to quantify metabolites levels by liquid chromatography-tandem mass spectrometry, and to assess thiopurine pharmacodynamics by western-blot assay. Statistical analyses were performed applying Student's t-test or two-way ANOVA followed by Bonferroni's post-hoc test for multiple comparisons. Cytotoxicity assays revealed higher thioguanine cytotoxicity in stem and pancreatic cells from cases; pancreatic cells from cases were also more sensitive to mercaptopurine. Moreover, thioguanine treatment on stem cells produced thioguanosine monophosphate and its methylated form, but their concentration did not differ significantly between the groups. In addition, higher TPMT gene expression was observed in stem cells from cases, but no differences were observed in pancreatic cells. No significant differences were detected in HPRT, NUDT15, ITPA, or PACSIN2 expression. Lastly, Rac1 protein concentration was similar in stem cells from cases and controls, but pancreatic cells from cases exhibited significantly higher Rac1 expression. These findings suggest that thiopurine cytotoxicity differences might be linked to pharmacokinetics in stem cells, while altered Rac1 expression in pancreatic cells might contribute to pancreatitis, implicating distinct mechanisms between stem and differentiated cells. - Source: PubMed
Publication date: 2025/09/13
Rispoli PaolaGenova ElenaYue FengmingJohkura KoheiFranzin MartinaHofmann UteSchwab MatthiasFerraro Rosalba MonicaMazzoldi Elena LauraGiliani Silvia ClaraPiovani GiovannaBramuzzo MatteoMartelossi StefanoMiele ErasmoMartinelli MassimoMarchetti FedericoPelin MarcoDecorti GiulianaLucafò MariannaStocco Gabriele - Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis ( < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency ( < 0.01). Several of these genes were implicated in bone metabolism (e.g., , , ), vitamin D metabolism (e.g., , ), skeletal muscle function (e.g., , ), and reproductive processes (e.g., , , ). Notably, the rs783540 SNP exhibited the strongest association ( < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle-bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms. - Source: PubMed
Publication date: 2025/08/22
Kim Su KangHong Seoung-JinKim GyutaeBan Ju YeonKang Sang Wook - Azathioprine is used for inflammatory bowel disease (IBD) therapy. Patients under 6 years of age (very early onset, VEO-IBD) showed distinctive clinical characteristics, such as increased activity of thiopurine-methyltransferase (TPMT), a crucial enzyme for thiopurine metabolism. and polymorphisms were associated with azathioprine efficacy. This study investigated the role of age in thiopurine active metabolites and disease activity. Also, the effects of age, and polymorphisms on azathioprine metabolites and disease activity were evaluated. Erythrocytes thioguanine nucleotides (TGN) were measured by HPLC, and leukocytes incorporated deoxythioguanosine (DNA-TG) byLC-MS/MS in 12 VEO-IBD patients (median age 4.13 ± 0.98, 7 females, 6 Crohn's disease (CD)), 11 IBD children (median age 9.36 ± 1.52, 8 females, 1 CD ), and 73 IBD adolescents (median age 14.92 ± 1.81, 33 females, 37 CD). VEO-IBD subjects required a higher azathioprine dose (-value = 0.048) and showed a lower DNA-TG/azathioprine dose ratio (-value = 0.049) and TGN/azathioprine dose ratio (-value = 0.013). DNA-TG was positively correlated with TGN (-value = 4.15 × 10) and disease score (-value = 1.54 × 10). rs1142345 (76 wild type, 10 heterozygous) was associated with increased concentrations of DNA-TG and TGN (-value = 0.024 and 0.00038, respectively), whereas rs2413739 (37 wild types, 34 heterozygous, 16 homozygous variants) was associated with the disease score (-value = 0.04). Together, these data confirmed that VEO-IBD patients show enhanced azathioprine metabolism, which can be accurately reflected by both TGN and DNA-TG levels, highlighting their ability to be good biomarkers of azathioprine metabolism. - Source: PubMed
Publication date: 2025/06/05
Zudeh GiuliaFranzin MartinaLucafò MariannaBramuzzo MatteoCurci DeboraYang Jun JMaillard MaudDecorti GiulianaStocco Gabriele