Ask about this productRelated genes to: ADAM30 Blocking Peptide
- Gene:
- ADAM30 NIH gene
- Name:
- ADAM metallopeptidase domain 30
- Previous symbol:
- -
- Synonyms:
- svph4
- Chromosome:
- 1p12
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-23
- Date modifiied:
- 2019-03-22
Related products to: ADAM30 Blocking Peptide
Related articles to: ADAM30 Blocking Peptide
- Type 2 diabetes mellitus (T2DM) risk is heavily influenced by genetics, yet current association tests have explained only parts of its heritability. We developed MEVA (Meta-Evolutionary Action), a meta-analytic framework that integrates three complementary methods-EAML, Sigma-Diff, and GeneEMBED-to assess the functional burden of protein-coding variants using evolutionary data. MEVA was applied to exome data from 28,115 T2DM cases and 28,115 controls in the UK Biobank (UKB), identifying 101 genes (p < 1e-5). MEVA outperformed its component methods, each of which substantially outperformed a conventional burden test (MAGMA), in recovering known T2DM genes (AUROC = 0.925) and maintaining robustness in progressively smaller cohorts (AUROC = 0.917). MEVA showed significant enrichment for T2DM-related loci (p = 6.8e-10, p = 2.0e-34), protein interactions (z = 4.6, z = 4.2), pathways (p = 1.3e-6, z = 2.0), phenotypes (p = 1.3e-21, z = 9.1), and literature mentions (z = 7.2). Replication in 16,915 T2DM cases and 16,915 controls from All of Us (AoU) yielded 99 genes (p < 1e-5), 23 of which were also recovered in the UKB cohort - far exceeding random chance. These included established genes (SLC30A8, WFS1, HNF1A) and less-characterized candidates (NRIP1, ADAM30, CALCOCO2, TUBB1, ZFP36L2, WDR90). Notably, NRIP1 loss-of-function variants were associated with increased T2DM risk in both the UKB (OR = 1.09, FDR = 5.4e-4) and AoU (OR = 1.09, FDR = 0.046), and TUBB1 and CALCOCO2 gain-of-function variants showed consistent risk effects (FDR < 0.05). Pathway analyses revealed convergence on endoplasmic reticulum chaperone complexes (FDR = 0.02) and Hippo signaling (FDR = 8.5e-4). Finally, all 177 candidate genes were functionally prioritized using ten orthogonal criteria to guide experimental follow-up. These results demonstrate that combining complementary, impact-aware association tests increases sensitivity, improves replication, and expands the catalog of genetic risk factors for T2DM. - Source: PubMed
Publication date: 2025/09/30
Wilhelm KevinAsmussen JenniferLee KwanghyukSamieinasab MaryamAsante EmmanuelKimmel MarekLichtarge Olivier - DNA methylation plays a critical role in regulating gene expression during testicular development. However, few studies report on candidate genes related to the DNA methylation regulation of porcine testicular development. This study examined the differentially expressed genes (DEGs) and their methylation levels in testicular tissues from pigs at 60 days of age (60 d) and 180 days of age (180 d) using RNA-Seq and whole genome bisulfite sequencing (WGBS). It was determined that DNA methylation primarily occurs in the cytosine-guanine (CG) context, and the analysis identified 106,282 differentially methylated regions (DMRs) corresponding to 12,385 differentially methylated genes (DMGs). Further integrated analysis of RNA-Seq and WGBS data revealed 1083 DMGs negatively correlated with the expression of DEGs. GO analysis showed that these genes were significantly enriched in spermatogenesis, germ cell development, and spermatid differentiation. The screening of enriched genes revealed that hyper-methylation repressed , , , , , , , and , while hypo-methylation elevated , , , , and expression. Additionally, the methylation status of the key genes , , , , , and was detected by bisulfite sequencing PCR (BSP). This study offers insights into the epigenetic regulation mechanisms underlying porcine testicular development. - Source: PubMed
Publication date: 2024/08/22
Feng YueZhang YuWu JunjingQiao MuZhou JiaweiXu ZhongLi ZipengSun HuaPeng XianwenMei Shuqi - The DNA and RNA aptamers D4 and R4, respectively, emerged from the modification of PC-3 cell-binding aptamer A4. Our objective was to characterize the aptamers in silico and in vitro and begin to identify their target molecules. We represented their structures using computational algorithms; evaluated their binding to several prostate cell lines and their effects on the viability and migration of these cells; and determined their dissociation constant by flow cytometry. We analyzed circulating prostate tumor cells from patients using D4, R4, anti-CD133 and anti-CD44. Finally, the target proteins of both aptamers were precipitated and identified by mass spectrometry to simulate their in silico docking. The aptamers presented similar structures and bound to prostate tumor cells without modifying the cellular parameters studied, but with different affinities. The ligand cells for both aptamers were CD44, indicating that they could identify cells in the mesenchymal stage of the metastatic process. The possible target proteins NXPE1, ADAM30, and MUC6 need to be further studied to better understand their interaction with the aptamers. These results support the development of new assays to determine the clinical applications of D4 and R4 aptamers in prostate cancer. - Source: PubMed
Publication date: 2024/05/14
Campos-Fernández EstherAlqualo Nathalia OliveiraVaz Emília RezendeRodrigues Cláudia MendonçaAlonso-Goulart Vivian - As a widely distributed RNA methylation modification, m5C is involved in the regulation of tumorigenesis. Nevertheless, its fundamental process is not clear. This research sought to examine the genetic properties of the 5-methylcytosine (m5C) regulator in endometrial carcinoma, as well as the prognostic significance and impact of m5C regulators on oxidative stress. Therefore, the TCGA-UCEC data set was used to explore the characteristics of 17 RNAm5C-related genes in the transcriptome, genome, and regulatory network. The subtypes of RNAm5C in UCEC were identified based on the expression levels of 17 RNAm5C-related genes. The prognosis of RNAm5C-2 was significantly better than that of RNAm5C-1. Then, we examined the differences (variations) across various subtypes in terms of immune cell infiltration (ICI) as well as the expression of immune-related signal markers. The findings demonstrated that there were distinct variations in the infiltration level of immune cells in each subtype, which may be the reason for the differences in the prognosis of each subtype. In addition, the differentially expressed genes (DEGs) among RNAm5C subtypes of different UCEC tumors were identified, and the DEGs significant for survival were screened. After obtaining 34 prognostic genes, the dimensionality was reduced to construct an RNA methylation score (RS). As per the findings, RS is a more accurate marker for determining the prognosis for patients with endometrial cancer. The RS was used to categorize UCEC tumor samples, and these results led to the formation of high-score and low-score groups. The patients in the group with a high-RNA methylation score exhibited a survival time that was considerably longer in contrast with those in the group with a low-RNA methylation score. The capacity of RS to predict whether or not immunotherapy would be beneficial was explored further. In the group with a high-RNA methylation score, the objective response rate to the anti-PD-L1 therapy was substantially greater compared to that observed in the subgroup with a low-RNA methylation score. Additionally, there were variations across various RS groups in terms of clinical features, tumor mutation burden, and the infiltration level of immune cells. After binary tree analysis and PCR verification of 34 prognostic genes, it is finally found that the six genes of MAGOH3P, TRBJ2_3, YTHDF1P1, RP11_323D18.5, RP11_405M12.2, and ADAM30 are significantly overexpressed in cancer tissues. These genes can be used as potential biomarkers of endometrial cancer and provide data support for precise immunotherapy in UCEC tumors. - Source: PubMed
Publication date: 2022/09/21
Dong ChunliDang LingGao XiaocuiXu RenyanZhang HuiZhang Xin - Identifying the molecular underpinnings of the neural specializations that underlie human cognitive and behavioral traits has long been of considerable interest. Much research on human-specific changes in gene expression and epigenetic marks has focused on the prefrontal cortex, a brain structure distinguished by its role in executive functions. The cerebellum shows expansion in great apes and is gaining increasing attention for its role in motor skills and cognitive processing, including language. However, relatively few molecular studies of the cerebellum in a comparative evolutionary context have been conducted. Here, we identify human-specific methylation in the lateral cerebellum relative to the dorsolateral prefrontal cortex, in a comparative study with chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta). Specifically, we profiled genome-wide methylation levels in the three species for each of the two brain structures and identified human-specific differentially methylated genomic regions unique to each structure. We further identified which differentially methylated regions (DMRs) overlap likely regulatory elements and determined whether associated genes show corresponding species differences in gene expression. We found greater human-specific methylation in the cerebellum than the dorsolateral prefrontal cortex, with differentially methylated regions overlapping genes involved in several conditions or processes relevant to human neurobiology, including synaptic plasticity, lipid metabolism, neuroinflammation and neurodegeneration, and neurodevelopment, including developmental disorders. Moreover, our results show some overlap with those of previous studies focused on the neocortex, indicating that such results may be common to multiple brain structures. These findings further our understanding of the cerebellum in human brain evolution. - Source: PubMed
Publication date: 2021/05/06
Guevara Elaine EHopkins William DHof Patrick REly John JBradley Brenda JSherwood Chet C