Ask about this productRelated genes to: VPS53 antibody
- Gene:
- VPS53 NIH gene
- Name:
- VPS53 subunit of GARP complex
- Previous symbol:
- -
- Synonyms:
- FLJ10979, HCCS1
- Chromosome:
- 17p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-11-29
- Date modifiied:
- 2019-01-25
Related products to: VPS53 antibody
Related articles to: VPS53 antibody
- Ionizing radiation is a confirmed independent environmental factor for thyroid cancer. Environmental and occupational exposure are exposed to low-dose ionizing radiation (LDR), which underscores the persistent need to decipher the mechanisms of LDR induced thyroid carcinogenesis. In addition to the canonical driver mutations or chromosomal rearrangements, there remains a gap in understanding the key drivers of LDR-induced thyroid cancer that needs to be clarified. VPS53, a core subunit of the Golgi-associated retrograde protein (GARP) complex, mediates retrograde vesicular trafficking, but its role in LDR-induced thyroid tumorigenesis is uncharacterized. Here, we found that LDR induces an increase in VPS53 copy number in clones of thyroid follicular epithelial cell malignant transformation, leading to elevated expression levels, and high VPS53 expression is associated with poor prognosis in thyroid cancer patients. Functionally, VPS53 promotes the proliferation and clonal formation of thyroid cancer cells; meanwhile, xenograft tumor experiments in nude mice demonstrated that high expression of VPS53 facilitates tumor growth. Mechanistically, VPS53 directly interacts with EGFR, redirecting it from the lysosomal degradation pathway to the plasma membrane recycling pathway, thereby maintaining the sustained activation of the carcinogenesis signaling pathway. Moreover, VPS53 alters the direction of DNA double-strand break repair, favoring non-homologous end joining (NHEJ) over homologous recombination (HR), which exacerbates genomic instability. These mechanisms collectively promote the thyroid carcinogenesis. Collectively, we have confirmed a novel mechanism by which the VPS53-EGFR axis drives thyroid carcinogenesis induced by LDR, and provided new insights into thyroid tumor biology. - Source: PubMed
Publication date: 2026/07/01
Liu YuhaoZhou LinZhu JiaojiaoAo XingkunWang PingYan ZiyanChen HuixiZhang XinyuYe MengchanLuan ShuhuaGu YongqingZhou Ping-Kun - Ruminant meat is an important component of human diets, valued for its unique flavor and nutritional density. Lipids play a dominant role in shaping meat flavor, yet their genetic and biochemical basis remains unexplored. Here, from the analysis of 434 sheep longissimus thoracis samples, the current study presents the first comprehensive lipid map of sheep meat, including 947 lipids. A substantial proportion of these lipids exhibit moderate-to-high heritability, with 51.6% surpassing a heritability of 0.2 and 15.8% exceeding 0.45. Metabolome-based genome-wide association analysis identifies 467 significant loci affecting 233 lipids, including 110 loci exhibiting pleiotropy. Notably, the levels of monogalactosyldiacylglycerols containing oleic (C18:1) and linoleic (C18:2) acids are specifically regulated by the expression of MBOAT1 and PAQR8 genes, respectively, while 13 triglycerides and one diglyceride are co-regulated by SH2D4A. The levels of phosphatidylethanolamine PE(20:4_20:0) are regulated by VPS53. Further examination of volatile compounds demonstrates that variations in these genetically controlled lipids significantly impact flavourant levels in cooked meat. Given the conservation of lipid profiles and genomes among ruminants, this study offers novel insights into the genetic architecture underlying meat lipid metabolism and provides a valuable resource for the targeted genetic improvement of ruminant meat flavor. - Source: PubMed
Publication date: 2025/08/11
Zhang XueyingKong YuanyuanChen JialeiLi RanWang ZhongyuSong YaliDai TianshuFu YuxinJiang BeixiangZeng JizePei ShengweiLiu YangkaiFeng QianjieFu WeiweiYuan ZehuMwacharo Joram MwashigadiLi FadiYue Xiangpeng - Mature B-cell acute lymphocytic leukaemia (B-ALL) is distinguished from B-cell non-Hodgkin lymphoma (B-NHL) by the arbitrariness of the 25% cut-off, and given that the percentage of bone marrow (BM) blasts can vary according to site of aspirate, we refrained from differentiating mature B-ALL from B-NHL with BM infiltration. A total of 156 patients from the Chinese Children Cancer Group with BM blasts of more than 5% and consistent with immunophenotypic features of mature B cells were included in this study. The 2-year progression-free survival, 2-year event-free survival and 2-year overall survival were 76.6 ± 3.6%, 69.7 ± 3.7% and 80.1 ± 3.3% respectively. Central nervous system (CNS) involvement, serum ferritin levels higher than four times normal and rituximab no more than two doses were associated with lower PFS. Male, bulky disease and head/neck region involvement were associated with higher rate of CNS invasion. We performed an integrative transcriptomic characterization of 36 cases. Structure variant included IG::MYC, IGH::CACS11, MEF2D::BCL9, IGH::VPS53 and ACIN1::NUTM1. SNV analysis uncovered driver variations affecting 10 recurrently mutated genes including ID3, TP53, MYC, ARID1A, SMARCA4, DDX3X, CCND3, RHOA, SMARCB1, FOXO1 and GNA13. Mature B-ALL/B-NHL with BM involvement was a heterogeneous group of malignancies in both clinical features and genetic alternations. Genetics analysis was helpful for making accurate diagnoses and guiding appropriate therapeutic strategies. - Source: PubMed
Publication date: 2025/02/17
Zhao JieLiu Tian-FengWu Ke-FeiYang Liang-ChunXu Xue-JuLu JunShao Jing-BoLi FuMa Fu-TianGuo XiaLi HuiLiu Ai-GuoWang Ning-LingShen He-PingLi YangLiu Si-XiLiang Chang-DaShen Shu-HongFang Yong-JunGao Yi-Jin - Pathogenic variants in VPS53 are associated with pontocerebellar hypoplasia type 2E (PCH2E), characterized by microcephaly, severe neurodevelopmental impairment and epilepsy. We present a case of a female neonate with VPS53 pathogenic variants exhibiting the classic phenotypic features along with liver disease and deafness, which had not been described in previously reported cases. Similarly, while liver abnormalities have been reported in patients with mutations in other genes coding for proteins of the GARP or EARP complex, of which VPS53 is a subunit, liver disease has not been described in PCH2E until now. This case suggests that liver involvement may be an under-recognized feature of PCH2E and, more broadly, in GARP or EARP dysfunction, warranting further investigation. - Source: PubMed
Publication date: 2025/01/20
Mouchez AurianeHoebeke CéliaDesnous BéatriceCano AlineFritih RadiaFabre Alexandre - While genome-wide association studies and expression quantitative trait loci (eQTL) analysis have made significant progress in identifying noncoding variants associated with prostate cancer risk and bulk tissue transcriptome changes, the regulatory effect of these genetic elements on gene expression remains largely unknown. Recent developments in single-cell sequencing have made it possible to perform ATAC-seq and RNA-seq profiling simultaneously to capture functional associations between chromatin accessibility and gene expression. In this study, we tested our hypothesis that this multiome single-cell approach allows for mapping regulatory elements and their target genes at prostate cancer risk loci. We applied a 10X Multiome ATAC + Gene Expression platform to encapsulate Tn5 transposase-tagged nuclei from multiple prostate cell lines for a total of 65,501 high quality single cells from RWPE1, RWPE2, PrEC, BPH1, DU145, PC3, 22Rv1 and LNCaP cell lines. To address data sparsity commonly seen in the single-cell sequencing, we performed targeted sequencing to enrich sequencing data at prostate cancer risk loci involving 2,730 candidate germline variants and 273 associated genes. Although not increasing the number of captured cells, the targeted multiome data did improve eQTL gene expression abundance by about 20% and chromatin accessibility abundance by about 5%. Based on this multiomic profiling, we further associated RNA expression alterations with chromatin accessibility of germline variants at single cell levels. Cross validation analysis showed high overlaps between the multiome associations and the bulk eQTL findings from GTEx prostate cohort. We found that about 20% of GTEx eQTLs were covered within the significant multiome associations (-value ≤ 0.05, gene abundance percentage ≥ 5%), and roughly 10% of the multiome associations could be identified by significant GTEx eQTLs. We also analyzed accessible regions with available heterozygous SNP reads and observed more frequent association in genomic regions with allelically accessible variants ( = 0.0055). Among these findings were previously reported regulatory variants including rs60464856-multiome -value = 0.0099 in BPH1) and rs7247241-multiome -value = 0.0002- 0.0004 in 22Rv1). We also functionally validated a new regulatory SNP and its target gene rs2474694-multiome -value = 0.00956 in BPH1 and 0.00625 in DU145) by reporter assay and SILAC proteomics sequencing. Taken together, our data demonstrated the feasibility of the multiome single-cell approach for identifying regulatory SNPs and their regulated genes. - Source: PubMed
Publication date: 2024/06/21
Tian YijunWu LangHuang Chang-ChingWang Liang