Ask about this productRelated genes to: VPS33A antibody
- Gene:
- VPS33A NIH gene
- Name:
- VPS33A core subunit of CORVET and HOPS complexes
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-13
- Date modifiied:
- 2019-01-25
Related products to: VPS33A antibody
Related articles to: VPS33A antibody
- Autophagy-mitophagy pathways are essential for regulating immune homeostasis. However, their contribution to population-level chronic low-grade systemic inflammation (SI) remains unclear. The objective was to investigate the association between variation in the genes related to the autophagy-mitophagy pathways and SI, and to examine whether lifestyle factors modify this relationship. We conducted genome-wide association studies and gene-set enrichment analyses using data from the Korean Genome and Epidemiology Study (KoGES, n = 28,102) and UK Biobank (UKBB, n = 343,892). SI was defined as an elevated white blood cell count or high-sensitivity C-reactive protein. Using Core Longevity State Vectors (CLSVs)-gene sets representing immune-longevity pathways derived from comparative transcriptomic analysis-we tested six pathways and constructed a weighted genetic risk score (GRS) from significant variants. Gene-lifestyle interactions were examined with respect to major dietary and lifestyle factors. Among six CLSVs, only CLSV-2 (mitophagy and autophagy) showed a significant association with SI (β = 0.425, = 0.008). Six single nucleotide polymorphisms (SNPs) in autophagy-mitophagy genes (, , , , , and ) were associated with SI in KoGES ( < 5 × 10), and ten SNPs (genes selected in KoGES plus , , , ) reached genome-wide significance in UKBB ( < 5 × 10). A higher GRS was associated with increased SI in both cohorts and was strongly associated with metabolic syndrome (MetS, OR = 1.91 in KoGES; OR = 1.62 in UKBB). SI was characterized by neutrophilia with relative lymphopenia. In UKBB, significant gene-lifestyle interactions were observed for diet, physical activity, smoking, and alcohol ( < 0.01). Favorable lifestyle factors reduced SI most effectively in individuals with protective genotypes. Among individuals with a high vegetable/fruit intake, SI prevalence was 35%, 36%, and 38% in the negative-, zero-, and positive-GRS groups, respectively, compared with 36%, 45%, and 48% in the low-intake groups. In conclusion, genetic variations in autophagy-mitophagy pathways specifically influence SI. Genetic predisposition substantially modifies the benefits of lifestyle, underscoring the importance of integrating genetic and lifestyle factors in understanding SI susceptibility. - Source: PubMed
Publication date: 2026/03/27
Choi YoungjinPark Sunmin - Pemigatinib, the inaugural FDA-approved targeted therapy for cholangiocarcinoma (CCA), represents a major advancement in the treatment of this malignancy. Nevertheless, the inevitable emergence of acquired resistance highlights an urgent need for innovative strategies to address this clinical challenge. This study investigates the role of VPS33A in modulating autophagy to mediate Pemigatinib resistance in CCA. - Source: PubMed
Publication date: 2026/02/20
Chen MengyuLuo ManZhang BolinXiao XinXu YushiWu FanggenZhou WeiLu Shan - Mucopolysaccharidosis-plus syndrome (MPS plus or MPSPS) is an ultrarare inherited metabolic disease, caused by mutations in the VPS33A gene. Like in different types of mucopolysaccharidosis (MPS), glycosaminoglycan (GAG) storage in cells of patients is evident. However, unlike MPS, the genetic defects in MPSPS cause impairment in the VPS33A protein level rather than inactivation of lysosomal hydrolases responsible for GAG degradation. Recent works demonstrated that low abundance of mutated VPS33A causes defective endosomal trafficking, resulting in poor delivery of GAGs (and perhaps also other compounds) to lysosomes, preventing their effective turnover. Here, we tested the hypothesis that impairment of protein degradation machineries, proteasomes by genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) and endoplasmic-reticulum-associated protein degradation (ERAD) by ambroxol (4-((2-amino-3,5-dibromophenyl)methylamino) cyclohexan-1-ol), might result in elevation of levels of the mutated, partially active VPS33A and improvement of cellular functions. Using a line of MPSPS patient-derived fibroblasts, we demonstrated that treatment with genistein and ambroxol resulted in elevation of the mutant VPS33A protein level, as well as in improvement or correction of various previously reported cellular defects, including GAG levels, endosomal markers, and cytoskeleton elements. In the light of these results, and since both genistein and ambroxol were previously demonstrated to be safe when used in relatively high amounts, we suggest that the use of these compounds, and especially their combination, might be considered as a potential therapeutic approach in MPSPS, which is currently an incurable disease. - Source: PubMed
Publication date: 2025/11/27
Cyske ZuzannaRintz EsteraGaffke LidiaPierzynowska KarolinaWęgrzyn Grzegorz - The classification of mucopolysaccharidoses (MPSs) includes the classical types (I; II; III with subtypes A, B, C, and D; IV with subtypes A and B; VI; VII; IX; X), associated with impaired lysosomal degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs), as a result of deficiency in the specific enzymes responsible for GAG degradation (MPS IIIE has so far been identified only in animal models) and MPS-plus syndrome (MPSPS), which is characterized by an accumulation of undegraded GAGs, arising from impaired endosomal trafficking and inefficient delivery of these compounds to lysosomes (due to the VPS33A protein deficiency with normal GAG-degrading enzyme activities assessed in vitro). The aim of this comprehensive review is to provide physicians with a clinical, biochemical, and molecular overview of MPS manifestation. A brief summary of available and emerging therapies is also presented. - Source: PubMed
Publication date: 2025/10/14
Lipiński PatrykRóżdżyńska-Świątkowska AgnieszkaWiśniewska KarolinaRusecka JoannaŁugowska AgnieszkaŻuber ZbigniewJezela-Stanek AleksandraCyske ZuzannaGaffke LidiaPierzynowska KarolinaWęgrzyn GrzegorzTylki-Szymańska Anna - Renin is mainly stored in the renin granules (RGs) of juxtaglomerular cells (JGCs). RGs are a type of lysosome-related organelle (LRO), and knowledge on the underlying mechanism of RG biogenesis is limited. Hermansky-Pudlak syndrome (HPS) is characterized by multiple LRO defects. Whether there are RG defects in HPS is unknown. Using different mouse models of HPS, we found that the active renin content was reduced in the kidneys of buff (bf) mice, which carry a homozygous point mutation (D251E) of Vps33a, a subunit of the HOPS complex. We observed that bf mice exhibited smaller RGs than did heterozygous mice. Knockdown of Vps33a, Snap23, Stx11 and Vamp8 in As4.1 cells impaired the biogenesis of RGs. Interaction between mutant Vps33aD251E and Stx11 was enhanced. We concluded that Vps33a is likely to be involved in the fusion process during RG biogenesis, which is regulated by the SNARE complex (Snap23-Stx11-Vamp8). The enhanced interaction of Vps33aD251E-Stx11 might impair the function of the SNARE complex, which is required for RG biogenesis. This highlights that defects in RG biogenesis can lead to hyporeninemia. - Source: PubMed
Publication date: 2025/09/25
Wang HuipengHao ZhenhuaLi Wei