更新于：2024-11-01

PGAP3

更新于：2024-11-01

基本信息

别名

CAB2、COS16 homolog、Gene coamplified with ERBB2 protein

+ [9]

简介

Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchors proteins. Required for phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI.

关联

PGAP3靶向基因疗法(Nationwide Children's Hospital)

靶点

PGAP3

作用机制

PGAP3 modulators [+1]

在研机构

Nationwide Children's Hospital [+1]

原研机构

Nationwide Children's Hospital [+1]

在研适应症

先天性糖基化障碍

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PGAP3 相关的临床结果

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100 项与 PGAP3 相关的转化医学

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0 项与 PGAP3 相关的专利（医药）

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项与 PGAP3 相关的文献（医药）

2024-08-01·eBioMedicine

Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism

Article

作者: Tang, Weihong ; Psaty, Bruce ; Smith, Nicholas ; Nielsen, Jonas ; Wiggins, Kerri ; Tan, Marcus C.B. ; Giulianini, Franco ; Ridker, Paul ; Chasman, Daniel ; Ibrahim, Manal ; Pankratz, Nathan ; De Andrade, Mariza ; Heckbert, Susan ; Taylor, Kent ; MacDonald, James ; Lindstrom, Sara ; Suchon, Pierre ; Haessler, Jeffrey ; Pankow, James ; Hveem, Kristian ; Johnson, Andrew ; O'Donnell, Chris ; McKnight, Barbara ; Deleuze, Jean-François ; Turman, Constance ; Wang, Lu ; Van Hylckama Vlieg, Astrid ; Heit, John ; Hansen, John-Bjarne ; Gamazon, Eric R. ; Kooperberg, Charles ; Morange, Pierre-Emmanuel ; Gordon, William ; Armasu, Sebastian ; McCauley, Bryan ; Frazer, Kelly ; Brumpton, Ben ; Brody, Jennifer ; Rosendaal, Frits ; Braekkan, Sigrid ; Germain, Marine ; Chen, Ming-Huei ; Bammler, Theo ; Liu, Yangzi ; Reiner, Alexander ; Puurunen, Marja ; Kim, Jihye ; Gabrielsen, Maiken ; Wu, Lang ; Zhou, Dan ; Trégouët, David-Alexandre ; Isom, Chelsea A. ; Smith, Erin ; Pattee, Jack ; Jackson, Rabecca ; Kraft, Peter ; Kabrhel, Christopher

BACKGROUNDTwo important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE).METHODSIn this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls).FINDINGSSixteen genes showed an association with PDAC risk (FDR <0.10), including six genes not yet reported for PDAC risk (PPIP5K2, TFR2, HNF4G, LRRC10B, PRC1 and FBXL20) and ten previously reported genes (INHBA, SMC2, ABO, PDX1, MTMR6, ACOT2, PGAP3, STARD3, GSDMB, ADAM33). MR provided support for a causal effect of PDAC on T2D using genetic instruments in the HNF4G and PDX1 loci, and unidirectional causality of VTE on PDAC involving the ABO locus (OR 2.12, P < 1e^-7). No evidence of a causal effect of PDAC on VTE was found.INTERPRETATIONThese analyses identified candidate susceptibility genes and disease relationships for PDAC that warrant further investigation. HNF4G and PDX1 may induce PDAC-associated diabetes, whereas ABO may induce the causative effect of VTE on PDAC.FUNDINGNational Institutes of Health (USA).

2024-07-19·Briefings in Functional Genomics

Integrating multi-omics data to analyze the potential pathogenic mechanism of CTSH gene involved in type 1 diabetes in the exocrine pancreas

Article

作者: Meng, Xin ; Cheng, Xiangshu ; Zhang, Shuhao ; Li, Shuai ; Chen, Rui ; Zhang, Ruijie ; Song, Zerun ; Shang, Zhenwei ; Lv, Wenhua

AbstractType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of insulin-producing pancreatic islet beta cells. Despite significant advancements, the precise pathogenesis of the disease remains unknown. This work integrated data from expression quantitative trait locus (eQTL) studies with Genome wide association study (GWAS) summary data of T1D and single-cell transcriptome data to investigate the potential pathogenic mechanisms of the CTSH gene involved in T1D in exocrine pancreas. Using the summary data–based Mendelian randomization (SMR) approach, we obtained four potential causative genes associated with T1D: BTN3A2, PGAP3, SMARCE1 and CTSH. To further investigate these genes’roles in T1D development, we validated them using a scRNA-seq dataset from pancreatic tissues of both T1D patients and healthy controls. The analysis showed a significantly high expression of the CTSH gene in T1D acinar cells, whereas the other three genes showed no significant changes in the scRNA-seq data. Moreover, single-cell WGCNA analysis revealed the strongest positive correlation between the module containing CTSH and T1D. In addition, we found cellular ligand–receptor interactions between the acinar cells and different cell types, especially ductal cells. Finally, based on functional enrichment analysis, we hypothesized that the CTSH gene in the exocrine pancreas enhances the antiviral response, leading to the overexpression of pro-inflammatory cytokines and the development of an inflammatory microenvironment. This process promotes β cells injury and ultimately the development of T1D. Our findings offer insights into the underlying pathogenic mechanisms of T1D.

2024-07-01·Molecular Genetics & Genomic Medicine

A case of inherited glycosylphosphatidylinositol deficiency caused by PGAP3 variant with uniparental isodisomy on chromosome 17

Article

作者: Takami, Hirokazu ; Kitaoka, Hiroki ; Kato, Motohiro ; Shitara, Yoshihiko ; Ito, Atsushi ; Mukai, Takeo ; Takahashi, Naoto ; Kashima, Kohei ; Kuroda, Yukiko ; Kato, Shota ; Tanaka, Hiroyuki

AbstractBackgroundInherited glycosylphosphatidylinositol (GPI) deficiency is an autosomal recessive disease and a set of syndromes caused by different genes involved in the biosynthesis of phosphatidylinositol characterized by severe cognitive disability, elevated serum alkaline phosphatase (ALP) levels, and distinct facial features. This report presents a patient with inherited GPI deficiency caused by a homozygous frameshift variant of PGAP3 due to uniparental isodisomy (UPiD) on chromosome 17.MethodClinical characteristics of the patient were collected. Microarray analysis followed by adaptive sampling sequencing targeting chromosome 17 was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region.ResultsThe patient was born at 38 weeks of gestation with a birthweight of 3893 g. He had a distinctive facial appearance with hypertelorism, wide nasal bridge, and cleft soft palate. Postnatal head magnetic resonance imaging revealed a Blake's pouch cyst. The serum ALP level was 940 IU/L at birth and increased to 1781 IU/L at 28 days of age. Microarray analysis revealed region of homozygosity in nearly the entire region of chromosome 17, leading to the diagnosis of UPiD. Adaptive sampling sequencing targeting chromosome 17 confirmed the homozygous variant NM_033419:c.778dupG (p.Val260Glyfs*14) in the PGAP3 gene, resulting in a diagnosis of inherited GPI deficiency.ConclusionThis is the first report of inherited GPI deficiency caused by UPiD. Inherited GPI deficiency must be considered in patients with unexplained hyperphosphatasemia.

项与 PGAP3 相关的新闻（医药）

2024-02-22

·今日头条

再取进展！南京医科大学何帮顺/王书奎团队揭示乳腺癌进展新机制及治疗新靶点

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：乳腺癌(BC)是世界范围内女性最常见的恶性肿瘤。尽管早期发现和治疗策略的显著进步导致死亡率下降，但复发和转移仍然是BC患者癌症死亡的主要原因。 2月20日，南京医科大学何帮顺/王书奎研究团队在期刊《Cell Death&Disease》上发表了题为“Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription”的研究论文，本研究中，研究表明hsa_circ_0007990调节YBX1蛋白的泛素化和降解，并进一步调节E2F1的表达，促进BC的进展。研究人员探索了hsa_circ_0007990在BC中的可能功能和分子机制，并确定了一种新的治疗BC的候选靶点。 https://www.nature.com/articles/s41419-024-06527-7#Sec2 研究背景 01 乳腺癌(BC)已成为世界上最常见的癌症。近年来，由于早期发现和治疗的改善，BC的死亡率显著下降。然而，复发和转移仍然频繁发生，并继续威胁生存。由于对BC发展的分子机制知之甚少，需要进一步的研究来发现新的致病因素和治疗靶点。环状RNA (circRNAs)是一类特殊的RNA，具有共价封闭的单链环状结构。大量研究表明，环状RNA是高度保守、稳定和丰富的，并表现出疾病和组织特异性表达模式，这使它们能够在包括癌症在内的多种疾病中发挥重要的生物学功能。越来越多的证据表明，失调的环状RNA，如胃癌抑制因子circMTHFD2L，结直肠癌进展促进因子circINSIG1和BC过表达的circPVT1，可以作为致癌和肿瘤抑制因子。此外，据报道，circRNAs通过各种调节机制参与癌症的发病机制。尽管circRNAs的研究已经取得了一些进展，但circRNAs在BC肿瘤发生中的作用以及所涉及的详细分子机制还有待进一步阐明。研究进展 02 为探索hsa_circ_0007990在BC中的潜在生物学功能，研究人员设计了针对hsa_circ_0007990后接连接位点的两个敲低序列，并通过慢病毒转导到MCF-7细胞中。通过慢病毒介导的转导，在MDA-MB-231细胞中构建hsa_circ_0007990过表达载体，验证了hsa_circ_0007990的过表达效率。然后进行功能实验观察BC细胞的生物学行为。CCK8实验显示，敲低hsa_circ_0007990显著抑制MCF-7细胞的增殖，而过表达hsa_circ_0007990显著增加MDA-MB-231细胞的增殖。集落形成实验进一步支持了这些结果。此外，EdU实验表明，在MCF-7细胞中，沉默hsa_circ_0007990可抑制DNA合成，而在MDA-MB-231细胞中，上调hsa_circ_0007990则产生相反的效果。综上所述，这些体外实验表明hsa_circ_0007990可以促进BC细胞的生长。为了进一步研究hsa_circ_0007990在体内对BC细胞生长的影响，研究人员进行了裸鼠移植瘤实验。如图1A-C所示，与对照组相比，hsa_circ_0007990敲低组的异种移植瘤表现出较慢的生长速度和较低的肿瘤重量。不出所料，hsa_circ_0007990过表达组的肿瘤表现出相反的效果。免疫组织化学染色结果显示，hsa_circ_0007990敲低组细胞增殖标志物Ki67表达降低。因此，这些结果表明，hsa_circ_0007990可以促进BC细胞在体内的生长。图1：Hsa_circ_0007990可促进BC在体内的生长研究结论 03 综上所述，本研究鉴定并表征了一个新的circRNA hsa_circ_0007990，它在BC细胞中部分由于宿主基因PGAP3的扩增而上调。结果还显示，hsa_circ_0007990在BC组织中过表达，并与BC患者的恶性进展相关，但由于样本量较小，差异不显著。功能上，hsa_circ_0007990在体外和体内均促进BC的增殖和成瘤。机制上，hsa_circ_0007990与YBX1相互作用，抑制其泛素化和降解，进而促进E2F1转录。本研究阐明了hsa_circ_0007990在乳腺癌中的可能作用，为乳腺癌的治疗提供了一个有前景的治疗靶点。参考资料： https://www.nature.com/articles/s41419-024-06527-7#Sec2 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

临床研究临床结果