Last update 01 Nov 2024

PGAP3

Last update 01 Nov 2024

Basic Info

Synonyms

CAB2, COS16 homolog, Gene coamplified with ERBB2 protein

+ [9]

Introduction

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.

Drugs associated with PGAP3

PGAP3-targeting gene therapy (Nationwide Children's Hospital)

Target

PGAP3

Mechanism

PGAP3 modulators [+1]

Active Org.

Nationwide Children's Hospital [+1]

Originator Org.

Nationwide Children's Hospital [+1]

Active Indication

Congenital Disorders of Glycosylation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGAP3

100 Translational Medicine associated with PGAP3

0 Patents (Medical) associated with PGAP3

Literatures (Medical) associated with PGAP3

01 Aug 2024·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

Author: 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).

19 Jul 2024·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

Author: 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.

01 Jul 2024·Molecular Genetics & Genomic Medicine

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

Article

Author: 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.

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PGAP3

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