Ask about this productRelated genes to: AGPAT2 Blocking Peptide
- Gene:
- AGPAT2 NIH gene
- Name:
- 1-acylglycerol-3-phosphate O-acyltransferase 2
- Previous symbol:
- BSCL
- Synonyms:
- LPAAT-beta
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-07
- Date modifiied:
- 2019-04-17
Related products to: AGPAT2 Blocking Peptide
Related articles to: AGPAT2 Blocking Peptide
- Congenital Generalized Lipodystrophy (CGL), usually caused by pathogenic variants in AGPAT2 (CGL1) and BSCL2 (CGL2), is characterized by near-total loss of subcutaneous adipose tissue, low leptin levels and severe metabolic and systemic comorbidities. Skeletal abnormalities including diffuse sclerosis, lytic-appearing bone lesions, and high bone mineral density have been recognized in CGL, but the prevalence and clinical and radiological features of these bone phenotypes remain ill-defined. The aim of this single-institution case series and systematic review was to evaluate bone manifestations and radiological findings associated with CGL1 and CGL2. Data sources were PubMed, Scopus, Embase, CINAHL Plus, Global Index Medicus, Web of Science: Core, National Institutes of Health medical records. Articles were screened utilizing a dual reviewer process in Covidence. Included publications reported primary bone and radiologic findings in patients with CGL1 or CGL2. Two reviewers extracted data using REDCap and assessed risk of bias. 43 articles were included in the review, presenting 214 cases of CGL (90 CGL1, 81 CGL2, and 43 genetics not reported). Data from NIH patients was extracted by retrospective chart review. The NIH cohort had 60 CGL patients (40 CGL1, 20 CGL2). Skeletal imaging included radiographs, MRI, CT, and NaF PET scans. In the literature and NIH cases, respectively, diffuse osteosclerosis was reported in 37% and 39%, lytic-appearing lesions in 64% and 53%, and high bone mineral density in 68% and 43%. Individuals with CGL1 and CGL2 present with distinct and heterogeneous bone phenotypes including lytic-appearing lesions primarily affecting long bones, diffuse osteosclerosis, and high bone mineral density. These bone manifestations are often overlooked despite high prevalence and clinical relevance. Potential mechanisms include increased differentiation of bone marrow mesenchymal cells into osteocytes and effects of increased insulin or decreased leptin signaling. - Source: PubMed
Publication date: 2026/06/13
Dyer M MahlonTuska Rebecca MBrush Maiah NLivinski Alicia MLebenthal YaelYao LawrenceFerreira Carlos RCollins Michael TBrown Rebecca J - Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the primary histological subtypes of cervical cancer. Although the AGPAT family of enzymes is implicated in various cancer types, the specific roles of its members in cervical cancer remain unclear. In the present study, we investigated the value of AGPAT1-5 as potential biomarkers and therapeutic targets in cervical cancer by assessing their impact on disease development and outcomes. AGPAT gene expression data and clinical information from 306 patients with CESC and three control subjects were collected from The Cancer Genome Atlas. Given the limited number of normal cervical samples in TCGA (n = 3), we utilized the GEPIA database to integrate GTEx normal cervical samples (n = 10) as controls for differential expression analysis. These data were analyzed for differential gene expression, gene-gene and protein-protein interactions, prognostic and diagnostic value, clinical correlations, functional enrichment, and various tumor-infiltrating immune cell types. Validation was performed using two independent Gene Expression Omnibus (GEO) datasets (GSE6791 and GSE63514). The study revealed that AGPAT4 mRNA expression was significantly downregulated in cervical cancer tissues compared to normal tissues in the GEPIA analysis, while AGPAT1, AGPAT2, AGPAT3, and AGPAT5 showed no significant differences. Validation in GEO datasets demonstrated that AGPAT1, AGPAT2, and AGPAT3 were consistently downregulated in tumor tissues, whereas AGPAT5 was upregulated, and AGPAT4 showed no significant change. High levels of AGPAT3 and AGPAT4 expression, in particular, were associated with a worse prognosis in CESC patients. Immune infiltration analysis restricted to CESC samples revealed that AGPAT3 expression was significantly correlated with multiple immune cell types, including positive correlations with Macrophages M1, T cells CD4 memory resting, and Monocytes. Furthermore, guided by functional enrichment analysis implicating immune-related pathways, we examined the correlation between AGPAT3 expression and key T cell regulatory molecules, including FOXP3, IL2RA, IKZF2, and CCR8, revealing significant positive associations. In vitro assays demonstrated that knocking out AGPAT3 expression significantly decreased the proliferation and migration of HeLa and C-33 A cervical cancer cell line. These results suggest that AGPAT3 could be a valuable biomarker and a promising therapeutic target in cervical cancer. - Source: PubMed
Publication date: 2026/06/09
Gui NannanPan HanyiLu WeijuanPan GuiqiongZhou XiaoyuChen YuzhenJin MingyangYang ChangyongDong MingyouLiang Yuexiu - Congenital generalized lipodystrophy (CGL) is a rare disorder marked by near-total loss of adipose tissue and severe metabolic disturbances due to leptin deficiency and the inability to store nutrients in adipose tissue effectively. Metreleptin is the only approved leptin replacement therapy for this condition. Here we present the >20-year follow-up of two sisters with CGL type 1 (AGPAT2 deficiency, OMIM# 608594), enrolled in early metreleptin trials. Clinical outcomes, adherence, immunogenicity, and pregnancies were assessed. Both cases showed rapid and sustained metabolic improvement after metreleptin initiation, allowing insulin discontinuation and triglyceride normalization. Menstrual cycles resumed within six months; allowing both to carry successful pregnancies while continuing metreleptin. Both cases experienced reduced treatment adherence over time, linked to psychological distress. One case developed both anti-drug antibodies and neutralizing activity through immune based assay after 14 years, but without significant clinical impact. In conclusion, these cases highlight both the sustained metabolic benefits of therapy and the complex challenges that may arise over time, such as antibody formation and difficulties in maintaining long-term adherence. Documentation of unmet medical needs can provide guidance and impetus for improved therapeutic approaches to achieve optimum quality of life. - Source: PubMed
Publication date: 2026/05/13
Van der Borght EliseVan der Schueren BartVangoitsenhoven RomanCassiman DavidAkinci BarisBrown Rebecca JOral Elif AMertens AnnMartens Pieter-Jan - The molecular mechanisms regulating the phospholipid (PL) metabolism in the nucleus remain to be elucidated. Here, we describe the role of Dop1a in controlling PL abundance in nuclear membranes (NMs) under the control of mTOR signaling. A shortage of lysophosphatidic acid (LPA) triggers the rapid localization of Dop1a to the nuclear pore complexes (NPCs), where Dop1a suppresses PL synthesis by binding to AGPAT2 (1-acylglycerol-3-phosphate O-acyltransferase 2), which is also localized at the NPCs. Loss of results in elevated PL production, which leads to the formation of nuclear lipid droplets (nLDs). The titration of PL abundance is coordinated with proper cell cycle entry by Dop1a that restricts nuclear accumulation of CDK2. Thus, Dop1a safeguards cell division via surveilling the PL supply. Dop1a is highly expressed in neurons and is essential for neurobehavioral development in mice. mutations have been identified in patients with neurodevelopmental disorders (NDDs). Thus, the proper function of Dop1a is crucial for the proper development of the nervous system. - Source: PubMed
Publication date: 2026/04/22
Ariyama HirotakaTsukamura AtsushiMiyatake SatokoOkado SatokoItabashi ItsukiOgura AmiSuzuki AtsunobuKurakawa HyugaSakaguchi YukiNakatake YuhkiSanada RyunosukeTerakado IchiroKoshimizu ErikoMizuguchi TakeshiHamada KeisukeOgata KazuhiroNakagawa EijiSakakibara TakafumiShirai ManabuFujihara YoshitakaUllah MukhtarQuinodoz MathieuRivolta CarloKhan Abdul GhafoorKhan Muhammad NadeemAnsar MuhammadGerkes Erica HRinne TuulaStegmann Alexander P ASinnema MargjeAlghamdi Malak AliAlharby EssaBalahmar Reham MAlmontashiri Naif A MBaer SarahPiton AmélieCurià Carla DíesMercier SandraCogné BenjaminYap PatrickMorita Shin-YaKakita AkiyoshiKato MitsuhiroMaruo YoshihiroMatsumoto NaomichiMori Masaki - Migrasomes are key organelles in cell-cell communication, playing a role in embryonic morphogenesis, angiogenesis, coagulation, and mitochondrial homeostasis. Migrasome formation involves the assembly of tetraspanin-enriched microdomains (TEMs) into larger macrodomains (TEMAs), but the underlying mechanisms are unclear. Here, we demonstrate that tetraspanin 4 (Tspan4) is highly palmitoylated at six juxtamembrane cysteines. DHHC6 and PPT1 are identified as the main enzymes regulating this modification. Palmitoylation of Tspan4 is critical for Tspan4 clustering and cholesterol recruitment, enabling the TEM to TEMA assembly required for migrasome formation and stabilization. Notably, the palmitoylation-deficient Tspan4 mutant acts in a dominant-negative manner, suppressing migrasome formation not only in cultured cells but also in zebrafish embryos, where it disrupts left-right asymmetry and organ morphogenesis. Collectively, our study establishes protein palmitoylation as a conserved and essential regulator of migrasome assembly, delineating a mechanism whereby Tspan4 palmitoylation drives cholesterol-dependent membrane macrodomain organization to enable migrasome formation and function. - Source: PubMed
Publication date: 2026/04/15
Wang ShuonanWang WeisiQiao JiameiAli SadiqJiang ZhengJiang DongMa JunjieHuang Yuwei