Ask about this productRelated genes to: PSMB9 antibody
- Gene:
- PSMB9 NIH gene
- Name:
- proteasome subunit beta 9
- Previous symbol:
- LMP2
- Synonyms:
- RING12, beta1i, PSMB6i
- Chromosome:
- 6p21.32
- Locus Type:
- gene with protein product
- Date approved:
- 1991-12-18
- Date modifiied:
- 2016-10-05
Related products to: PSMB9 antibody
Related articles to: PSMB9 antibody
- Complex human diseases exhibit substantial clinical heterogeneity driven by poorly understood molecular mechanisms, while many also lack sufficient molecular and omics data for mechanistic investigation, hindering therapeutic development. We introduce PiMInfer, a phenotype-to-mechanism framework that leveraged largely available real-world clinical data-based deep phenotypic characterizations with a biomedical knowledge graph approach to resolve disease clinical heterogeneity into phenotype-informed molecular modules, thereby accelerating therapeutic target discovery. We applied PiMInfer to investigate Hidradenitis Suppurativa (HS), an autoimmune skin disease with poorly understood pathogenesis and limited treatment options. PiMInfer identified a coherent, phenotype-informed HS gene module (PiHSM) and functional endotypes, which were validated using multimodal evidence. In silico drug repurposing using PiHSM prioritized Carfilzomib, targeting the immunoproteasome subunit PSMB9, essential for MHC Class I antigen presentation. Preclinical testing using human patient lesional skin explants confirmed its anti-inflammatory activity and demonstrated a significant downregulation of IFN-γ, IL-17, and mTOR signaling pathways within HS lesional microenvironment through single-cell RNA sequencing. PiHSM-based network predictions further suggest a potential enhanced efficacy of combining Carfilzomib with approved HS agents. Collectively, PiMInfer provides a scalable framework that bridges real-world phenome-wide comorbid associations to mechanism-anchored therapeutic discovery, enabling a paradigm shift in precision medicine approaches for complex diseases with limited molecular characterization and in need of better therapeutic strategies. - Source: PubMed
Publication date: 2026/05/17
Wang Wei-TingZhou ManqiTong JieLin Meng-JuKe AlisonWei MeihanXu ZhenxingTai HansenParvathaneni AarthiHill Khyla TCohen Steven RPetukhova LynnChiu Ernest SWang FeiLu Catherine PSu Chang - Preterm birth (PTB, < 37 weeks of gestation) is a major public health concern in the United States, with Black women experiencing a higher incidence compared to White women. Although some studies have identified social, medical, and obstetric risk factors for PTB, the biological mechanisms underlying spontaneous PTB (sPTB) risk remain unclear. We conducted a secondary analysis using data from Black participants enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), (n = 1073) from 2010 to 2013. Peripheral whole blood samples were collected from all participants between 6 + 0/7 and 13 + 6/7 weeks of gestation. Demographic, behavioral and clinical data were gathered through surveys, and pregnancy outcomes were obtained through chart abstraction. We used the Infinium Methylation EPIC v2.0 BeadChip for epigenome-wide association (EWAS) of DNA methylation and sPTB. - Source: PubMed
Publication date: 2026/05/24
Zhao TingtingZhao YihongReho PaoloSamari GoleenWapner RonaldHazi ArielleWu HaotianBarcelona Veronica - Despite significant advances, the molecular basis and thus patient-tailored therapeutic options for inborn errors of immunity remain unknown in a significant number of patients. - Source: PubMed
Publication date: 2025/11/18
Fournier BenjaminPoirier LéaAbramowski VincentMerlin EtienneDeutsch HélèneBastard PaulCallebaut IsabellePicard CapucineRosain JérémieKüry SébastienBézieau StéphaneFabre MoniqueCastelle MartinNeven BénédicteMoshous Despinade Villartay Jean-PierreEbstein Frédéric - Monoallelic variants in catalytic immunoproteasome subunits have recently been linked to proteasome-associated autoinflammatory syndromes with immunodeficiency (PRAAS-ID), yet their molecular mechanisms and clinical spectra are not fully defined. In this study, seven individuals from five unrelated families carrying five distinct monoallelic PSMB8 variants were identified. Individuals presented with neonatal-onset immunodeficiency characterized by recurrent infections, B cell lymphopenia, and hypogammaglobulinemia requiring immunoglobulin replacement. Inflammatory manifestations of variable severity included enteropathy, hepatitis, myositis, and inflammatory lung disease. Additional findings included leukocyte vacuolization in blood and bone marrow. Pathogenic variants in immunoproteasome subunits were analyzed to identify structural features associated with dominant-negative behavior. Immunoproteasome assembly and activity were investigated using complexome profiling, immunoblotting, and in-gel activity assays in proband-derived fibroblasts and transfected HEK293T cells, with downstream effects assessed by proteomic and RT-qPCR analyses. Mutant PSMB8 subunits were inefficiently incorporated into immunoproteasome complexes, leading to impaired assembly, including reduced fully assembled complexes and accumulation of assembly intermediates. This defect was accompanied by activation of the integrated stress response alongside impaired immune signaling. Monoallelic pathogenic variants in PSMB8, PSMB9, and PSMB10 associated with PRAAS-ID affected residues that are highly conserved and biophysically similar between the three immunoproteasome catalytic subunits. These shared structural features may help identify additional variants with similar disruptive effects on immunoproteasome assembly. Together, our data show that monoallelic PSMB8 variants disrupt immunoproteasome assembly, resulting in clinically variable disease with immunodeficiency and systemic inflammation. Our findings support immunoproteasome assembly disruption as a unifying dominant-negative mechanism underlying PRAAS-ID. - Source: PubMed
Publication date: 2026/05/21
Wijngaard Robinvan der Made Caspar IKalkan Uçar SemaRamakrishnan GayatriWang ManBrand JohannesRosenfeld Jill AVogel Tiphanie PNicholas Sarah KWeisz-Hubshman Monika van Karnebeek Clara D MAllenspach Eric JGardiner Taylor EPerera Kimmantudawage SumuduStark ZornitzaArmstrong Ruth KCampbell JanineVolpi StefanoDrago EnricoGattorno MarcoGrossi AliceCeccherini IsabellaCabrera-Orefice AlfredoSiebels BenteMair ThomasSchlüter HartmutSmeets Ruben Lvan Beek RonaldGoebel IngridKüchler KatrinGersting Søren WHoischen AlexanderVissers Lisenka E L MWevers Ron AMeyer-Schwesinger CatherineWortmann Saskia BOud Machteld MGuerrero-Castillo Sergio - Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by progressive joint destruction and functional impairment. Increasing data indicate that glutamate metabolism is critically involved in RA pathogenesis. This analysis aimed to identify glutamate metabolism-related biomarkers and potential RA therapeutics. - Source: PubMed
Publication date: 2026/04/29
Zhu BingruiLi BaoliangZhang ShuxuQi WenzhuoMu ZhouKong PengHan YingguangShi Zhigang