Ask about this productRelated genes to: IFNGR2 antibody
- Gene:
- IFNGR2 NIH gene
- Name:
- interferon gamma receptor 2
- Previous symbol:
- IFNGT1
- Synonyms:
- AF-1
- Chromosome:
- 21q22.11
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2019-04-23
Related products to: IFNGR2 antibody
Related articles to: IFNGR2 antibody
- Immune checkpoint blockade (ICB) is a standard treatment for several types of human cancer, yet we still lack a deep understanding of the mechanisms underlying primary resistance. Tumor-intrinsic defects in immune recognition and interferon-gamma (IFNγ) signaling pathways facilitate immune evasion and may limit the efficacy of ICB. Here, we delineate the mutational landscape and functional consequences of amino acid substitutions in key immune-related genes, B2M, CALR, IFNGR1, IFNGR2, JAK1, and JAK2, across more than 12,000 primary tumors and cancer cell lines. Genomic alterations affecting the coding regions of at least one of these genes were identified in approximately 11% of cancers, with missense variants accounting for 55% of these events. B2M, encoding the invariant light chain of the heavy chain-I (HLA-I) complex, exhibited the highest mutation frequency per base pair, the mutations predominantly involving truncating variants. A curated set of 2156 missense mutations in B2M and in components of the IFNγ-signaling pathway (IFNGR1, IFNGR2, and JAK2) was analyzed using SIFT, PolyPhen-2, and AlphaMissense, yielding predicted pathogenicity rates of 52%, 35%, and 27%, respectively. The functional assays, performed in lung cancer cells, revealed JAK2 and IFNGR1 variants that impaired IFNγ-mediated transcriptional activation and growth suppression, and B2M variants that disrupted HLA class I complex formation. Notably, AlphaMissense predictions showed the highest concordance with experimental data. These findings provide a detailed mutational map of antigen presentation and IFNγ-response components in cancer. Overall, our results provide a resource of specific mutations in genes involved in immune pathways that compromise tumor immunogenicity and will serve for support in patient selection for response to ICB. - Source: PubMed
Publication date: 2026/04/04
Diaz Cristina AMorillas Juan MNavajas-Chocarro PabloProvenzano ValentinaSetien FernandoEsteller ManelSanchez-Cespedes Montse - Tumor necrosis factor (TNF) orchestrates immune responses but can also drive inflammation-associated tissue damage. However, the mechanisms governing tissue tolerance to TNF remain poorly understood. Here, we reveal that TNF receptor 1 (TNFR1) abundance is regulated by two upstream open reading frames (uORFs) in the 5' untranslated region of and demonstrate that this is a key determinant of TNF tolerance. uORF2 dominantly limits TNFR1 translation, and its disruption increases TNFR1 levels, leading to excessive TNF-induced gene activation and cell death in cell culture. By contrast, uORF1 dynamically regulates TNFR1 levels in response to inflammatory and stress signals. In mice, uORF2 protects against TNF-driven systemic inflammatory response syndrome and liver pathology. We additionally report that the translation of other immune receptor messenger RNAs, including , , and , is also controlled by uORFs. Thus, regulation of TNFR1 levels and possibly of other immune receptors emerges as a mechanism safeguarding against excessive immune responses and tissue damage. - Source: PubMed
Publication date: 2026/04/03
Ma BiaoLyu WenxinRizk JohnHan XiaoyueKjær MajkenPereira Almeida VinnyciusJessen MalinSauerland Max BenjaminLeung Carol Sze KiVan den Eynde Benoit JLu XinGyrd-Hansen Mads - Dilated cardiomyopathy (DCM) is a prevalent myocardial disease with a grim poor prognosis, and its pathogenesis remains poorly understood. Necroptosis, a programmed cell death mechanism, is believed to be significantly involved in the pathogenesis of DCM. This study aimed to identify necroptosis-related hub genes associated with DCM and predict potential agents for DCM. All analyses exclusively utilized publicly available datasets from the Gene Expression Omnibus database. Differentially expressed genes were identified in the DCM dataset GSE128095. The least absolute shrinkage and selection operator and random forest algorithms were then employed to identify 5 necroptosis-related hub genes. A diagnostic model for DCM was constructed based on these hub genes, and the expression profiles of these genes across different myocardial cell populations were systematically analyzed using single-cell RNA sequencing data from GSE184899 dataset. Furthermore, the drug-gene interaction database was utilized to identify potential therapeutic candidates targeting these hub genes. A total of 17 necroptosis-related genes were identified, primarily associated with biological processes such as apoptosis, antiviral immune response, and autophagy, with a particular localization in lysosome/autophagy-related structures and membrane functional regions. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that these genes predominantly regulated the necroptosis and NOD-like receptor signaling pathways. Five necroptosis-related hub differentially expressed genes (CAPN1, SLC25A5, IFNGR2, CAMK2A, and BIRC3) were pinpointed. The DCM diagnostic model based on these 5 hub genes demonstrated excellent diagnostic efficacy. These hub genes displayed distinct expression profiles across various cardiac cell types. Notably, the upregulated hub genes in DCM including SLC25A5, IFNGR2, and CANP1, exhibited increased expression in multiple cardiac cell types, encompassing cardiomyocytes, smooth muscle cells, and endothelial cells. Conversely, the downregulated gene CAMK2A in DCM displayed a specific expression preference in fibroblasts. Finally, Calpeptin was predicted as a potential therapeutic agent for DCM. This study computationally identified 5 hub genes associated with necroptosis in DCM, developed a diagnostic model, and proposed one potential therapeutic drug, providing novel insights for the diagnosis and management of DCM. - Source: PubMed
Xia MengJi YananZhu Hongtao - Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease, triggered by a complex interplay between genetic, environmental and epigenetic factors. We investigated the methylation profile of peripheral CD4(+) lymphocytes from PBC patients compared to healthy controls (HC) and autoimmune hepatitis (AIH) patients, to elucidate gene specific epigenetic modifications that contribute to PBC pathogenesis, as similar data are limited. - Source: PubMed
Publication date: 2025/09/09
Arvaniti PinelopiZachou KalliopiLyberopoulou AggelikiSevdali EiriniGabeta StellaSpeletas MatthaiosRenaudineau YvesDalekos George N - Colorectal cancer (CRC) is a significant global health burden, ranking amongst the top causes of cancer-associated mortality. Emerging evidences implicate gut microbiota as a prominent mediator of cell signalling, immune, and metabolic pathways in the pathophysiology of CRC. - Source: PubMed
Publication date: 2025/10/21
Haque ShafiulBantun FarkadJalal Naif AFaidah HaniBabalghith Ahmad OAlobaidy Mohammad AhmadAldairi Abdullah FAhmad Faraz