Ask about this productRelated genes to: HYOU1 antibody
- Gene:
- HYOU1 NIH gene
- Name:
- hypoxia up-regulated 1
- Previous symbol:
- -
- Synonyms:
- ORP150, HSP12A, Grp170
- Chromosome:
- 11q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-05-27
- Date modifiied:
- 2017-05-09
Related products to: HYOU1 antibody
Related articles to: HYOU1 antibody
- Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis. - Source: PubMed
Publication date: 2026/09/07
Idani AidaBibi-Triki SabrinaStemmelen TristanRadosavljevic MirjanaGrenot PierreHirschler AurélieBernard AliceRosenzwajg MichelleYang JianyingEischen AliceNaegely LydieMacquin CécilePichot AngéliqueSpinnhirny PerrineHanauer AntoineAlipour-Olayei NasrinCherrier ThomasKolmer AlinePaul NicodèmeOlson Rory JMorava EvaMiao ZhichaoCarapito ChristineRostami ParastooParvaneh NimaShahrooei MohammadMolitor AnneCarapito RaphaelBahram Seiamak - Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis. - Source: PubMed
Publication date: 2026/09/07
Idani AidaBibi-Triki SabrinaStemmelen TristanRadosavljevic MirjanaGrenot PierreHirschler AurélieBernard AliceRosenzwajg MichelleYang JianyingEischen AliceNaegely LydieMacquin CécilePichot AngéliqueSpinnhirny PerrineHanauer AntoineAlipour-Olayei NasrinCherrier ThomasKolmer AlinePaul NicodèmeOlson Rory JMorava EvaMiao ZhichaoCarapito ChristineRostami ParastooParvaneh NimaShahrooei MohammadMolitor AnneCarapito RaphaelBahram Seiamak - : Ankylosing Spondylitis (AS) and inflammatory bowel disease (IBD) exhibit substantial pathophysiological overlap, including dysregulated innate immunity, barrier dysfunction, and Th17-mediated inflammation. However, whether Na overload-related genes (NRGs) exhibit shared transcriptional alterations in IBD and AS remains unclear. This study aimed to characterize the expression patterns of NRGs across IBD and AS and to identify candidate genes associated with both diseases. : Differential expression analysis was performed to identify differentially expressed NRGs (DE-NRGs) in diseased tissues relative to normal tissues. Shared DE-NRGs between IBD and AS were screened and defined as common differentially expressed NRGs (Co-DE-NRGs). We then analyzed the correlations of these Co-DE-NRGs and explored their relationships with immune cell infiltration in target tissues. Four machine learning algorithms were applied to screen key NRGs associated with both IBD and AS. Potential therapeutic agents targeting these core biomarkers were predicted using drug-gene interaction databases, and molecular docking was conducted for further validation. : A total of 32 shared Co-DE-NRGs were identified for IBD and AS, with nine key regulatory NRGs recognized: , , , , , , , , and . Exploratory MR analysis identified disease-specific associations between genetically predicted expression of NRGs and CD, UC, and AS. Genetically predicted expression showed positive associations with CD and UC but an inverse association with AS and therefore did not represent a consistent risk factor across the three diseases. Furthermore, transcriptome-based drug-response analysis identified four candidate agents shared between AS and at least one IBD dataset: ciclosporin, BCL-LZH-4, BRD-K79669418, and CID-5951923. Exploratory molecular docking generated STAT3 binding poses for BCL-LZH-4 and CID-5951923, with DOCK Grid Scores of -35.321896 and -28.361128, respectively. CID-5951923 was selected for representative visualization of its predicted interaction with STAT3. Single-cell RNA-sequencing analysis identified tissue- and cell-type-specific mRNA expression patterns in the analyzed IBD colonic and AS peripheral-blood datasets, with monocytes representing a major cell population exhibiting detected expression in the AS dataset. : These findings identify shared NRG-related transcriptional alterations in IBD and AS, with emerging as a candidate gene associated with both diseases. Further experimental studies are required to determine whether these alterations reflect the involvement of NECSO and to evaluate their potential diagnostic or therapeutic relevance. - Source: PubMed
Publication date: 2026/08/11
Wu LuojinOu ChenghaoLiu XuanYan MiaohanGuan JinghanWang XinfengMao LimingXu QiuyunLiu Zhaoxiu - A strong crosstalk exists between endoplasmic reticulum (ER) stress and synovitis. Beyond their canonical role in protein folding, ER stress chaperones may promote inflammation, cell survival, and fibroblast activation under pathological conditions. This study aimed at localizing and quantifying 11 ER stress proteins (BiP, HYOU1, MANF, PDIA4, GANAB, HSP90B1, TXNDC5, DNAJB11, LMAN1, ERP29, CALR) in human inflamed synovial membranes and at investigating their expression in fibroblast-like synoviocytes (FLS) under ER stress, pro-inflammatory, or pro-fibrotic stimuli. By immunohistochemistry, on a first cohort of formalin-fixed paraffin-embedded (FFPE) biopsies obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPPA), and rheumatoid arthritis (RA), these ER chaperones were primarily localized to the lining in low-grade inflammation (Tak <4) and expanded to the sublining under high inflammatory conditions (Tak ≥4), with a widespread distribution in RA. Imaging mass cytometry, applied to a second cohort of FFPE tissue samples collected from patients diagnosed with OA and RA, revealed the co-expression of ER stress proteins with CD55⁺ FLS in the lining and their progressive infiltration into the sublining along with CD34⁺CD31 FLS during inflammation. These observations were confirmed by immunofluorescence on a larger cohort of OA patients. As inflammation progresses, there is a loss of co-expression with CD55 in the lining, accompanied by a gradual shift towards co-expression with CD34 in the sublining. In vitro, ER stress proteins, particularly BiP, HYOU1, MANF, PDIA4, HSP90B1, LMAN1, CALR, and DNAJB11 are overexpressed in human OA FLS following ER stress, pro-inflammatory or pro-fibrotic stimulation, with BiP, PDIA4, HSP90B1, ERP29, and CALR also being secreted. PDIA4 emerged as a central player: its depletion significantly impaired FLS proliferation and migration, highlighting a direct role in driving synovitis. This study provides the first spatial and functional characterization of ER chaperones in human arthritic synovium, linking ER stress to fibroblast plasticity, inflammation, and fibrosis. - Source: PubMed
Publication date: 2026/08/12
Gendebien ZoéPoulet ChristopheDeroyer CélinePaulissen GenevièveSalpetier PaulineHego AlexandreLefèvre GaëtanCobraiville GaëlNeuville SophiePlener ZeldaDaniel ChristopheThirion ThierrySokolova TatianaDurez PatrickHemon PatriceDelarue YunaMarec NadègeBianchi ElettraDelvenne PhilippeRibbens Cliode Seny Dominique - The independent evolution of hypoxia tolerance across phylogenetically distinct species, including marine mammals, highland species, and subterranean mammals, represents a classic example of convergent evolution. Although these taxa produced similar physiological solutions to address comparable evolutionary challenges, the underlying genetic mechanisms of their convergent adaptation remain poorly understood. Here, we investigated genomic signatures of convergent evolution in hypoxia-tolerant mammals. Hypoxia-tolerant lineages exhibited accelerated rates of protein evolution relative to normoxia-adapted species. We identified 499 positively selected genes and 1585 rapidly evolving genes in hypoxia-tolerant mammals, with significant functional enrichment related to hypoxia response and cardiovascular regulation. We also detected 817 genes showing convergent shifts in relative evolutionary rates at the protein-coding level across hypoxia-tolerant species. Widespread lineage-specific amino acid substitutions were detected, a subset of which occur within key functional domains implicated in hypoxia adaptation. Remarkably, functional assays demonstrated that overexpression of cetacean HYOU1 (hypoxia up-regulated protein 1) significantly reduced malondialdehyde and reactive oxygen species levels, while suppressing hypoxia-induced target gene expression, compared with human ortholog and mutation constructs. Together, these findings provide genomic and functional evidence for convergent genetic mechanisms underlying hypoxia adaptation in mammals. - Source: PubMed
Publication date: 2026/08/04
Dong HaoWang ChunxuPei EnqingZhao LiangChai SiminTian Ran