Ask about this productRelated genes to: NR0B1 Blocking Peptide
- Gene:
- NR0B1 NIH gene
- Name:
- nuclear receptor subfamily 0 group B member 1
- Previous symbol:
- AHC, DSS
- Synonyms:
- DAX1, AHCH
- Chromosome:
- Xp21.2
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-10-05
Related products to: NR0B1 Blocking Peptide
Related articles to: NR0B1 Blocking Peptide
- Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid progression, early metastasis, frequent relapse, and treatment resistance. Although chemoimmunotherapy has improved outcomes in a subset of patients, reliable molecular stratification tools reflecting tumor heterogeneity and survival risk remain limited. Chaperone-mediated autophagy (CMA) is involved in proteostasis, metabolic adaptation, and stress responses, but its cellular heterogeneity and prognostic relevance in SCLC remain unclear. - Source: PubMed
Publication date: 2026/07/17
Han JiahongXu ShunJiang Yunfeng - Xp21 contiguous gene deletion syndrome is a rare X-linked disorder caused by interstitial deletions involving neighboring genes such as , , , and , and is clinically associated with primary adrenal insufficiency, glycerol kinase deficiency, Duchenne muscular dystrophy, and neurodevelopmental delay. The phenotype depends on deletion size and gene content. We report a male child with a 4.5 Mb hemizygous deletion at Xp21.3-p21.2 encompassing , , , and exons 61 to 79 of , confirmed by exome sequencing and shown to be maternally inherited. The presented patient was admitted at 8 day of life due to concerns for primary muscular or metabolic disease. During the second week of life, the patient developed salt-wasting primary adrenal insufficiency with hyponatremia and hyperkalemia. Persistently elevated creatine kinase exceeding 3000 U/L and markedly elevated cardiac biomarkers were observed in the absence of structural and functional cardiac abnormalities. Urinary organic acid analysis demonstrated significant glyceroluria, and severe serum hypertriglyceridemia was attributed to pseudo-hypertriglyceridemia consistent with glycerol kinase deficiency. Early visual impairment with nystagmus and pale optic discs were noted, and by 15 months the child exhibited global developmental delay, most pronounced in gross motor and language domains. This case illustrates the diagnostic challenges and clinical complexity of Xp21 contiguous gene deletion syndromes. In patients with Xp21 deletion syndrome, early molecular diagnosis enables timely hormone replacement, metabolic surveillance, cardiologic follow-up, and structured neurodevelopmental care. - Source: PubMed
Publication date: 2026/07/20
Frulenko IgnacyOstrowska IwonaPatalan MichałBertoli-Avella AidaLeón Nayla YPinto AndreiaBauer PeterLeśniak AlicjaKatuszonek DariaGlińska MartaModrzejewska MonikaŚmigiel RobertGiżewska Maria - Primary adrenal insufficiency (PAI) is a severe and potentially life-threatening condition characterised by the inability of the adrenal cortex to produce enough glucocorticoids and/or mineralocorticoids. The clinical signs of PAI are primarily due to deficient steroid hormone synthesis and include weight loss, orthostatic hypotension secondary to dehydration, hyponatremia, hyperkalaemia, and hypoglycaemia. In the paediatric population, PAI is most commonly associated with inherited monogenic disorders, particularly enzyme deficiencies. X-linked adrenal hypoplasia congenita (AHC) is a rare condition caused by deletions or single-nucleotide variants in the NR0B1 (DAX1) gene, which encodes the DAX1 protein expressed in the adrenal cortex, gonads, hypothalamus and pituitary gland. Although molecular genetics has significantly expanded our understanding of the aetiology of PAI, clinical diagnosis remains challenging when the initial hormonal findings are atypical, often delaying recognition and treatment. Pathogenic variants of DAX1 can lead to a spectrum of phenotypes, ranging from isolated adrenal insufficiency (AI) to complex syndromic presentations combining AI with hypogonadotropic hypogonadism and impaired spermatogenesis. Here, we report a case of a male patient with AI due to a de novo pathogenic variant in the NR0B1 gene. Furthermore, we provide a non-systematic review of the available literature on the diagnostic challenges facing and clinical variability in AHC, with a particular focus on the paediatric population. This case highlights the importance of a stepwise, comprehensive diagnostic approach to suspected PAI, particularly when initial biochemical and genetic testing is inconclusive. Considering rare causes-such as NR0B1 pathogenic variants in men-can be crucial for establishing a definitive diagnosis, with significant implications for the management of patients and their families. - Source: PubMed
Publication date: 2026/05/31
Montafia IlariaDimarakis SotiriosPartenope CristinaRabbone IvanaBellone SimonettaPetri AntonellaMellone SimonaGiordano MaraProdam Flavia - DAX-1 (NR0B1) is a pivotal regulator of mammalian reproductive and endocrine development. Discovered as a gene whose dosage imbalance can reverse sex in XY individuals, DAX-1 is now recognized as a key component of the network controlling gonadal formation and function. Despite decades of research, the molecular mechanisms of its function in gonad development and function remain only partially understood. We combine genetic, developmental, molecular and biochemical perspectives to present how DAX-1 regulates gene expression from early sex determination and gonadal differentiation to the maintenance of steroidogenic homeostasis in adrenal and gonadal tissues. Recent advances have reshaped our view of DAX-1 beyond its classical role as a transcriptional repressor. Evidence shows that it functions within dynamic transcriptional networks, interacting with regulators such as SF-1 (NR5A1), SOX9 and other nuclear receptors to fine-tune gene expression in a context-dependent manner. Genomic, structural, and proteomic studies reveal that DAX-1 participates in complexes integrating developmental and hormonal cues, coordinating differentiation and steroidogenesis. Moreover, its emerging roles in RNA-associated gene regulation broaden its functions beyond canonical nuclear receptor signaling. We revisit DAX-1 contribution to sex determination and differentiation from an evolutionary and mechanistic viewpoint, emphasizing its interactions with the SRY-SOX9 axis and its dosage-sensitive influence on gonadal fate. The developmental and clinical consequences of DAX-1 mutations and copy number variations manifest as a spectrum of human phenotypes, from adrenal hypoplasia congenita to differences/disorders of sex development (DSD), highlighting its essential role in maintaining endocrine balance. - Source: PubMed
Publication date: 2026/06/20
Bardoni BarbaraLalli Enzo - The regulation of pro-opiomelanocortin (Pomc) expression by the testicular orphan receptor 4 (TR4) constitutes a critical mechanism underlying the pathogenesis of Cushing's disease (CD). Although the endogenous repressor juxtaposed with another zinc finger gene 1 (JAZF1) inhibits TR4 activity, its relatively low binding affinity (K = 2246 nM) limits its therapeutic potential. In this study, we employed an iterative structure-based lead optimization strategy to enhance the JAZF1 scaffold. Utilizing Discovery Studio for virtual screening, we conducted successive rounds of in silico saturation mutagenesis, ranging from single point to multi-site combinatorial substitutions, which were subsequently validated through incremental experimental binding assays. This recursive optimization process led to the identification of two triple-mutant JAZF1 peptides (V56L/A68Y/A69R and D67L/A68Y/A69R) exhibiting more than a 2,200-fold enhancement in TR4 binding affinity. These engineered peptides, along with high-affinity small molecules such as nilotinib (K = 4.83 nM), effectively downregulated Pomc expression and inhibited proliferation of AtT-20 tumor cells. Taken together, these findings suggest that the JAZF1-TR4-Pomc axis may serve as a potential therapeutic target for modulating adrenocorticotropic hormone (ACTH) hypersecretion in CD. - Source: PubMed
Publication date: 2026/06/15
Guoguo WangMeng Su