NRF2 Stress Response

Gene co-expression module in Natural Killer cells

View this module in SCUBA

Why this annotation

This module contains a diverse set of genes with uniform expression across NK cell subsets. Hub genes include FAM133B (poorly characterized), JOSD1 (deubiquitinase), UBE2B (ubiquitin-conjugating enzyme E2B), KMT2E (histone methyltransferase), CWC25 (spliceosome component), NFE2L2 (NRF2, master oxidative stress transcription factor), PRMT9 (arginine methyltransferase), RUNX3 (transcription factor critical for NK/T cell differentiation and gut residency), DDX18 (RNA helicase), and CNOT6L (CCR4-NOT deadenylase). The module is significantly upregulated in CD inflammation. NFE2L2/NRF2 is a canonical oxidative/electrophilic stress response regulator; UBE2B and JOSD1 are ubiquitin pathway components often co-regulated under stress. KMT2E and PRMT9 are chromatin/epigenetic regulators. RUNX3 is notable for gut NK cell residency and activation. The combination of NRF2-driven stress response with ubiquitin/proteasome pathway genes and epigenetic regulators suggests a stress-activated transcriptional response. The CD-specific upregulation supports an inflammatory stress context. Neighbor modules also show CD-specific upregulation, supporting a shared inflammatory activation neighborhood.

Genes

C1orf56, CNOT6L, CWC25, DDX18, FAM133B, JOSD1, KMT2E, NFE2L2, PRMT9, RUNX3, UBE2B

Most correlated modules

• NK Activation Response · correlation 0.89
• Cytokine Feedback Response · correlation 0.88
• NK Cell Activation · correlation 0.86
• TGF-beta Repression · correlation 0.86
• NF-κB Activation · correlation 0.86
• Metabolic Activation · correlation 0.86
• mRNA Splicing · correlation 0.86
• MAPK/AP-1 Signaling · correlation 0.85

Module annotations were drafted by a large language model from the module's genes, then reviewed and approved by a domain expert. See sources & licences.