NFE2L2

Cilia effects upon perturbation of NFE2L2

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Overexpression effect:

Decreased

Ciliogenesis screen results (5 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.54) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Joubert Candidate / Ciliogenesis Defect (robust z=-2.61, ciliated=17.6%) PMID:26595381
• Elliott et al. 2025 (CRISPRa) [CRISPRa]: Disassembly Trigger (casTLE Effect=-4.84) PMID:41160700

Phenotypes

Mouse phenotype:

abnormal skin morphology, increased circulating alkaline phosphatase level, abnormal semil vesicle morphology, abnormal thymus morphology, increased hemoglobin content, enlarged semil vesicle, abnormal lymph node morphology, decreased circulating glucose level, increased mean corpuscular hemoglobin concentration, increased mean platelet volume, abnormal tooth morphology, decreased liver weight, decreased body weight, increased hematocrit, abnormal ovary morphology, enlarged thymus, enlarged lymph nodes, increased erythrocyte cell number, increased mean corpuscular hemoglobin

Human ciliopathy phenotype:

immunodeficiency, developmental delay, and hypohomocysteinemia

Subcellular localization

basal body, centrosome, cilia, cytosol, nucleus, ribosome

References: PMID:41005307, PMID:27020754, PMID:32053600, PMID:31554934

Functional category

• Ciliary assembly/disassembly
• Viral interactions
• Cell migration & adhesion
• Cardiac & muscle development
• Transcription regulation

Function

Also called NRF2. Primary Cilium-Autophagy-Nrf2 (PAN) Axis Activation Commits Human Embryonic Stem Cells to a Neuroectoderm Fate (27020754). Negative regulator of primary ciliogenesis (via p62) and the Hh signaling pathway (through PTCH1), which blocks ciliary traslocation of BBS4 and SMO (32053600). Contradictory paper says that it promotes ciliogenesis (31554934)