NDUFAF2

Cilia effects upon perturbation of NDUFAF2

Cilia number / % ciliated:

Decrease

Loss-of-function effect:

Decrease

Ciliogenesis screen results (4 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (z=3.50) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, neg_rank=235, lfc=-2.57) PMID:30270045
• Elliott et al. 2025 (CRISPRa) [CRISPRa]: Disassembly Trigger (casTLE Effect=-5.39) PMID:41160700

Phenotypes

Mouse phenotype:

Loss causes ciliary defects alongside mitochondrial dysfunction.

Subcellular localization

cilia associated gene, mitochondria

Functional category

• Ciliary assembly/disassembly

Function

We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9 (38949024). NDUFAF2 (Leigh syndrome gene) is necessary and sufficient for cilia formation. Loss causes both mitochondrial and ciliary defects in vitro and zebrafish. Binds ARMC9 (Joubert gene); NAD+ supplementation rescues ciliary dysfunction in ARMC9-deficient cells and zebrafish, and ameliorates ocular/motor deficits in ARMC9-deficient patient (PMID:38949024).

Model organism evidence