Set-binding factor 1 (SBF1) (SBF1)

Set-binding factor 1 (SBF1), also known as Myotubularin-related protein 5 (MTMR5), is a member of the myotubularin family of phosphoinositide phosphatases (UniProt O95248). Although it lacks catalytic activity due to mutations in its phosphatase domain, it acts as a critical pseudophosphatase and adapter protein that regulates the activity and localization of the active phosphatase MTMR2 (PubMed: 12668758). SBF1 also functions as a guanine nucleotide exchange factor (GEF) for Rab proteins, such as RAB28, and plays a significant role in membrane trafficking, autophagy, and axonal myelination (PubMed: 20937701, 35580604). Loss-of-function mutations in the SBF1 gene are the primary cause of Charcot-Marie-Tooth disease type 4B3 (CMT4B3), a severe demyelinating peripheral neuropathy characterized by focally folded myelin sheaths and progressive muscle atrophy (Neurology: 10.1212/WNL.0b013e31829a33d6). Additionally, SBF1 deficiency has been linked to male infertility, specifically nonobstructive azoospermia, and potential neurocognitive impairments (GeneCards). While there are currently no approved drugs directly targeting SBF1, therapeutic research focuses on gene replacement strategies and the modulation of downstream phosphoinositide signaling and autophagic pathways to mitigate the effects of its deficiency.

Other names

Myotubularin-related protein 5MTMR5CMT4B3DENND7AInactive phosphatidylinositol 3-phosphatase 5DENN/MADD domain-containing 7ASET-binding factor 1

None currently approved; therapeutic strategies focus on gene replacement therapy or modulation of the MTMR2-SBF1 regulatory axis and downstream autophagy pathways.