FEM1C encodes a substrate receptor subunit of a cullin-RING E3 ubiquitin ligase complex. This gene is part of the ubiquitin-proteasome system—a critical cellular pathway through which the cell disposes of unneeded or damaged proteins. Under normal circumstances, FEM1C identifies certain proteins that carry a short signal at their very end (often involving arginine) and labels them for orderly clearance.
Specific changes in FEM1C (notably Asp126His and Asp126Val) disrupt the portion of the protein that recognizes these signals. As a result, substrates may accumulate instead of being broken down, which can contribute to neurological issues. Clinical observations so far associate the aforementioned variants with severe developmental delay, absent speech, pyramidal signs (such as increased muscle tone and brisk reflexes), and limb ataxia, underlining the critical role played by this particular site in FEM1C.
Thus far, only a few individuals with a FEM1C variant have been reported. The inheritance pattern appears de novo in these cases, but the full inheritance spectrum is not definitively established. Prevalence of FEM1C-related disorders is unknown.
FEM1C