LFNG

The LFNG gene provides the instructions for a protein that helps control (regulate) the Notch pathway, an important pathway in embryonic development. The Notch pathway plays a critical role in the development of vertebrae. Specifically, the LFNG protein and the Notch pathway are involved in separating future vertebrae from one another during early development, a complex process called somite segmentation. Although the exact mechanism of somite segmentation is unclear, it appears to require the activity of several proteins in the Notch pathway, including the NOTCH1 protein and the LFNG protein, to be turned on and off in a specific pattern (oscillate).

The LFNG protein regulates the activity of the NOTCH1 protein. Using a mechanism called glycosylation in which a group of sugar molecules is attached to a protein, the LFNG protein modifies the NOTCH1 protein as it is being processed. This modification has multiple effects: it alters Notch signaling in response to other proteins called ligands that attach (bind) to the NOTCH1 protein, and it blocks (represses) the activation of the NOTCH1 protein in some regions of the cell.

spondylocostal dysostosis - caused by mutations in the LFNG gene

At least one mutation in the LFNG gene causes a rare type of spondylocostal dysostosis, called spondylocostal dysostosis type 3, which is a condition characterized by abnormal development of bones in the spine and ribs. The identified mutation replaces the protein building block (amino acid) phenylalanine with the amino acid leucine at position 188 (written as Phe188Leu or F188L). The mutated LFNG protein cannot modify the NOTCH1 protein. Consequently, the NOTCH1 protein is constantly active and does not oscillate, so somite segmentation does not occur properly. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylocostal dysostosis type 3.