Alternative titles; symbols
HGNC Approved Gene Symbol: FAIM2
Cytogenetic location: 12q13.12 Genomic coordinates (GRCh38) : 12:49,866,896-49,903,900 (from NCBI)
Apoptosis, or programmed cell death, is used in a number of biologic processes from modeling the embryo and regulating the immune system to tumor regression. Conversely, dysfunction of this system has been implicated in oncogenesis, development of autoimmunity, and degenerative diseases. Intense study of this process identified membrane-bound receptors and their cognate ligands that together begin the program that ultimately leads to cell death. The FAS receptor, also called CD95 or Apo1, is one such receptor, of which the gene is designated TNFRSF6 (134637) to indicate that it is a member of the tumor necrosis factor (TNF) receptor superfamily. The apoptotic signal must itself be tightly controlled to avoid inappropriate cell death. Somia et al. (1999) established a genetic screen to search for molecules that inhibit the apoptotic signal from the FAS receptor. They isolated a gene, called LFG ('lifeguard'), and found that it is the human homolog of a rat protein, neuromembrane protein-35 (NMP35), described by Schweitzer et al. (1998). The LFG open reading frame encodes a 316-amino acid protein predicted by hydropathy plots to contain 7 membrane-spanning domains. They found that LFG protects cells uniquely from FAS but not from the mechanistically related tumor necrosis factor-alpha (191160) death signal. LFG is widely distributed, but remarkably is highly expressed in the hippocampus. LFG can bind to the FAS receptor, but does not regulate FAS expression or interfere with binding of an agonist antibody. Furthermore, LFG does not inhibit binding of FADD (602457) to FAS.
Somia et al. (1999) used a human/rodent somatic hybrid panel to map the LFG gene to chromosome 12. This localization was confirmed by fluorescence in situ hybridization, with a subchromosomal location of 12q13.
Schweitzer, B., Taylor, V., Welcher, A. A., McClelland, M., Suter, U. Neural membrane protein 35 (NMP35): a novel member of a gene family which is highly expressed in the adult nervous system. Molec. Cell. Neurosci. 11: 260-273, 1998. [PubMed: 9698393] [Full Text: https://doi.org/10.1006/mcne.1998.0697]
Somia, N. V., Schmitt, M. J., Vetter, D. E., Van Antwerp, D., Heinemann, S. F., Verma, I. M. LFG: an anti-apoptotic gene that provides protection from Fas-mediated cell death. Proc. Nat. Acad. Sci. 96: 12667-12672, 1999. [PubMed: 10535980] [Full Text: https://doi.org/10.1073/pnas.96.22.12667]