A number of neurodegenerative diseases are associated with defects in the phosphoinositide phosphatase gene FIG4 (MIM:609390), including Charcot-Marie-Tooth disease, type 4J (CMT4J, FBhh0000330), amyotrophic lateral sclerosis 11 (ALS11, FBhh0000335), and Yunis-Varon syndrome (YVS, FBhh0000339); see links in 'Related Diseases'. There is a single fly ortholog, Dmel\FIG4, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human FIG4 gene has not been introduced into flies.
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): E58Y in the fly FIG4 gene (corresponds to D53Y in the human FIG4 gene), implicated in ALS11; I46T in the fly FIG4 gene (corresponds to I41T in the human FIG4 gene), implicated in ALS11 and CMT4J; L22P in the fly FIG4 gene (corresponds to L17P in the human FIG4 gene), implicated in CMT4J.
Pan-neuronal expression of RNAi directed against Dmel\FIG4 results in animals that survive to adult stage, but have significantly shorter life spans and show locomotion defects compared to controls; neuroanatomy defects are observed in third instar larvae. Fat-body-specific knockdown of Dmel\FIG4 results in enlarged lysosomes in fat body cells. Knockdown in the developing eye results in an easily scored rough eye phenotype that facilitates genetic screens for interacting genes; several lncRNAs have been identified in such a screen, including hpRNA:CR18854 and lncRNA:Hsrω. Other genetic interactions of Dmel\FIG4 have also been described; see the FIG4 gene report.
[updated Jan. 2019 by FlyBase; FBrf0222196]
FIG4 Phosphoinositide 5-Phosphatase (FIG4) encodes a protein in the SAC domain-containing protein family; the SAC domain incorporates the phosphoinositide phosphatase activity. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. [from Gene Cards, FIG4; 2016.06.22]
One to one: 1 human to 1 Drosophila.
Ortholog of human FIG4 (1 Drosophila to 1 human). Dmel\FIG4 shares 41% identity and 58% similarity with the human gene.
