Several studies have identified the human gene GIGYF2 (GRB10 Interacting GYF Protein 2) as a possible susceptibility locus for Parkinson disease. Evidence in some studies is consistent with an autosomal dominant mode of inheritance, with variable penetrance, but these results are not observed in other similar studies (see MIM:607688). The GIGYF2 protein is thought to act cooperatively with GRB10 in the regulation of tyrosine kinase receptor signaling; it is a component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation. There is a single orthologous gene in Drosophila, Gyf, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\Gyf is orthologous to a second similar gene in human, GIGYF1.
The human GIGYF2 gene has not been introduced into flies.
Animals homozygous for an amorphic mutation of Dmel\Gyf exhibit defects in developmental or starvation-induced accumulation of autophagosomes and autolysosomes in the larval fat body. In adults, increased accumulations of ubiquitinated proteins and dysfunctional mitochondria in neuron and muscle are observed, leading to locomotor defects and reduced lifespan. Physical interactions of Dmel\Gyf have been described; see below and in the Gyf gene report.
Since dysregulation of autophagy and mitochondrial dysfunction are observed in other forms of Parkinson disease, these results lend support to the hypothesis that GIGYF2 is a susceptibility locus for the disease.
[updated Sep.2017 by FlyBase; FBrf0222196]
Parkinson disease (PD) is a neurodegenerative disease usually typified by slow onset in mid to late adulthood; there are also early-onset and juvenile forms of the disease. Symptoms worsen over time and include resting tremor, muscular rigidity, bradykinesia [abnormal slowness of movement], and postural instability [impaired balance and coordination]; additional symptoms may include postural abnormalities, dysautonomia [symptoms caused by malfunction of the autonomic nervous system], dystonic cramps, and dementia. Parkinson disease is the second-most common neurodegenerative disease (after Alzheimer disease), affecting approximately 1% of the population over 50 (Polymeropoulos et al., 1996, pubmed:8895469). [from MIM:168600; 2013.07.23]
Parkinson disease is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 may be referred to as juvenile-onset disease. [from Genetics Home Reference, GHR_condition:parkinson-disease, 2015.02.13]
[PARKINSON DISEASE 11, AUTOSOMAL DOMINANT, SUSCEPTIBILITY TO; PARK11](https://omim.org/entry/607688)
[GRB10-INTERACTING GYF PROTEIN 2; GIGYF2](https://omim.org/entry/612003)
There is conflicting evidence that susceptibility to Parkinson disease is conferred by heterozygous mutation in the GIGYF2 gene. [from MIM:607688; 2017.09.29]
GIGYF2 encodes a protein that is a component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation. The encoded protein may act cooperatively with GRB10 in the regulation of tyrosine kinase receptor signaling. [Gene Cards, GIGYF2; 2017.09.29]
Many to one (2 human to 1 Drosophila); the human genes are GIGYF2 and GIGYF1.
Moderate-scoring ortholog of human GIGYF2 and GIGYF1 (1 Drosophila to 2 human); Dmel\Gyf shares 21-23% identity and 32-36% similarity with the human genes.
