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FB2026_01
,
released March 12, 2026
The human gene SREBF1 (sterol regulatory element binding transcription factor 1) has been identified in a genome-wide association study (GWAS) as a possible susceptibility locus for Parkinson disease. SREBF1, and the related gene SREBF2, are (bHLH-Zip) transcription factors that control cholesterol and lipid homeostasis by stimulating transcription of sterol-regulated genes. There is a single orthologous gene in Drosophila, SREBP, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Neither of the human genes, SREBF1 nor SREBF2, has been introduced into flies. These genes are also referred to as SREBP1 and SREBP2.
SREBP was identified in a genome-wide RNAi screen in Drosophila S2R+ cells to identify genes that promote or inhibit park translocation and mitophagy following mitochondrial depolarization (FBrf0226429). Provision of exogenous lipids ameliorates the effect, thus suggesting a role for lipid metabolism in the regulation of mitophagy following loss of membrane potential.
Homozygous loss-of-function mutations of Dmel\SREBP are lethal, usually during the larval stages. Systemic loss of function effected by RNAi results in a dose-dependent developmental delay and lethality during larval and pupal stages. Surviving adults show a significant reduction in body size, body weight and wing area. Physical and genetic interactions of SREBP have been described; see below and in the SREBP gene report.
[updated Apr. 2021 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]
A GWAS analysis has associated a variant of the SREBF1 locus with onset of sporadic Parkinson disease (see GWAS Catalog, below in 'External links').
SREBF1 encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1); the protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. [Gene Cards, SREBF1; 2017.05.02]
Sterol regulatory element-binding protein-1 (SREBP1) and SREBP2 are structurally related proteins that control cholesterol homeostasis by stimulating transcription of sterol-regulated genes (summary by Osborne, 2001; pubmed:1485982). [from MIM:184756; 2017.05.02]
Many to one: 2 human to 1 Drosophila; second human gene is SREBF2.
High-scoring ortholog of human SREBF1 and SREBF2 (1 Drosophila to 2 human); Dmel\SREBP shares 31-32% identity and 44-47% similarity with the human genes.