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General Information
Name
Parkinson disease, susceptibility to, SREBF1-related
FlyBase ID
FBhh0000532
Disease Ontology Term
Parent Disease
OMIM
Overview

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. SREBP1, and the related gene SREBP2, 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 SREBP2, has been introduced into flies.

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. Genetic interactions of SREBP have been described; see the SREBP gene report.

[updated May 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Parkinson disease
Symptoms and phenotype

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 OMIM: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]

Specific Disease Summary: Parkinson disease, susceptibility to, SREBF1-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

A GWAS analysis has associated a variant of the SREBF1 locus with onset of sporadic Parkinson disease (see GWAS Catalog, below in 'External links').

Cellular phenotype and pathology
Molecular information

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 OMIM:184756; 2017.05.02]

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]

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; second human gene is SREBF2.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Sterol regulatory element binding protein (SREBP) encodes a membrane protein that functions as a master-regulator of lipogenesis. It activates transcription of lipogenic genes upon reduction of lipid or cholesterol levels. [Date last reviewed: 2019-02-28]
      Gene Groups / Pathways
      Comments on ortholog(s)

      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.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (1 groups)
      protein-protein
      Interacting group
      Assay
      References
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 2 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      piggyBac activity
      References (8)