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General Information
spastic paraplegia 17
FlyBase ID
Disease Ontology Term
Parent Disease

This report describes spastic paraplegia 17 (SPG17), which is an autosomal dominant subtype of spastic paraplegia. The human gene implicated in this disease is BSCL2, which encodes a multi-pass transmembrane protein that localizes to the endoplasmic reticulum and is predicted to function in lipid droplet formation and/or metabolism. There is a single orthologous gene in Drosophila, Seipin, for which an amorphic allele and multiple RNAi targeting constructs have been generated. BSCL2 has been implicated in multiple diseases (see OMIM:606158). Many loss-of-function mutations of BSCL2 result in congenital generalized lipodystrophy, type 2 (see OMIM:269700 and FBhh0000447).

UAS constructs of the human gene Hsap\BSCL2 have been introduced into flies, including wild-type and a variant associated with SPG17. Heterologous rescue (functional complementation) has been observed: when expressed in fat body, the wild-type human gene rescues the lipid storage defect of an amorphic Dmel\Seipin mutation.

Variant(s) implicated in human disease tested (as transgenic human gene BSCL2): the S90L (S154L) variant form has been introduced into flies. When expressed in fat body, a human gene carrying the S90L variant has also been found to rescue the phenotypes of an amorphic Dmel\Seipin mutation. This lends support to the hypothesis that S90L is a gain-of-function mutation.

Larvae homozygous for an amorphic mutation of Seipin exhibit reduced lipid storage in fat bodies and ectopic lipid droplets in the salivary glands. Genetic interactions of candidate genes have been assessed based on modification of this phenotype. Multiple physical interactions have been reported; see below and in the Seipin gene report.

[updated Jul. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: spastic paraplegia
Symptoms and phenotype

The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from OMIM:182600; 15.06.29]

Specific Disease Summary: spastic paraplegia 17
OMIM report


Human gene(s) implicated


Symptoms and phenotype

See general description of spastic paraplegia, above.

The first sign of Silver syndrome is usually weakness in the muscles of the hands. These muscles amyotrophy, resulting in abnormal positioning of the thumbs and difficulty using the fingers and hands for tasks such as handwriting. People with Silver syndrome often have high-arched feet (pes cavus) and spasticity in the legs. The signs and symptoms of Silver syndrome typically begin in late childhood but can start anytime from early childhood to late adulthood. The muscle problems associated with Silver syndrome slowly worsen with age, but affected individuals can remain active throughout life. [from Genetics Home Reference, Silver syndrome; 2016.11.29]


Spastic paraplegia-17 (SPG17) is caused by heterozygous mutation in the BSCL2 gene. [from OMIM:270685; 2016.11.29]

Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Silver spastic paraplegia syndrome
Silver syndrome
spastic paraplegia 17, autosomal dominant
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Seipin (Seipin) encodes a transmembrane protein with roles in ER calcium homeostasis and lipid storage. [Date last reviewed: 2019-03-14]
    Molecular function (GO)
      Gene Groups / Pathways
        Comments on ortholog(s)

        Ortholog of human BSCL2 gene (1 Drosophila to 1 human). Dmel\Seipin shares 31% identity and 51% similarity with human BSCL2.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (11 groups)
          Interacting group
          anti tag coimmunoprecipitation, anti tag western blot, electron microscopy
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          split luciferase complementation
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting, western blot
          anti tag coimmunoprecipitation, peptide massfingerprinting
          Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
          Models Based on Experimental Evidence ( 2 )
          Modifiers Based on Experimental Evidence ( 1 )
          is ameliorated by mdyQX25
          is ameliorated by Pcyt116919
          is ameliorated by CdsEY08412
          is exacerbated by mdyQX25
          is exacerbated by Cds1
          is exacerbated by mdyEY07280
          is ameliorated by SCAPEY06708
          is exacerbated by minoEY00734
          is ameliorated by LpinGD14004
          is exacerbated by CdsNIG.7962R
          is ameliorated by mdyEY07280
          Alleles Representing Disease-Implicated Variants
          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
          Publicly Available Stocks
          Selected Drosophila transgenes
          Publicly Available Stocks
          RNAi constructs available
          Publicly Available Stocks
          Selected Drosophila classical alleles
          Allele class
          Publicly Available Stocks
          amorphic allele - molecular evidence
          References (6)