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General Information
Name
amyotrophic lateral sclerosis (postulated), TAF15-related
FlyBase ID
FBhh0000407
Disease Ontology Term
Parent Disease
OMIM
Overview

The human gene TAF15 is proposed as a causative gene of amyotrophic lateral sclerosis. TAF15 was initially identified as a candidate in a yeast functional screen of human genes carrying RNA recognition motifs and prion-like domains; subsequent genome sequence analysis of patients with ALS support this association (FBrf0217025). It is proposed that that aggregation-prone RNA-binding proteins might generally contribute to ALS pathogenesis. TAF15 is one of multiple human genes orthologous to the Drosophila gene caz; the others are FUS (implicated in ALS6, FBhh0000018) and EWSR1 (FBhh0000408). A second orthologous gene in flies, CG14718, appears to be expressed exclusively in testis.

Multiple different UAS constructs of the human Hsap\TAF15 gene have been introduced into flies, including wild-type and genes carrying putative mutational lesions found in ALS patients. Variant(s) implicated in human disease tested (as transgenic human gene, TAF15): G391E and R408C variant forms of the human gene have been introduced into flies.

For loss-of-function mutations in the Dmel\caz gene, observed phenotypes include aspects similar to ALS, including locomotor defects, defects in synaptic transmission, and reduced lifespan. Physical and genetic interactions of Dmel\caz have been described; see below and in the caz gene report.

[updated Jul. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: amyotrophic lateral sclerosis
Symptoms and phenotype

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. [from OMIM:105400, 2015.02.11]

Specific Disease Summary: amyotrophic lateral sclerosis (postulated), TAF15-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). [from OMIM:105400, 2016.10.11]

Genetics

Translocations involving TAF15 play a role in acute leukemia and extraskeletal myxoid chondrosarcoma. [Gene Cards, TAF15; 2016.10.11]

Cellular phenotype and pathology
Molecular information

TAF15 (TATA-Box Binding Protein Associated Factor 15) encodes an RNA-binding protein that contributes to transcription initiation at specific promoters as a component of a subset of multi-subunit transcription initiation factor TFIID complexes. [Gene Cards, TAF15; 2016.10.11]

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 many (3 human to 2 Drosophila); additional human orthologs are FUS and EWSR1.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    cabeza (caz) encodes a chromatin binding protein involved in locomotion, synaptic growth at the neuromuscular junction and eye development. [Date last reviewed: 2019-03-28]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-to moderate-scoring ortholog of human genes FUS and EWSR1; lower-scoring ortholog of TAF15 (2 Drosophila to 3 human). Dmel\caz shares 40-42% identity and 50-51% similarity with the human genes FUS and EWSR1; TAF15 is less similar.

    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 (10 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti bait coimmunoprecipitation, western blot
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      RNA-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, quantitative reverse transcription pcr
      anti tag coimmunoprecipitation, quantitative reverse transcription pcr
      Alleles Reported to Model Human Disease (Disease Ontology) (20 alleles)
      Models Based on Experimental Evidence ( 3 )
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 15 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 8 )
      Allele
      Disease
      Interaction
      References
      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
      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
      P-element activity
      amorphic allele - molecular evidence
      Delta2-3 transposase
      amorphic allele - molecular evidence
      ends-out gene targeting
      phiC31 integrase
      phiC31 integrase
      P-element activity
      amorphic allele - molecular evidence
      Delta2-3 transposase
      amorphic allele - molecular evidence
      ends-out gene targeting
      phiC31 integrase
      phiC31 integrase
      References (7)