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]
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]
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]
Translocations involving TAF15 play a role in acute leukemia and extraskeletal myxoid chondrosarcoma. [Gene Cards, TAF15; 2016.10.11]
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]
Many to many (3 human to 2 Drosophila); additional human orthologs are FUS and EWSR1.
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.