This report describes spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, a neurologic disorder characterized by onset of gait disturbances. The human gene implicated is TDP1, which encodes tyrosyl-DNA phosphodiesterase 1. There is one high-scoring fly ortholog, Dmel\gkt, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Human TDP1 has not been introduced into flies.
Mushroom body-specific RNAi knockdown of Dmel\gkt significantly affects both startle-induced and spontaneous motor behavior.
[updated Jun. 2024 by FlyBase; FBrf0222196]
Spinocerebellar ataxia with axonal neuropathy is an autosomal recessive neuromuscular disorder typically characterized by onset in the first or second decade of gait disturbance, slowly progressive distal muscle weakness, and axonal sensorimotor neuropathy with distal sensory impairment. [from MIM:218387, MIM:607250; 2020.07.14]
[SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE, WITH AXONAL NEUROPATHY 1; SCAN1](https://omim.org/entry/607250)
[TYROSYL-DNA PHOSPHODIESTERASE 1; TDP1](https://omim.org/entry/607198)
Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is an autosomal recessive neurologic disorder characterized by onset of gait disturbances in the first or second decades of life. Affected individuals have cerebellar ataxia associated with cerebellar atrophy on brain imaging, as well as an axonal sensorimotor neuropathy with distal sensory impairment, hypo- or areflexia, pes cavus, and steppage gait (summary by Takashima et al., 2002, pubmed:12244316). [from MIM:607250; 2024.06.05]
Ataxia-telangiectasia-like disorder-1 (ATLD1) is caused by homozygous mutation in the TDP1 gene on chromosome 14q31. [from MIM:607250; 2024.06.05]
TDP1 encodes Tyrosyl-DNA Phosphodiesterase 1, a protein involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. [provided by RefSeq, Aug 2016]
One to one (1 human to 1 Drosophila); TDP1 has one high-scoring Drosophila ortholog, gkt.
High-scoring ortholog of human TDP1 (1 Drosophila to 1 human).
