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FB2026_01
,
released March 12, 2026
It has been postulated that the human gene UFM1 (ubiquitin fold modifier 1) is implicated in the development of autosomal recessive spinocerebellar ataxia. UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 and E2-like conjugating enzyme UFC1 in a manner analogous to ubiquitylation. There is a single orthologous gene in Drosophila, Dmel\Ufm1, for which RNAi-targeting constructs have been generated. UFM1 has also been implicated in the neurodevelopmental disorder hypomyelinating leukodystrophy 14 (MIM:617899).
Several genes (UFM1, UBA5, and UFC1) that have roles in a common ubiquitination-like post-translational-modification process have been tentatively implicated in development of autosomal recessive spinocerebellar ataxia (see also FBhh0000613 and FBhh0000614). In flies, RNAi-effected knockdown of any of the three orthologous genes results in similar phenotypes.
The human UFM1 gene has not been introduced into flies.
Ubiquitous knockdown of Dmel\Ufm1 effected by RNAi results in adults with visible phenotypes, locomotor defects, and shortened lifespan. Neuron-specific knockdown results in neuroanatomical defects in larval neuromuscular junctions. Physical interactions of Dmel\Ufm1 have been described; see below and in the Ufm1 gene report.
[updated Jan. 2019 by FlyBase; FBrf0222196]
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years (Palau and Espinos, 2006; pubmed:17112370).
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. [from Gene Reviews, Hereditary Ataxia Overview; pubmed:20301317; 2017.06.16]
See also Jayadev and Bird, 2013 (pubmed:23538602).
Autosomal recessive spinocerebellar ataxia is a neurologic disorder characterized by onset of progressive gait difficulties, eye movement abnormalities, and dysarthria in the first or second decade of life (summary, Dy et al, 2105; pubmed:26224725). [from MIM:609270; 2020.07.13]
UFM1, UBA5, and UFC1 have roles in a common ubiquitination-like post-translational-modification process: UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 and E2-like conjugating enzyme UFC1 in a manner analogous to ubiquitylation. This post-translational modification of proteins may play a crucial role in a number of cellular processes, such as nuclear receptors-mediated transcription and the cellular response to endoplasmic reticulum stress. [Gene Cards, UFM1; 2017.09.13]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human gene UFM1 (1 Drosophila to 1 human); Dmel\Ufm1 shares 89% identity and 95% similarity with the human gene.