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FB2026_01
,
released March 12, 2026
This report describes spastic paraplegia 15, a subtype of spastic paraplegia that exhibits autosomal recessive inheritance. The human gene implicated is ZFYVE26, which encodes Spastizin, There is one high-scoring fly ortholog, Dmel\Sptz, for which an RNAi-targeting construct and an allele caused by insertional mutagenesis have been generated.
The human ZFYVE26 gene has not been introduced into flies.
Ubiquitous RNAi knockdown of Dmel\Sptz results in locomotor defects, accumulation of autophagosomes, and defects in autophagic lysosome reformation. This model is tractable to screening of potential pharmaceutical treatments.
[updated May 2023 by FlyBase; FBrf0222196]
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 MIM:182600; 15.06.29]
[SPASTIC PARAPLEGIA 15, AUTOSOMAL RECESSIVE; SPG15](https://omim.org/entry/270700)
[ZINC FINGER FYVE DOMAIN-CONTAINING PROTEIN 26; ZFYVE26](https://omim.org/entry/612012)
Spastic paraplegia 15 (SPG15), typically an early-onset complex hereditary spastic paraplegia, is characterized by progressive spasticity that begins in the lower extremities and is associated with several manifestations resulting from central and peripheral nervous system dysfunction. While onset of spasticity is typically in mid- to late childhood or adolescence (i.e., between ages 5 and 18 years), other manifestations, such as developmental delay or learning disability, may be present earlier, often preceding motor involvement. Individuals with adult onset have also been reported. [Gene Reviews, Spastic Paraplegia 15, 2023.05.01]
Spastic paraplegia-15 (SPG15) is an autosomal recessive neurodegenerative disorder characterized by progressive spasticity primarily affecting the lower limbs. It is a complex form of spastic paraplegia, associated with other neurologic dysfunction, including variable intellectual disability, hearing and visual defects, and thin corpus callosum (summary by Goizet et al., 2009, pmid:19805727). [from MIM:270700; 2023.05.01]
Spastic paraplegia 15 (SPG15) is caused by homozygous or compound heterozygous mutation in ZFYVE26, the gene encoding spastizin, on chromosome 14q24. [from MIM:270700; 2023.05.01]
SPG15-related mutations lead to autophagic lysosome reformation defects with lysosome enlargement, free lysosome depletion and autophagosome accumulation (FBrf0255931, Vantaggiato, et al., 2023, pubmed:36029068).
Spastizin, the protein encoded by ZFYVE26, is involved in autophagosome maturation and autophagic lysosome reformation (FBrf0255931, Vantaggiato, et al., 2023, pubmed:36029068).
ZFYVE26 encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. [provided by RefSeq, Oct 2008]
One to one (1 human to 1 Drosophila); ZFYVE26 has one high-scoring Drosophila ortholog, Sptz.
High-scoring ortholog of human ZFYVE26 (1 Drosophila to 1 human).