[ZFY27_HUMAN] Defects in ZFYVE27 are the cause of spastic paraplegia autosomal dominant type 33 (SPG33) [MIM:610244]. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Note=According to PubMed:18606302, the properties of the variant Val-191 and its frequency in some populations raise doubts on the implication of that gene in the disease.
[ZFY27_HUMAN] Functions as an upstream inhibitor of RAB11, regulating directional protein transport to the forming neurites. Involved in nerve growth factor-induced neurite formation. May have a more general role in cell projections formation.
↑ Mannan AU, Krawen P, Sauter SM, Boehm J, Chronowska A, Paulus W, Neesen J, Engel W. ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia. Am J Hum Genet. 2006 Aug;79(2):351-7. Epub 2006 Jun 1. PMID:16826525 doi:S0002-9297(07)63142-5
↑ Martignoni M, Riano E, Rugarli EI. The role of ZFYVE27/protrudin in hereditary spastic paraplegia. Am J Hum Genet. 2008 Jul;83(1):127-8; author reply 128-30. doi:, 10.1016/j.ajhg.2008.05.014. PMID:18606302 doi:10.1016/j.ajhg.2008.05.014
↑ Shirane M, Nakayama KI. Protrudin induces neurite formation by directional membrane trafficking. Science. 2006 Nov 3;314(5800):818-21. PMID:17082457 doi:10.1126/science.1134027
↑ Saita S, Shirane M, Natume T, Iemura S, Nakayama KI. Promotion of neurite extension by protrudin requires its interaction with vesicle-associated membrane protein-associated protein. J Biol Chem. 2009 May 15;284(20):13766-77. doi: 10.1074/jbc.M807938200. Epub 2009, Mar 16. PMID:19289470 doi:10.1074/jbc.M807938200