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WASHC5 gene
URL of this page: https://medlineplus.gov/genetics/gene/washc5/

WASHC5 gene

WASH complex subunit 5

Normal Function

The WASHC5 gene provides instructions for making a protein called strumpellin. Strumpellin is active (expressed) throughout the body. The strumpellin protein has a repeating segment called the spectrin repeat that appears to interact with the structural framework inside cells (the cytoskeleton). Spectrin repeats are found in many different proteins and play an important role in cell structure and cell communication. 

Strumpellin binds to other proteins to form the WASH complex, which is involved in the control of actin proteins. Actin proteins serve many functions within the cell, such as forming a network that provides structural support and transporting molecules within the cell. The WASH complex works with actin proteins to regulate the activity of endosomes, which are structures inside the cell that are involved in sorting, transporting, and recycling proteins and other materials.

Health Conditions Related to Genetic Changes

Spastic paraplegia type 8

Several variants (also called mutations) in the WASHC5 gene have been found to cause spastic paraplegia type 8. This condition belongs to a group of disorders called hereditary spastic paraplegias, which are characterized by progressive muscle stiffness (spasticity) and weakness. Most of the variants that cause spastic paraplegia type 8 change single building blocks (amino acids) in the strumpellin protein, which can alter the structure of the protein. 

Though it is not known exactly how the altered strumpellin protein causes the characteristic features of spastic paraplegia type 8, the changes in the protein likely interfere with the transport of important molecules within the cell.  

More About This Health Condition

Other Disorders

Variants in the WASHC5 gene have been found to cause 3C syndrome (also called Ritscher-Schinzel syndrome), which affects the development of the head, face, brain, and heart. The condition is called 3C syndrome because it affects craniofacial (head and face), cerebellar (brain), and cardiovascular (heart) development. People with 3C syndrome often have Dandy-Walker malformation, which is a structural abnormality of the part of the brain that coordinates movement (cerebellum). Additional signs and symptoms may include an opening in the roof of the mouth (cleft palate), missing pieces of tissue in the structures that form the eye (coloboma), and intellectual disabilities. The condition is found primarily in the First Nations communities in the Canadian provinces of Manitoba and Ontario. The WASHC5 gene variants that cause 3C syndrome affect both copies of the gene and decrease the production of the strumpellin protein. 


Other Names for This Gene

  • KIAA0196
  • RTSC
  • RTSC1
  • SPG8

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Clemen CS, Tangavelou K, Strucksberg KH, Just S, Gaertner L, Regus-Leidig H, Stumpf M, Reimann J, Coras R, Morgan RO, Fernandez MP, Hofmann A, Muller S, Schoser B, Hanisch FG, Rottbauer W, Blumcke I, von Horsten S, Eichinger L, Schroder R. Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases. Brain. 2010 Oct;133(10):2920-41. doi: 10.1093/brain/awq222. Epub 2010 Sep 9. Citation on PubMed
  • Derivery E, Sousa C, Gautier JJ, Lombard B, Loew D, Gautreau A. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Dev Cell. 2009 Nov;17(5):712-23. doi: 10.1016/j.devcel.2009.09.010. Citation on PubMed
  • Djinovic-Carugo K, Gautel M, Ylanne J, Young P. The spectrin repeat: a structural platform for cytoskeletal protein assemblies. FEBS Lett. 2002 Feb 20;513(1):119-23. doi: 10.1016/s0014-5793(01)03304-x. Citation on PubMed
  • Elliott AM, Chudley A. Ritscher-Schinzel Syndrome. 2020 Jan 23. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK553049/ Citation on PubMed
  • Freeman C, Seaman MN, Reid E. The hereditary spastic paraplegia protein strumpellin: characterisation in neurons and of the effect of disease mutations on WASH complex assembly and function. Biochim Biophys Acta. 2013 Jan;1832(1):160-73. doi: 10.1016/j.bbadis.2012.10.011. Epub 2012 Oct 23. Citation on PubMed
  • Hedera P, Rainier S, Alvarado D, Zhao X, Williamson J, Otterud B, Leppert M, Fink JK. Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. Am J Hum Genet. 1999 Feb;64(2):563-9. doi: 10.1086/302258. Citation on PubMed or Free article on PubMed Central
  • Meijer IA, Valdmanis PN, Rouleau GA. Spastic Paraplegia 8. 2008 Aug 13 [updated 2020 May 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1827/ Citation on PubMed
  • Pehrson C, Hertz JM, Wirenfeldt M, Stenager E, Wermuth L, Winther Kristensen B. Hereditary spastic paraplegia type 8: Neuropathological findings. Brain Pathol. 2018 Mar;28(2):292-294. doi: 10.1111/bpa.12494. No abstract available. Citation on PubMed
  • Rocco P, Vainzof M, Froehner SC, Peters MF, Marie SK, Passos-Bueno MR, Zatz M. Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: analysis of muscle beta 1 syntrophin. Am J Med Genet. 2000 May 15;92(2):122-7. doi: 10.1002/(sici)1096-8628(20000515)92:23.0.co;2-b. Citation on PubMed
  • Valdmanis PN, Meijer IA, Reynolds A, Lei A, MacLeod P, Schlesinger D, Zatz M, Reid E, Dion PA, Drapeau P, Rouleau GA. Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia. Am J Hum Genet. 2007 Jan;80(1):152-61. doi: 10.1086/510782. Epub 2006 Dec 1. Citation on PubMed or Free article on PubMed Central

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