This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups.[1]
File:2-OH sphingolipid synthesis.pdfMechanism of 2-hydroxylated sphingolipid generation. Essentially they are generated like their non-hydroxylated counterparts. The only difference is that fatty acids are hydroxylated by fatty acid 2-hydroxylase (FA2H) before being incorporated into dihydroceramide by ceramide synthases (CerS).
Clinical significance
Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia[1] as well as fatty acid hydroxylase-associated neurodegeneration.[2]
↑Pierson TM, Simeonov DR, Sincan M, Adams DA, Markello T, Golas G, Fuentes-Fajardo K, Hansen NF, Cherukuri PF, Cruz P, Blackstone C, Tifft C, Boerkoel CF, Gahl WA (December 2011). "Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration". Eur. J. Hum. Genet. 20 (4): 476–9. doi:10.1038/ejhg.2011.222. PMID22146942.
Further reading
Alderson, N. L.; Rembiesa, B. M.; Walla, M. D.; Bielawska, A.; Bielawski, J.; Hama, H. (2004). "The Human FA2H Gene Encodes a Fatty Acid 2-Hydroxylase". Journal of Biological Chemistry. 279 (47): 48562–48568. doi:10.1074/jbc.M406649200. PMID15337768.
Uchida, Y.; Hama, H.; Alderson, N. L.; Douangpanya, S.; Wang, Y.; Crumrine, D. A.; Elias, P. M.; Holleran, W. M. (2007). "Fatty Acid 2-Hydroxylase, Encoded by FA2H, Accounts for Differentiation-associated Increase in 2-OH Ceramides during Keratinocyte Differentiation". Journal of Biological Chemistry. 282 (18): 13211–13219. doi:10.1074/jbc.M611562200. PMID17355976.
Dick, K. J.; Al-Mjeni, R.; Baskir, W.; Koul, R.; Simpson, M. A.; Patton, M. A.; Raeburn, S.; Crosby, A. H. (2008). "A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23". Neurology. 71 (4): 248–252. doi:10.1212/01.wnl.0000319610.29522.8a. PMID18463364.
Dick, K. J.; Eckhardt, M.; Paisán-Ruiz, C.; Alshehhi, A. A.; Proukakis, C.; Sibtain, N. A.; Maier, H.; Sharifi, R.; Patton, M. A.; Bashir, W.; Koul, R.; Raeburn, S.; Gieselmann, V.; Houlden, H.; Crosby, A. H. (2010). "Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35)". Human Mutation. 31 (4): E1251–E1260. doi:10.1002/humu.21205. PMID20104589.
