FA2H

FA2H
Identifiers
Aliases	FA2H, FAAH, FAH1, FAXDC1, SCS7, SPG35, fatty acid 2-hydroxylase
External IDs	OMIM: 611026; MGI: 2443327; HomoloGene: 56284; GeneCards: FA2H; OMA:FA2H - orthologs
Gene location (Human) Chr. Chromosome 16 (human) Band 16q23.1 Start 74,712,955 bp End 74,774,831 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8|8 E1 Start 112,071,767 bp End 112,120,456 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in C1 segment corpus callosum inferior olivary nucleus inferior ganglion of vagus nerve dorsal motor nucleus of vagus nerve optic nerve olfactory bulb subthalamic nucleus sural nerve substantia nigra Top expressed in skin of external ear lip sciatic nerve epithelium of stomach transitional epithelium of urinary bladder deep cerebellar nuclei pontine nuclei pyloric antrum ventral tegmental area zygote More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding metal ion binding heme binding oxidoreductase activity fatty acid alpha-hydroxylase activity Cellular component integral component of membrane organelle membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle endoplasmic reticulum Biological process central nervous system myelin maintenance lipid modification peripheral nervous system myelin maintenance lipid metabolism sphingolipid biosynthetic process fatty acid metabolic process fatty acid biosynthetic process regulation of cell population proliferation regulation of hair cycle sebaceous gland cell differentiation lipid biosynthetic process glucosylceramide biosynthetic process galactosylceramide biosynthetic process plasma membrane raft organization ceramide biosynthetic process establishment of skin barrier Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79152 338521 Ensembl ENSG00000103089 ENSMUSG00000033579 UniProt Q7L5A8 Q5MPP0 RefSeq (mRNA) NM_024306 NM_178086 RefSeq (protein) NP_077282 NP_835187 Location (UCSC) Chr 16: 74.71 – 74.77 Mb Chr 8: 112.07 – 112.12 Mb PubMed search
Wikidata
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Fatty acid 2-hydroxylase is a protein that in humans is encoded by the FA2H gene.

Function

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.

Mechanism 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 hereditary spastic paraplegia type 35 (SPG35) with or without dystonia as well as fatty acid hydroxylase-associated neurodegeneration. The largest cohort with a detailed phenotypical description and a highly sensitive imaging phenotype ('WHAT'- acronym for: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum) was recently published.

FA2H has been shown to modulate cell differentiation in vitro. FA2H is may be a Δ⁹-THC-regulated gene, as Δ⁹-THC induces differentiation signal(s) in poorly differentiated MDA-MB-231 cells.

Further reading

• Alderson NL, Rembiesa BM, Walla MD, Bielawska A, Bielawski J, Hama H (November 2004). "The human FA2H gene encodes a fatty acid 2-hydroxylase". The Journal of Biological Chemistry. 279 (47): 48562–8. doi:10.1074/jbc.M406649200. PMID 15337768.
• Uchida Y, Hama H, Alderson NL, Douangpanya S, Wang Y, Crumrine DA, Elias PM, Holleran WM (May 2007). "Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation". The Journal of Biological Chemistry. 282 (18): 13211–9. doi:10.1074/jbc.M611562200. PMID 17355976.
• Dick KJ, Al-Mjeni R, Baskir W, Koul R, Simpson MA, Patton MA, Raeburn S, Crosby AH (July 2008). "A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23". Neurology. 71 (4): 248–52. doi:10.1212/01.wnl.0000319610.29522.8a. PMID 18463364. S2CID 207102944.
• Edvardson S, Hama H, Shaag A, Gomori JM, Berger I, Soffer D, Korman SH, Taustein I, Saada A, Elpeleg O (November 2008). "Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia". American Journal of Human Genetics. 83 (5): 643–8. doi:10.1016/j.ajhg.2008.10.010. PMC 2668027. PMID 19068277.
• Wheeler HE, Metter EJ, Tanaka T, Absher D, Higgins J, Zahn JM, Wilhelmy J, Davis RW, Singleton A, Myers RM, Ferrucci L, Kim SK (October 2009). Gibson G (ed.). "Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging". PLOS Genetics. 5 (10): e1000685. doi:10.1371/journal.pgen.1000685. PMC 2752811. PMID 19834535.
• Dastani Z, Pajukanta P, Marcil M, Rudzicz N, Ruel I, Bailey SD, Lee JC, Lemire M, Faith J, Platko J, Rioux J, Hudson TJ, Gaudet D, Engert JC, Genest J (March 2010). "Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects". European Journal of Human Genetics. 18 (3): 342–7. doi:10.1038/ejhg.2009.157. PMC 2824775. PMID 19844255.
• Dick KJ, Eckhardt M, Paisán-Ruiz C, Alshehhi AA, Proukakis C, Sibtain NA, Maier H, Sharifi R, Patton MA, Bashir W, Koul R, Raeburn S, Gieselmann V, Houlden H, Crosby AH (April 2010). "Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35)". Human Mutation. 31 (4): E1251-60. doi:10.1002/humu.21205. PMID 20104589. S2CID 5344306.
• Dan P, Edvardson S, Bielawski J, Hama H, Saada A (May 2011). "2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase". Lipids in Health and Disease. 10: 84. doi:10.1186/1476-511X-10-84. PMC 3107802. PMID 21599921.