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FA2H

From Wikipedia, the free encyclopedia
FA2H
Identifiers
AliasesFA2H, FAAH, FAH1, FAXDC1, SCS7, SPG35, fatty acid 2-hydroxylase
External IDsOMIM: 611026; MGI: 2443327; HomoloGene: 56284; GeneCards: FA2H; OMA:FA2H - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_024306

NM_178086

RefSeq (protein)

NP_077282

NP_835187

Location (UCSC)Chr 16: 74.71 – 74.77 MbChr 8: 112.07 – 112.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fatty acid 2-hydroxylase is a protein that in humans is encoded by the FA2H gene.[5]

Function

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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.[5]

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

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Mutations in this gene have been associated with leukodystrophy dysmyelinating with hereditary spastic paraplegia type 35 (SPG35) with or without dystonia[5] as well as fatty acid hydroxylase-associated neurodegeneration.[6] 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.[7]

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.[8]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000103089Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033579Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c "Entrez Gene: Fatty acid 2-hydroxylase". Retrieved 2011-12-30.
  6. ^ Pierson TM, Simeonov DR, Sincan M, Adams DA, Markello T, Golas G, et al. (April 2012). "Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration". European Journal of Human Genetics. 20 (4): 476–9. doi:10.1038/ejhg.2011.222. PMC 3306865. PMID 22146942.
  7. ^ Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, Söhn AS, et al. (June 2019). "FAHN/SPG35: a narrow phenotypic spectrum across disease classifications". Brain. 142 (6): 1561–1572. doi:10.1093/brain/awz102. PMC 6536916. PMID 31135052.
  8. ^ Takeda S, Harada M, Su S, Okajima S, Miyoshi H, Yoshida K, Nishimura H, Okamoto Y, Amamoto T, Watanabe K, Omiecinski CJ, Aramaki H (2013). "Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ(9)-tetrahydrocannabinol in human breast cancer cells". The Journal of Toxicological Sciences. 38 (2): 305–8. doi:10.2131/jts.38.305. PMC 4018719. PMID 23535410.

Further reading

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