FA2H Gene

HGNC Family	Fatty acid hydroxylase domain containing
Name	fatty acid 2-hydroxylase
Description	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. Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia.[provided by RefSeq, Mar 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fatty acid 2‐hydroxylase (FA2H) is an enzyme that catalyzes the 2‐hydroxylation of fatty acids—a modification essential for the synthesis of key sphingolipids. In the central nervous system, FA2H converts free fatty acids into 2‐hydroxy fatty acids that are subsequently incorporated into galactosylceramide and sulfatide, two major myelin lipids. This modification is critical for normal myelin formation, maintenance, and function, and its disruption is linked to a spectrum of neurodegenerative disorders including complex spastic paraplegia (SPG35), leukodystrophy, and neurodegeneration with brain iron accumulation (2,3,4,5,6,7,8,13,10,11)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In animal models, loss of FA2H function leads to demyelination, axonal degeneration, and deficits in neural performance—findings that underscore the enzyme’s cell‐autonomous role in oligodendrocytes as well as potential functions in other central nervous system cell types (6,7,8). In addition to its established role in myelin, FA2H also contributes to skin homeostasis by generating α‐hydroxylated ceramides that are required for proper formation of the epidermal permeability barrier; deficiencies in FA2H can perturb the structure and function of sebaceous glands and the skin barrier (14)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Recent studies further implicate FA2H in metabolic regulation. For instance, manipulation of FA2H levels—either via microRNAs (such as miR‐3075) or by exogenous compounds like Δ(9)‐tetrahydrocannabinol (Δ9‐THC)—has been shown to modulate lipid profiles, affect adipocyte differentiation, and influence insulin sensitivity (9,12,15). Collectively, these observations reveal that FA2H serves as a critical modulator of lipid metabolism in both neural and peripheral tissues. Its multifaceted role in ensuring proper myelin integrity, maintaining skin barrier function, and regulating metabolic processes highlights its potential as a target for therapeutic intervention in a host of neurodegenerative and metabolic disorders.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n References:."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eleanna Kara, Arianna Tucci, Claudia Manzoni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and phenotypic characterization of complex hereditary spastic paraplegia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/aww111"}], "href": "https://doi.org/10.1093/brain/aww111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27217339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27217339"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Simon Edvardson, Hiroko Hama, Avraham Shaag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.10.010"}], "href": "https://doi.org/10.1016/j.ajhg.2008.10.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19068277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19068277"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Katherine J Dick, Matthias Eckhardt, Coro Paisán-Ruiz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21205"}], "href": "https://doi.org/10.1002/humu.21205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20104589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20104589"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nathan L Alderson, Barbara M Rembiesa, Michael D Walla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human FA2H gene encodes a fatty acid 2-hydroxylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406649200"}], "href": "https://doi.org/10.1074/jbc.M406649200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15337768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15337768"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthias Eckhardt, Afshin Yaghootfam, Simon N Fewou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20041451"}], "href": "https://doi.org/10.1042/BJ20041451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15658937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15658937"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kathleen A Potter, Michael J Kern, George Fullbright, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Central nervous system dysfunction in a mouse model of FA2H deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.21172"}], "href": "https://doi.org/10.1002/glia.21172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21491498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21491498"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Caterina Garone, Tommaso Pippucci, Duccio M Cordelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Med Child Neurol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1469-8749.2011.03993.x"}], "href": "https://doi.org/10.1111/j.1469-8749.2011.03993.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21592092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21592092"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Phyllis Dan, Simon Edvardson, Jacek Bielawski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lipids Health Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-511X-10-84"}], "href": "https://doi.org/10.1186/1476-511X-10-84"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21599921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21599921"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shuso Takeda, Eriko Ikeda, Shengzhong Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tox.2014.09.011"}], "href": "https://doi.org/10.1016/j.tox.2014.09.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25291031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25291031"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Li Cao, Xiao-Jun Huang, Chan-Juan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A rare family with Hereditary Spastic Paraplegia Type 35 due to novel FA2H mutations: a case report with literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2013.02.026"}], "href": "https://doi.org/10.1016/j.jns.2013.02.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23566484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23566484"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Francesco Mari, Beatrice Berti, Alessandro Romano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and neuroimaging features of autosomal recessive spastic paraplegia 35 (SPG35): case reports, new mutations, and brief literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-018-0538-8"}], "href": "https://doi.org/10.1007/s10048-018-0538-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29423566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29423566"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Nathan L Alderson, Eduardo N Maldonado, Michael J Kern, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M600362-JLR200"}], "href": "https://doi.org/10.1194/jlr.M600362-JLR200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16998236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16998236"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Helena Maier, Marion Meixner, Dieter Hartmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Normal fur development and sebum production depends on fatty acid 2-hydroxylase expression in sebaceous glands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.231977"}], "href": "https://doi.org/10.1074/jbc.M111.231977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21628453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21628453"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Lin Guo, Dequan Zhou, Kenneth M Pryse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fatty acid 2-hydroxylase mediates diffusional mobility of Raft-associated lipids, GLUT4 level, and lipogenesis in 3T3-L1 adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.119933"}], "href": "https://doi.org/10.1074/jbc.M110.119933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20519515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20519515"}]}]}]}
Synonyms	FAH1, SCS7, SPG35, FAXDC1, FAAH
Proteins	FA2H_HUMAN
NCBI Gene ID	79152
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FA2H has 6,908 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for FA2H from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FA2H Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FA2H gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of FA2H gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of FA2H gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of FA2H gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FA2H gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of FA2H gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FA2H gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FA2H gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of FA2H gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FA2H gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of FA2H gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FA2H gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FA2H gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FA2H gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of FA2H gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with FA2H gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with FA2H gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FA2H gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FA2H protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FA2H protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with FA2H protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with FA2H protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of FA2H gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FA2H gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FA2H gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FA2H gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by FA2H gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving FA2H gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving FA2H gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with FA2H gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with FA2H gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with FA2H gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with FA2H gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FA2H gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at FA2H gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FA2H gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FA2H gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing FA2H from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with FA2H gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of FA2H gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.