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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FA2H
fatty acid 2-hydroxylase
Chromosome 16 Β· 16q23.1
NCBI Gene: 79152Ensembl: ENSG00000103089.10HGNC: HGNC:21197UniProt: Q7L5A8
53PubMed Papers
21Diseases
0Drugs
64Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
fatty acid 2-hydroxylase activityprotein bindingceramide biosynthetic processfree fatty acid 2-hydroxylase activityAutosomal recessive spastic paraplegia type 35hereditary spastic paraplegia 35Spastic paraplegiahereditary spastic paraplegia
✦AI Summary

FA2H (fatty acid 2-hydroxylase) is an enzyme that catalyzes the hydroxylation of free fatty acids at the C-2 position to produce 2-hydroxy fatty acids, which serve as essential building blocks for sphingolipids and glycosphingolipids 1. These 2-hydroxylated sphingolipids are particularly abundant in myelin and skin, where they play critical roles in neural tissue function and epidermal barrier formation 1. The enzyme is stereospecific for producing (R)-2-hydroxy fatty acids and is involved in synthesizing galactosphingolipids of the myelin sheath, as well as sphingolipids in plasma membrane rafts that control lipid raft mobility and protein trafficking 1. FA2H expression is significantly downregulated in inflammatory skin conditions including atopic dermatitis, psoriasis, and seborrheic dermatitis, indicating its importance in maintaining skin barrier function 23. Mutations in FA2H cause hereditary spastic paraplegia 35 (HSP35/SPG35), also known as fatty acid hydroxylase-associated neurodegeneration (FAHN), a rare neurodegenerative disorder classified under neurodegeneration with brain iron accumulation (NBIA) 456. The gene's role extends beyond neurological function, as FA2H expression correlates with cancer prognosis and is involved in metabolic vulnerabilities in pancreatic cancer, where it participates in sulfatide biosynthesis pathways 17.

Sources cited
1
FA2H catalyzes hydroxylation of fatty acids at C-2 position, produces 2-hydroxy fatty acids for sphingolipid synthesis, abundant in myelin and skin, causes HSP35/FAHN when deficient
PMID: 36902339
2
FA2H is significantly downregulated in atopic dermatitis and psoriasis lesional skin
PMID: 32709423
3
FA2H downregulation observed in seborrheic dermatitis
PMID: 39900186
4
FA2H mutations cause hereditary spastic paraplegia type 35 (SPG35)
PMID: 23897027
5
FA2H mutations cause fatty acid hydroxylase-associated neurodegeneration, an ultrarare NBIA disorder
PMID: 29325618
6
FA2H-associated neurodegeneration (FAHN) is classified under neurodegeneration with brain iron accumulation disorders
PMID: 40603798
7
FA2H involved in sulfatide biosynthesis pathways and metabolic vulnerabilities in pancreatic cancer
PMID: 40268349
Disease Associationsβ“˜21
Autosomal recessive spastic paraplegia type 35Open Targets
0.84Strong
hereditary spastic paraplegia 35Open Targets
0.83Strong
Spastic paraplegiaOpen Targets
0.64Moderate
hereditary spastic paraplegiaOpen Targets
0.56Moderate
fatty acid hydroxylase-associated neurodegenerationOpen Targets
0.56Moderate
DystoniaOpen Targets
0.46Moderate
neurodegeneration with brain iron accumulationOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.45Moderate
Intellectual disabilityOpen Targets
0.34Weak
diabetic ketoacidosisOpen Targets
0.32Weak
vascular diseaseOpen Targets
0.32Weak
frozen shoulderOpen Targets
0.31Weak
atrophic gastritisOpen Targets
0.28Weak
spastic ataxiaOpen Targets
0.27Weak
Cerebellar atrophyOpen Targets
0.26Weak
Tip-toe gaitOpen Targets
0.26Weak
bronchial diseaseOpen Targets
0.24Weak
Non-Neoplastic Bile Duct DisorderOpen Targets
0.13Weak
Alopecia-intellectual disability syndromeOpen Targets
0.10Weak
Alopecia universalisOpen Targets
0.10Suggestive
Spastic paraplegia 35, autosomal recessive, with or without neurodegenerationUniProt
Pathogenic Variants64
NM_024306.5(FA2H):c.911dup (p.Leu305fs)Pathogenic
Hereditary spastic paraplegia 35|Spastic paraplegia
β˜…β˜…β˜†β˜†2026β†’ Residue 305
NM_024306.5(FA2H):c.159_176del (p.Arg53_Ile58del)Pathogenic
Hereditary spastic paraplegia 35|not provided|Spastic paraplegia
β˜…β˜…β˜†β˜†2025β†’ Residue 53
NM_024306.5(FA2H):c.510_511del (p.Tyr170_Ser171delinsTer)Pathogenic
Hereditary spastic paraplegia 35|Spastic paraplegia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 170
NM_024306.5(FA2H):c.131C>A (p.Pro44Gln)Pathogenic
Spastic paraplegia|Neurodegeneration with brain iron accumulation|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 44
NM_024306.5(FA2H):c.1A>G (p.Met1Val)Pathogenic
Spastic paraplegia|Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_024306.5(FA2H):c.379C>T (p.Arg127Ter)Pathogenic
not provided|Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2025β†’ Residue 127
NM_024306.5(FA2H):c.443C>T (p.Pro148Leu)Pathogenic
Spastic paraplegia|Inborn genetic diseases|not provided|Neurodegeneration with brain iron accumulation|Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2025β†’ Residue 148
NM_024306.5(FA2H):c.786+1G>APathogenic
Hereditary spastic paraplegia 35|not provided
β˜…β˜…β˜†β˜†2025
NM_024306.5(FA2H):c.130C>T (p.Pro44Ser)Pathogenic
not provided|Hereditary spastic paraplegia 35|Spastic paraplegia
β˜…β˜…β˜†β˜†2025β†’ Residue 44
NM_024306.5(FA2H):c.888del (p.Gly298fs)Pathogenic
Spastic paraplegia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 298
NM_024306.5(FA2H):c.704G>A (p.Arg235His)Pathogenic
Hereditary spastic paraplegia 35|Spastic paraplegia
β˜…β˜…β˜†β˜†2025β†’ Residue 235
NM_024306.5(FA2H):c.620C>T (p.Thr207Met)Pathogenic
Hereditary spastic paraplegia|Hereditary spastic paraplegia 35|Spastic paraplegia
β˜…β˜…β˜†β˜†2025β†’ Residue 207
NM_024306.5(FA2H):c.941_945del (p.Thr314fs)Pathogenic
Spastic paraplegia|Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2025β†’ Residue 314
NM_024306.5(FA2H):c.131del (p.Pro44fs)Pathogenic
Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2025β†’ Residue 44
NM_024306.5(FA2H):c.806G>A (p.Arg269His)Pathogenic
Spastic paraplegia|Hereditary spastic paraplegia 35|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 269
NM_024306.5(FA2H):c.340_363+8delPathogenic
Hereditary spastic paraplegia 35|Spastic paraplegia|not provided
β˜…β˜…β˜†β˜†2024
NM_024306.5(FA2H):c.822del (p.Val275fs)Pathogenic
Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2024β†’ Residue 275
NM_024306.5(FA2H):c.589C>T (p.Arg197Ter)Pathogenic
Spastic paraplegia|not provided|Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2024β†’ Residue 197
NM_024306.5(FA2H):c.565C>T (p.Arg189Ter)Pathogenic
Inborn genetic diseases|Hereditary spastic paraplegia|Hereditary spastic paraplegia 35|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 189
NM_024306.5(FA2H):c.363+2T>CPathogenic
Hereditary spastic paraplegia 35
β˜…β˜…β˜†β˜†2023
View on ClinVar β†—
Related Genes
AGMOProtein interaction94%C19orf12Protein interaction85%FAXDC2Protein interaction80%ALDH3A2Protein interaction78%MSMO1Protein interaction78%DCAF17Protein interaction72%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
9%
Lung
2%
Liver
1%
Heart
1%
Ovary
0%
Gene Interaction Network
Click a node to explore
FA2HAGMOC19orf12FAXDC2ALDH3A2MSMO1DCAF17
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q7L5A8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.76LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.51 [0.35–0.76]
RankingsWhere FA2H stands among ~20K protein-coding genes
  • #8,423of 20,598
    Most Researched53
  • #1,120of 5,498
    Most Pathogenic Variants64 Β· top quartile
  • #6,069of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedFA2H
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Neurodegeneration with brain iron accumulation.
PMID: 29325618
Handb Clin Neurol Β· 2018
1.00
2
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
PMID: 23897027
Acta Neuropathol Β· 2013
0.90
3
Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis.
PMID: 32709423
J Allergy Clin Immunol Β· 2021
0.80
4
Long-chain sulfatide enrichment is an actionable metabolic vulnerability in intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic cancers.
PMID: 40268349
Gut Β· 2025
0.70
5
Neurodegeneration with Brain Iron Accumulation.
PMID: 40603798
Adv Exp Med Biol Β· 2025
0.60