FA2H (Fatty Acid 2-Hydroxylase) Gene
Key enzyme in myelin synthesis and sphingolipid metabolism; mutations cause leukodystrophy and spastic paraplegia
Gene Information Card
| Symbol | FA2H |
|---|---|
| Full Name | Fatty Acid 2-Hydroxylase |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.1 |
| NCBI Gene ID | 79152 ncbi.nlm.nih.gov/gene/79152 |
| Ensembl ID | ENSG00000103089 |
| UniProt ID | Q7L5A8 |
| OMIM ID | 611026 |
| HGNC ID | 21197 |
| Aliases | FAAH, FA2H1, FA2H2, SPG35 |
Description
The FA2H gene encodes fatty acid 2-hydroxylase, an enzyme that catalyzes the 2-hydroxylation of free fatty acids, primarily producing 2-hydroxy sphingolipids. This modification is essential for the stability and function of myelin sheaths in the central and peripheral nervous systems. FA2H is highly expressed in the brain and is critical for normal myelination. Loss-of-function mutations lead to progressive neurodegeneration, including hereditary spastic paraplegia type 35 (SPG35) and leukodystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia 35 (SPG35) | Loss-of-function mutations impair 2-hydroxylation of fatty acids, disrupting myelin maintenance and leading to axonal degeneration in corticospinal tracts. | ClinVar, OMIM |
| Leukodystrophy, Hypomyelinating, 5 (HLD5) | Deficient 2-hydroxy sphingolipid synthesis causes hypomyelination and white matter abnormalities in the brain. | ClinVar, OMIM |
| Neurodegeneration with Brain Iron Accumulation (NBIA) | FA2H mutations may disrupt lipid metabolism, contributing to iron deposition and neuronal death. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Spinal Cord | 8.2 | Medium |
| Testis | 4.1 | Low |
| Kidney | 3.0 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.3 | Neuronal model |
| U-87 MG (glioblastoma) | 7.8 | Glial model |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.509C>T (p.Thr170Met) | Missense | Rare | Loss of function; reduced enzyme activity |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of function; initiation codon disrupted |
| c.706C>T (p.Arg236*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1135C>T (p.Arg379Cys) | Missense | Rare | Loss of function; impaired catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most FA2H mutations are loss-of-function, reducing or abolishing 2-hydroxylase activity, leading to deficient 2-hydroxy sphingolipids and myelin instability.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • fatty acid metabolic process (GO:0006631) | • lipid biosynthetic process (GO:0008610) |
| • integral component of membrane (GO:0016021) | • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016717) |
| • sphingolipid biosynthetic process (GO:0042765) | • myelination (GO:0042552) |
Pathways
• Sphingolipid metabolism (Reactome: R-HSA-428157)
• Fatty acid metabolism (KEGG: hsa00071)
• Myelin sheath formation (Reactome: R-HSA-9617174)
Protein Summary
Fatty acid 2-hydroxylase (FA2H) is a 372-amino acid integral membrane protein localized to the endoplasmic reticulum. It belongs to the fatty acid hydroxylase family and uses molecular oxygen and NAD(P)H to catalyze the 2-hydroxylation of free fatty acids, which are then incorporated into ceramides and sphingolipids. 2-Hydroxy sphingolipids are enriched in myelin and contribute to membrane stability and lipid raft organization. FA2H is highly expressed in oligodendrocytes and Schwann cells. Mutations cause autosomal recessive neurological disorders characterized by spasticity, ataxia, and white matter degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FA2H Knockout HEK293 Cell Line | EDJ-KQ11983 | Human | 79152 | Details Get a Quote |
| FA2H Knockout A-549 Cell Line | EDJ-KQ40552 | Human | 79152 | Details Get a Quote |
| FA2H Knockout HCT 116 Cell Line | EDJ-KQ40553 | Human | 79152 | Details Get a Quote |
| FA2H Knockout HeLa Cell Line | EDJ-KQ57150 | Human | 79152 | Details Get a Quote |
