FA2H

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.

Fatty Acid 2-Hydroxylase

Catalyzes the hydroxylation of free fatty acids at the C-2 position to produce 2-hydroxy fatty acids, which are building blocks of sphingolipids and glycosphingolipids common in neural tissue and epidermis (PubMed:15337768, PubMed:15863841, PubMed:17355976, PubMed:22517924).

FA2H is stereospecific for the production of (R)-2-hydroxy fatty acids (PubMed:22517924).

Plays an essential role in the synthesis of galactosphingolipids of the myelin sheath (By similarity).

Responsible for the synthesis of sphingolipids and glycosphingolipids involved in the formation of epidermal lamellar bodies critical for skin permeability barrier (PubMed:17355976).

Participates in the synthesis of glycosphingolipids and a fraction of type II wax diesters in sebaceous gland, specifically regulating hair follicle homeostasis (By similarity).

Involved in the synthesis of sphingolipids of plasma membrane rafts, controlling lipid raft mobility and trafficking of raft-associated proteins (By similarity).

Central nervous system myelin maintenance Source: Ensembl
Ceramide biosynthetic process Source: UniProtKB
Establishment of skin barrier Source: UniProtKB
Fatty acid biosynthetic process Source: UniProtKB-KW
Fatty acid metabolic process Source: GO_Central
Galactosylceramide biosynthetic process Source: UniProtKB
Glucosylceramide biosynthetic process Source: UniProtKB
Lipid modification Source: Ensembl
Peripheral nervous system myelin maintenance Source: Ensembl
Plasma membrane raft organization Source: UniProtKB
Regulation of cell population proliferation Source: Ensembl
Regulation of hair cycle Source: Ensembl
Sebaceous gland cell differentiation Source: Ensembl
Sphingolipid biosynthetic process Source: Reactome

Endoplasmic reticulum membrane; Microsome membrane

Spastic paraplegia 35, autosomal recessive (SPG35):
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur.