DEGS1 (Sphingolipid Delta(4)-Desaturase) Gene: Function, Mutations, and Related Diseases
Comprehensive biomedical resource on DEGS1, including gene structure, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | DEGS1 |
|---|---|
| Full Name | Delta(4)-desaturase, sphingolipid 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.12 |
| NCBI Gene ID | 8560 ncbi.nlm.nih.gov/gene/8560 |
| Ensembl ID | ENSG00000143753 |
| UniProt ID | O15121 |
| OMIM ID | 610828 |
| HGNC ID | 2848 |
| Aliases | DES1, FADS7, MLD, MGC5073 |
Description
DEGS1 encodes the enzyme sphingolipid delta(4)-desaturase, which catalyzes the introduction of a double bond at the C4 position of dihydroceramide to form ceramide, a key step in sphingolipid biosynthesis. This enzyme is essential for the production of complex sphingolipids, which are critical components of cell membranes and play roles in cell signaling, differentiation, and apoptosis. Mutations in DEGS1 have been linked to a spectrum of neurological disorders, including hereditary spastic paraplegia and leukodystrophy, due to disrupted sphingolipid homeostasis in the nervous system.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (HSP) | Loss-of-function mutations in DEGS1 lead to reduced ceramide synthesis, altering sphingolipid composition in neurons and causing axonal degeneration. | ClinVar; PMID: 30661717 |
| Leukodystrophy, hypomyelinating, 18 (HLD18) | Biallelic mutations in DEGS1 cause hypomyelination and neurological deterioration, likely due to impaired oligodendrocyte function from ceramide deficiency. | OMIM #618404; PMID: 30661717 |
| Spastic paraplegia 88, autosomal recessive (SPG88) | DEGS1 mutations are associated with SPG88, characterized by progressive spasticity and weakness in lower limbs. | OMIM #618404; PMID: 30661717 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.2 | Medium |
| Liver | 12.5 | Low |
| Kidney | 10.1 | Low |
| Skin | 8.3 | Low |
| Testis | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.4 | Neuronal model |
| HepG2 (liver) | 11.2 | Hepatic expression |
| A549 (lung) | 9.8 | Low expression |
| MCF7 (breast) | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.662A>G (p.Tyr221Cys) | Missense | Rare | Loss of function; reduced enzyme activity |
| c.1A>G (p.Met1?) | Start codon loss | Rare | Loss of function; no protein synthesis |
| c.323G>A (p.Arg108His) | Missense | Rare | Loss of function; impaired catalytic activity |
| c.574C>T (p.Arg192*) | Nonsense | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most DEGS1 mutations are loss-of-function, leading to reduced or absent enzyme activity, causing ceramide deficiency and sphingolipid imbalance.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DEGS1.
Dominant Negative (DN)
No dominant-negative effects have been described; the disease is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • sphingolipid delta(4)-desaturase activity | • oxidoreductase activity |
| • ceramide biosynthetic process | • sphingolipid metabolic process |
| • endoplasmic reticulum membrane | • integral component of membrane |
Pathways
• Sphingolipid metabolism
• Ceramide biosynthesis
• Sphingosine and sphingosine-1-phosphate metabolism
Protein Summary
The DEGS1 protein is a 323-amino acid enzyme localized to the endoplasmic reticulum membrane. It belongs to the fatty acid desaturase family and contains a cytochrome b5 domain. The enzyme catalyzes the conversion of dihydroceramide to ceramide by introducing a C4 trans-double bond. This reaction is essential for the synthesis of complex sphingolipids, which are abundant in the myelin sheath and neuronal membranes. Defects in this enzyme disrupt sphingolipid homeostasis, leading to neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DEGS1 Knockout HEK293 Cell Line | EDJ-KQ1738 | Human | 8560 | Details Get a Quote |
| DEGS1 Knockout A-549 Cell Line | EDJ-KQ20238 | Human | 8560 | Details Get a Quote |
| DEGS1 Knockout HCT 116 Cell Line | EDJ-KQ21587 | Human | 8560 | Details Get a Quote |
| DEGS1 Knockout HeLa Cell Line | EDJ-KQ21588 | Human | 8560 | Details Get a Quote |
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