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DEGS1
delta 4-desaturase, sphingolipid 1
The DEGS1 gene provides instructions for an enzyme involved in the synthesis of sphingolipids, which are crucial components of cell membranes and signalling molecules. DEGS1 encodes delta 4-desaturase, sphingolipid 1, an enzyme vital for converting dihydroceramide to ceramide.
DEGS1 is located on the long (q) arm of chromosome 1, at band 1q42.11. Arm ratio per GRCh38 - banding schematic.
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Overview
The DEGS1 gene, formally known as delta 4-desaturase, sphingolipid 1, is essential for metabolic processes within the body. It provides instructions for producing an enzyme that plays a critical role in the synthesis of sphingolipids.
Sphingolipids are a diverse class of lipids that are fundamental components of cell membranes and act as potent signalling molecules. Dysregulation of DEGS1-mediated pathways can therefore impact a broad range of cellular activities.
What the gene does
The DEGS1 gene product, delta 4-desaturase, sphingolipid 1, is an enzyme primarily responsible for the desaturation of dihydroceramide into ceramide. This enzymatic step introduces a double bond at the C4-C5 position of the sphingoid backbone.
Ceramide is a critical precursor for the synthesis of more complex sphingolipids, including sphingomyelin and glycosphingolipids, which are integral to cell membrane structure and function. This enzyme's activity is therefore crucial for maintaining the delicate balance of sphingolipid metabolism, which in turn influences cell growth, differentiation, and programmed cell death.
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Chromosome location
The DEGS1 gene is situated on chromosome 1, specifically at position 1q42.11. This location indicates its precise address within the human genome. Detailed information regarding the number of exons for the DEGS1 gene is available through genomic databases.
Protein structure
The DEGS1 protein has a length of 323 amino acids. Its structural integrity and enzymatic function rely on specific conserved regions. Key functional motifs include Histidine box-1, located between amino acids 89-93, Histidine box-2, found at amino acids 128-132, and Histidine box-3, situated from amino acids 259-263. These histidine-rich boxes are characteristic of desaturase enzymes and are essential for their catalytic activity.
Key variants
Genetic variations, or variants, within the DEGS1 gene can alter the function of the encoded enzyme. These alterations may reduce or abolish the enzyme's ability to desaturate dihydroceramide, leading to a disruption in sphingolipid synthesis. The specific clinical impact of a variant depends on its nature and location within the gene, which can range from benign to pathogenic.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.320G>A | p.Trp107Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 18 |
c.337A>G | p.Asn113Asp | Pathogenic/Likely pathogenic | ★★☆☆ | DEGS1-related Hypomyelinating Leukodystrophy |
c.517C>T | p.Arg173Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 18 |
c.764A>G | p.Asn255Ser | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 18 |
c.852_855del | p.Tyr283_Tyr284insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 18 |
c.22G>T | p.Glu8Ter | Pathogenic | ★☆☆☆ | not provided |
c.252dup | p.Thr85fs | Pathogenic | ★☆☆☆ | not provided |
c.49C>T | p.Gln17Ter | Pathogenic | ★☆☆☆ | not provided |
c.825+4_825+5delinsTT | - | Pathogenic | ★☆☆☆ | not provided |
c.604del | p.Tyr202fs | Pathogenic | - | Leukodystrophy, hypomyelinating, 18 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variability in the DEGS1 gene's function has been implicated in a spectrum of inherited conditions, predominantly impacting neurological development and function. These conditions often arise from disrupted sphingolipid metabolism, which is critical for the proper formation and maintenance of the nervous system. The inheritance pattern of such conditions can vary.
No disease links recorded for this gene in our reference set.
UK clinical status
In the UK, the DEGS1 gene is recognised within several NHS Genomic Medicine Service national panels for inherited conditions. It is listed as 'green' on the DDG2P panel, the Early onset or syndromic epilepsy panel (R59), the Hereditary neuropathy panel, the Intellectual disability panel (R29), and the White matter disorders and cerebral calcification - narrow panel. This indicates that variants in DEGS1 are considered to have a strong association with the conditions covered by these panels, supporting its inclusion in diagnostic testing pathways.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the DEGS1 gene?
The DEGS1 gene provides instructions for an enzyme called delta 4-desaturase, sphingolipid 1. This enzyme is crucial for converting dihydroceramide into ceramide, a foundational step in the synthesis of various important sphingolipids.
Why are sphingolipids important for health?
Sphingolipids are vital components of cell membranes, contributing to their structure and fluidity. They also act as important signalling molecules involved in processes such as cell growth, differentiation, and communication within the body.
How can changes in the DEGS1 gene affect individuals?
Variants in the DEGS1 gene can lead to reduced or altered function of the DEGS1 enzyme. This disruption in sphingolipid metabolism may contribute to various inherited conditions, particularly those affecting neurological development and function.