DEGS1

Chr 1AR

delta 4-desaturase, sphingolipid 1

Also known as: DEGS, DEGS-1, DES1, Des-1, FADS7, HLD18, MIG15, MLD

NCBI Gene: 8560ENSG00000143753UniProt: O15121OMIM: 615843

The protein functions as a sphingolipid-delta-4-desaturase that converts sphinganine to sphingosine, catalyzing a critical step in sphingolipid biosynthesis. Biallelic mutations cause autosomal recessive leukodystrophy, hypomyelinating, 18 through disruption of sphingolipid metabolism essential for myelin formation and maintenance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.781 OMIM phenotype
Clinical Summary— DEGS1
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Gene-Disease Validity (ClinGen)
leukodystrophy, hypomyelinating, 18 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
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ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 56 VUS of 147 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.139
Z-score 2.04
OE 0.30 (0.14–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.80Z-score
OE missense 0.82 (0.72–0.95)
137 obs / 166.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.14–0.78)
0≤0.351.4
Missense OE0.82 (0.72–0.95)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 3 / 10.0Missense obs/exp: 137 / 166.2Syn Z: 0.66
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDEGS1-related leukodystrophy, hypomyelinatingLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.5464th %ile
LOF
0.3842th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic12
VUS56
Likely Benign21
Benign9
Conflicting4
41
Pathogenic
12
Likely Pathogenic
56
VUS
21
Likely Benign
9
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
35
0
41
Likely Pathogenic
6
6
0
0
12
VUS
1
47
8
0
56
Likely Benign
0
4
3
14
21
Benign
0
3
4
2
9
Conflicting
—4
Total12615016143

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DEGS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Trends in Antihypertensive Medication Use and Blood Pressure Control in Adults Aged 66-79: Results of the National Examination Surveys DEGS1 and Study on Health of Older People Gesundheit 65.
Sarganas G et al.·J Clin Hypertens (Greenwich)
2026Open Access
DEGS1-Related Hypomyelinating Leukodystrophy: Four Individuals From Same Family and Review of Literature.
Grinberg M et al.·Neurol Genet
2026Open AccessReview
Evaluating the diet in Germany with two indices focusing on healthy eating and planetary healthy eating using nationwide cross-sectional food intake data from DEGS1 (2008-2011).
Richter A et al.·Eur J Nutr
2024Open Access
Sexual and reproductive health outcomes of women who experienced violence in Germany: Analysis of the German health interview and examination survey for adults (DEGS1).
Wellmann AM et al.·PLoS One
2024Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients