DEGS1

Chr 1AR

delta 4-desaturase, sphingolipid 1

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

NCBI Gene: 8560ENSG00000143753UniProt: O15121

This gene encodes a member of the membrane fatty acid desaturase family which is responsible for inserting double bonds into specific positions in fatty acids. This protein contains three His-containing consensus motifs that are characteristic of a group of membrane fatty acid desaturases. It is predicted to be a multiple membrane-spanning protein localized to the endoplasmic reticulum. Overexpression of this gene inhibited biosynthesis of the EGF receptor, suggesting a possible role of a fatty acid desaturase in regulating biosynthetic processing of the EGF receptor. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 18MIM #618404
AR
143
ClinVar variants
53
Pathogenic / LP
0.14
pLI score
1
Active trials
Clinical Summary— DEGS1
🧬
Gene-Disease Validity (ClinGen)
leukodystrophy, hypomyelinating, 18 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 56 VUS of 143 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.139
Z-score 2.04
OE 0.30 (0.14–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.80Z-score
OE missense 0.82 (0.72–0.95)
137 obs / 166.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.14–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.72–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 3 / 10.0Missense obs/exp: 137 / 166.2Syn Z: 0.66

ClinVar Variant Classifications

143 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
3
1
37
0
41
Likely Pathogenic
3
6
3
0
12
VUS
0
47
9
0
56
Likely Benign
0
4
3
14
21
Benign
0
3
4
2
9
Conflicting
—4
Total6615616143

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.

Gene2Phenotype Curations

DEGS1-related leukodystrophy, hypomyelinating

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukodystrophy, hypomyelinating, 18

MIM #618404

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Burden of disease in myasthenia gravis: taking the patient's perspective.
Lehnerer S et al.·J Neurol
2022
DEGS1 -related leukodystrophy: a clinical report and review of literature.
Wong MST et al.·Clin Dysmorphol
2023Review
Recent genetic advances in early-onset dystonia.
Steel D et al.·Curr Opin Neurol
2020Review
DEGS1 variant causes neurological disorder.
Dolgin V et al.·Eur J Hum Genet
2019
Deletion Testing of the DEGS1 Gene Should Be Part of the Diagnostic Pipeline for Hypomyelinating Leukodystrophy (HLD18).
Zanobio M et al.·Hum Mutat
2025Case report
The pathophysiological role of dihydroceramide desaturase in the nervous system.
Tzou FY et al.·Prog Lipid Res
2023Review
Exome sequencing in four families with neurodevelopmental disorders: genotype-phenotype correlation and identification of novel disease-causing variants in VPS13B and RELN.
Afridi TUK et al.·Mol Genet Genomics
2024
DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans.
Karsai G et al.·J Clin Invest
2019
Identification and characterization of mitochondrial autophagy-related genes in osteosarcoma and predicting clinical prognosis.
Zhang H et al.·Sci Rep
2025
The atypical sphingolipid SPB 18:1(14Z);O2 is a biomarker for DEGS1 related hypomyelinating leukodystrophy.
Hülsmeier AJ et al.·J Lipid Res
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
PrediabetesOverweight , Obesity

Exercise, Chronotype, and Prediabetes

NOT YET RECRUITING
NCT07389005Phase NAGerman Diabetes CenterStarted 2026-02
Timing of exerciseTiming of exerciseControl

External Resources

Links to major genomics databases and tools