DEGS1

Chr 1

delta 4-desaturase, sphingolipid 1

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

NCBI Gene: 8560 ENSG00000143753 UniProt: O15121

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.78

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

20 unique Pathogenic / Likely Pathogenic· 52 VUS of 109 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.30 (0.14–0.78)

0≤0.351.4

Missense OE?0.82 (0.72–0.95)

0≤0.61.4

Synonymous OE?0.89

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

This gene — mechanism propensity

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

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

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic12

VUS52

Likely Benign21

Benign9

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	2	0	8
Likely Pathogenic	6	6	0	0	12
VUS	1	49	2	0	52
Likely Benign	0	4	3	14	21
Benign	0	3	4	2	9
Conflicting	—				4
Total	12	63	11	16	106

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap DEGS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →