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…

Primary Disease Associations & Inheritance

UniProtLeukodystrophy, hypomyelinating, 18

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · leukodystrophy, hypomyelinating, 18 · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in DEGS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

386 rare PASS variants

Rare truncating (LoF)

1 in 4,400

56 rare PASS variants

Rare synonymous (reference)

1 in 640

149 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DEGS1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 4,400
South Asian	~43k	1 in 160	1 in 4,000
Remaining (unassigned)	~30k	1 in 160	1 in 980
European (Finnish)	~27k	1 in 1,400	≈ 1 in 12,000
Admixed American	~22k	1 in 170	1 in 3,700
African / African American	~21k	1 in 240	1 in 2,200
East Asian	~20k	1 in 180	1 in 3,800
Ashkenazi Jewish	~13k	1 in 440	none seen
Middle Eastern	~2,884	1 in 150	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓