DECR1

Chr 8

2,4-dienoyl-CoA reductase 1

Also known as: DECR, NADPH, SDR18C1

DECR1 encodes an auxiliary enzyme that catalyzes the NADPH-dependent reduction of 2,4-dienoyl-CoA to trans-3-enoyl-CoA during mitochondrial beta-oxidation of unsaturated fatty acids. Mutations cause hyperlysinemia with saccharopinuria, an autosomal recessive disorder affecting amino acid metabolism. This gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

Summary from RefSeq, UniProt
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Primary Disease Associations & Inheritance

UniProt2,4-dienoyl-CoA reductase deficiency
0
Active trials
19
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
1.68
LOEUF
DN
Mechanism· predicted
Clinical SummaryDECR1
🧬
Gene-Disease Validity (ClinGen)
progressive encephalopathy with leukodystrophy due to DECR deficiency · UDNo Known Disease Relationship

No known disease relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 49 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.68LOEUF
pLI 0.000
Z-score -0.58
OE 1.15 (0.801.68)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.03Z-score
OE missense 0.99 (0.881.12)
180 obs / 181.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.15 (0.801.68)
00.351.4
Missense OE0.99 (0.881.12)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 19 / 16.5Missense obs/exp: 180 / 181.2Syn Z: 0.56
DN
0.7036th %ile
GOF
0.4973th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

117 submitted variants in ClinVar

Classification Summary

Pathogenic33
VUS49
Likely Benign9
Benign4
33
Pathogenic
49
VUS
9
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
0
0
0
VUS
0
40
9
0
49
Likely Benign
0
6
0
3
9
Benign
0
0
2
2
4
Total04644595

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

View in ClinVar →

Protein Context — Lollipop Plot

DECR1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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