ACADS

Chr 12AR

acyl-CoA dehydrogenase short chain

Also known as: ACAD3, SCAD

NCBI Gene: 35ENSG00000122971UniProt: P16219

This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in this gene have been associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Alternative splicing results in two variants which encode different isoforms. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

Acyl-CoA dehydrogenase, short-chain, deficiency ofMIM #201470
AR
529
ClinVar variants
67
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ACADS
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 116 VUS of 529 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.95LOEUF
pLI 0.000
Z-score 1.74
OE 0.59 (0.38–0.95)
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.
0.58Z-score
OE missense 0.90 (0.81–1.00)
239 obs / 265.8 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.0.59 (0.38–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.00)
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.0.96
0≤1.21.6
LoF obs/exp: 12 / 20.5Missense obs/exp: 239 / 265.8Syn Z: 0.32

ClinVar Variant Classifications

529 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic38
VUS116
Likely Benign116
Benign16
Conflicting8
29
Pathogenic
38
Likely Pathogenic
116
VUS
116
Likely Benign
16
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
4
18
0
29
Likely Pathogenic
16
14
8
0
38
VUS
0
95
21
0
116
Likely Benign
0
2
52
62
116
Benign
0
1
13
2
16
Conflicting
—8
Total2311611264323

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

View in ClinVar →

Protein Context — Lollipop Plot

ACADS · protein map & ClinVar variants

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

Gene2Phenotype Curations

ACADS-related short chain acyl-CoA dehydrogenase deficiency

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Acyl-CoA dehydrogenase, short-chain, deficiency of

MIM #201470

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Diverse and unselected adults with clinically relevant ACADS variants lack evidence of metabolic disease.
Breilyn MS et al.·Mol Genet Metab
2023
Novel and Recurrent ACADS Mutations and Clinical Manifestations Observed in Korean Patients with Short-chain Acyl-coenzyme a Dehydrogenase Deficiency.
Kim YM et al.·Ann Clin Lab Sci
2016Cohort
An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia.
Lisyová J et al.·BMC Med Genet
2018
Dynamic modelling of an ACADS genotype in fatty acid oxidation - Application of cellular models for the analysis of common genetic variants.
Matejka K et al.·PLoS One
2019Functional
COADREADx: A comprehensive algorithmic dissection of colorectal cancer unravels salient biomarkers and actionable insights into its discrete progression.
Palaniappan A et al.·PeerJ
2024
Integrated Analysis of Expression and Prognostic Values of Acyl-CoA Dehydrogenase short-chain in Colorectal Cancer.
Wu Q et al.·Int J Med Sci
2021
Analysis of genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine.
Wu D et al.·Zhejiang Da Xue Xue Bao Yi Xue Ban
2023
The minor C-allele of the rs2014355 variant in ACADS gene is associated with exercise-induced increase in HDL cholesterol levels in Taiwanese adults.
Yang TP et al.·Medicine (Baltimore)
2021
Variants in the ethylmalonyl-CoA decarboxylase (ECHDC1) gene: a novel player in ethylmalonic aciduria?
Fogh S et al.·J Inherit Metab Dis
2021
The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level.
Pedersen CB et al.·Hum Genet
2008Cohort
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

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools