ACAD9

Chr 3AR

acyl-CoA dehydrogenase family member 9

Also known as: MC1DN20, NPD002

NCBI Gene: 28976 ENSG00000177646 UniProt: Q9H845 OMIM: 611103

This protein functions as both a fatty acid oxidation enzyme that catalyzes the first step in mitochondrial beta-oxidation of long-chain fatty acids and as an assembly factor required for mitochondrial respiratory complex I biogenesis. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, affecting energy metabolism through dual impairment of fatty acid oxidation and oxidative phosphorylation. The gene shows low constraint to loss-of-function variants, consistent with recessive disease requiring biallelic mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the acyl-CoA dehydrogenase family. Members of this family of proteins localize to the mitochondria and catalyze the rate-limiting step in the beta-oxidation of fatty acyl-CoA. The encoded protein is specifically active toward palmitoyl-CoA and long-chain unsaturated substrates. Mutations in this gene cause acyl-CoA dehydrogenase family member type 9 deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.811 OMIM phenotype

Clinical Summary— ACAD9

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Gene-Disease Validity (ClinGen)

acyl-CoA dehydrogenase 9 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

193 unique Pathogenic / Likely Pathogenic· 265 VUS of 1209 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.37

OE 0.54 (0.37–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.18Z-score

OE missense 1.03 (0.94–1.12)

367 obs / 357.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.54 (0.37–0.81)

0≤0.351.4

Missense OE?1.03 (0.94–1.12)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 17 / 31.3Missense obs/exp: 367 / 357.5Syn Z: -0.17

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveACAD9-related acyl-CoA dehydrogenase family member type 9 deficiencyLOFAR

This gene — mechanism propensity

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

0.77top 25%

GOF

0.7029th %ile

LOF

0.2288th %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

1209 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47

Likely Pathogenic146

VUS265

Likely Benign596

Benign74

Conflicting52

Pathogenic

146

Likely Pathogenic

265

VUS

596

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	39	2	6	0	47
Likely Pathogenic	113	30	3	0	146
VUS	1	227	26	11	265
Likely Benign	2	11	294	289	596
Benign	0	1	68	5	74
Conflicting	—				52
Total	155	271	397	305	1,180

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap ACAD9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →