ACO2

Chr 22ARAD

aconitase 2

Also known as: ACONM, HEL-S-284, ICRD, OCA8, OPA9

The protein is a mitochondrial enzyme that catalyzes the conversion of citrate to isocitrate in the TCA cycle, essential for cellular energy production. Mutations cause infantile cerebellar-retinal degeneration and optic atrophy 9, affecting the central nervous system and visual system with early onset manifestations. The gene follows both autosomal recessive and autosomal dominant inheritance patterns and shows moderate constraint against loss-of-function variants (LOEUF 0.417).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.422 OMIM phenotypes
Clinical SummaryACO2
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ADStrong

Strong evidence — appropriate for clinical testing

3 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.208
Z-score 4.33
OE 0.24 (0.140.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.92Z-score
OE missense 0.63 (0.570.69)
304 obs / 485.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.140.42)
00.351.4
Missense OE0.63 (0.570.69)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 9 / 37.7Missense obs/exp: 304 / 485.0Syn Z: 0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveACO2-related infantile cerebellar-retinal degenerationLOFAR
strongACO2-related optic atrophyOTHERAR

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

DN
0.6455th %ile
GOF
0.5660th %ile
LOF
0.4628th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACO2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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