ACO1

Chr 9

aconitase 1

Also known as: ACONS, HEL60, IREB1, IREBP, IREBP1, IRP1

The encoded protein functions as both a cytosolic aconitase that catalyzes the conversion of citrate to isocitrate in the TCA cycle and as an iron-responsive element-binding protein that regulates cellular iron homeostasis by controlling translation and stability of iron-related mRNAs. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and movement abnormalities. The phenotypes reflect disruption of both mitochondrial energy metabolism and cellular iron regulation affecting primarily the nervous system.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.93
Clinical SummaryACO1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.94
OE 0.70 (0.540.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.92Z-score
OE missense 0.89 (0.820.96)
454 obs / 512.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.540.93)
00.351.4
Missense OE0.89 (0.820.96)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 35 / 49.8Missense obs/exp: 454 / 512.5Syn Z: -0.13
DN
0.6356th %ile
GOF
0.5856th %ile
LOF
0.3939th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACO1 · 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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