ACOD1
Chr 13aconitate decarboxylase 1
Also known as: CAD, IRG1
The ACOD1 protein functions as a cis-aconitate decarboxylase that produces itaconate to regulate inflammatory and antimicrobial responses in immune cells. Mutations in ACOD1 cause immunodeficiency with severe reduction in NK and T cells, B cell dysfunction, susceptibility to viral infections, and colitis, following autosomal recessive inheritance. The gene shows low constraint to loss-of-function variants, consistent with the recessive inheritance pattern of associated immunodeficiency disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
83 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 72 |
Likely Pathogenic | — | — | — | — | 0 |
VUS | — | — | — | — | 5 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 4 |
| Total | — | 82 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ACOD1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools