ACOD1

Chr 13

aconitate decarboxylase 1

Also known as: CAD, IRG1

NCBI Gene: 730249 ENSG00000102794 UniProt: A6NK06

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.

ResearchSummary from RefSeq, UniProt

Enables aconitate decarboxylase activity and protein homodimerization activity. Involved in defense response; positive regulation of antimicrobial humoral response; and tolerance induction to lipopolysaccharide. Predicted to be active in mitochondrion. Biomarker of esophageal carcinoma and head and neck squamous cell carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

121

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.98

OE 0.72 (0.44–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.58Z-score

OE missense 0.72 (0.64–0.82)

186 obs / 257.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.44–1.22)

0≤0.351.4

Missense OE?0.72 (0.64–0.82)

0≤0.61.4

Synonymous OE?0.62

0≤1.21.6

LoF obs/exp: 10 / 13.9Missense obs/exp: 186 / 257.1Syn Z: 3.03

Background carrier burden — how many people carry a rare variant somewhere in ACOD1?

gnomAD v4 · ~699k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

572 rare PASS variants

Rare truncating (LoF)

1 in 2,600

64 rare PASS variants

Rare synonymous (reference)

1 in 190

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACOD1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~540k	1 in 150	1 in 3,600
South Asian	~40k	1 in 64	1 in 3,000
Remaining (unassigned)	~29k	1 in 90	1 in 3,600
European (Finnish)	~24k	1 in 520	≈ 1 in 24,000
African / African American	~21k	1 in 55	1 in 820
East Asian	~18k	1 in 78	1 in 620
Admixed American	~18k	1 in 80	1 in 1,300
Ashkenazi Jewish	~13k	1 in 660	none seen
Middle Eastern	~2,852	1 in 82	1 in 570

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 5.? see exons ↓