ACOD1

Summary

ACOD1 (aconitate decarboxylase 1, HGNC:33904) is a protein-coding gene on chromosome 13q22.3, encoding Cis-aconitate decarboxylase (A6NK06). Cis-aconitate decarboxylase that catalyzes production of itaconate and is involved in the inhibition of the inflammatory response.

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.

Source: NCBI Gene 730249 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 28 total — 17 pathogenic
• MANE Select transcript: NM_001258406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33904
Approved symbol	ACOD1
Name	aconitate decarboxylase 1
Location	13q22.3
Locus type	gene with protein product
Status	Approved
Aliases	CAD
Ensembl gene	ENSG00000102794
Ensembl biotype	protein_coding
OMIM	615275
Entrez	730249

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377462

RefSeq mRNA: 1 — MANE Select: NM_001258406 NM_001258406

CCDS: CCDS58299

Canonical transcript exons

ENST00000377462 — 5 exons

Exon	Start	End
ENSE00000802451	76953600	76953689
ENSE00000802452	76955319	76955524
ENSE00001474008	76957010	76958638
ENSE00001474009	76952489	76952650
ENSE00001474010	76948511	76948570

Expression profiles

Bgee: expression breadth broad, 40 present calls, max score 83.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 31.5129 / max 6761.0505, expressed in 135 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135460	31.4939	135
135484	0.0190	10

Top tissues by expression

233 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	83.02	gold quality
left ventricle myocardium	UBERON:0006566	82.96	gold quality
kidney epithelium	UBERON:0004819	80.84	gold quality
epithelial cell of pancreas	CL:0000083	79.90	gold quality
parotid gland	UBERON:0001831	76.91	gold quality
myocardium	UBERON:0002349	75.69	gold quality
upper arm skin	UBERON:0004263	75.51	gold quality
ileal mucosa	UBERON:0000331	72.28	silver quality
endothelial cell	CL:0000115	68.64	gold quality
nasal cavity epithelium	UBERON:0005384	65.26	silver quality
epithelium of nasopharynx	UBERON:0001951	63.12	gold quality
deltoid	UBERON:0001476	62.72	gold quality
layer of synovial tissue	UBERON:0007616	58.79	gold quality
quadriceps femoris	UBERON:0001377	57.87	gold quality
superficial temporal artery	UBERON:0001614	56.83	gold quality
gingival epithelium	UBERON:0001949	56.39	gold quality
vastus lateralis	UBERON:0001379	55.67	gold quality
saphenous vein	UBERON:0007318	55.64	gold quality
epithelium of mammary gland	UBERON:0003244	54.70	gold quality
urethra	UBERON:0000057	54.54	gold quality
mammary duct	UBERON:0001765	54.45	gold quality
pericardium	UBERON:0002407	54.40	gold quality
upper leg skin	UBERON:0004262	54.29	silver quality
thymus	UBERON:0002370	54.11	gold quality
dorsal root ganglion	UBERON:0000044	54.10	gold quality
trigeminal ganglion	UBERON:0001675	54.08	gold quality
nipple	UBERON:0002030	54.07	gold quality
synovial joint	UBERON:0002217	54.07	gold quality
cardia of stomach	UBERON:0001162	54.00	gold quality
inferior vagus X ganglion	UBERON:0005363	53.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting ACOD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-219A-1-3P	98.91	67.87	639

Literature-anchored findings (GeneRIF, showing 23)

• Results indicated that the IRG1 gene is differentially expressed in human fetal PBMCs and LPS-stimulated adult PBMCs. (PMID:21424586)
• inducible IRG1 promotes endotoxin tolerance by increasing A20 expression through ROS, indicating a new molecular mechanism regulating hypoinflammation of sepsis and endotoxin tolerance. (PMID:23609450)
• IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production (PMID:23610393)
• Irg1 gene encodes an enzyme synthesizing itaconic acid from the TCA cycle intermediate cisaconitate. Furthermore, our data also show that IRG1 mediated itaconic acid production contributes to the antimicrobial activity of macrophages. (PMID:23610393)
• Findings revealed that IRG1 is a candidate oncogene that is amplified in glioma and is involved in novel mechanisms that influence glioma pathogenesis. (PMID:25216059)
• IRF1 is a transcriptional regulator of IRG1 in human macrophages. (PMID:26872335)
• IRG1/CAD associates with mitochondria in human macrophages under inflammatory conditions such as LPS and/or IFNg. (PMID:26872335)
• Taken together, the results show that IRG1 is expressed by human monocytes, macrophages and dendritic cells and that it is rapidly induced in both human and murine macrophages under inflammatory conditions such as LPS, TNFa and IFNg. (PMID:26872335)
• We identified IRF1 as a transcriptional regulator of IRG1 expression in both human and mouse macrophages under inflammatory conditions. (PMID:26872335)
• Respiratory syncytial virus infection induced IRG1 expression in human A549 cells and in the lung tissues of respiratory syncytial virus -infected mice and respiratory syncytial virus infection or IRG1 overexpression promoted reactive oxygen species production. (PMID:27252532)
• findings suggest that polymorphisms in the immunoresponsive gene 1 (IRG1) gene are associated with the immune response to hepatitis B vaccination; observed that IRG1 inhibited the HBV life cycle and that IRG1 rs17385627 allele ‘A’ was more effective than rs17385627 allele ‘T’ at eliminating HBV in HepG2.2.15 cell (PMID:28004399)
• In conclusion, we found that IRG1 promoted MHC I level in macrophages membrane via ROS-STAT1/3-TAP1 pathway. Besides, IRG1 could activate the pentose phosphate pathway to promote production of ROS depending on NADPH oxidases. (PMID:28477473)
• identified 8 active-site residues critical for CAD function and rare naturally occurring human mutations in the active site that abolished CAD activity, as well as a variant (Asn152Ser) that increased CAD activity and is common (allele frequency 20%) in African ethnicity (PMID:31548418)
• Immune-Responsive Gene 1/Itaconate Activates Nuclear Factor Erythroid 2-Related Factor 2 in Hepatocytes to Protect Against Liver Ischemia-Reperfusion Injury. (PMID:31997373)
• Role of IRG1 in Regulating Pro-inflammatory and Pro-labor Mediators in Human Myometrium. (PMID:32046417)
• Itaconate prevents abdominal aortic aneurysm formation through inhibiting inflammation via activation of Nrf2. (PMID:32574955)
• The Tumor Necrosis Factor Alpha and Interleukin 6 Auto-paracrine Signaling Loop Controls Mycobacterium avium Infection via Induction of IRF1/IRG1 in Human Primary Macrophages. (PMID:34607464)
• Aconitate decarboxylase 1 is a mediator of polymicrobial sepsis. (PMID:36001682)
• Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever. (PMID:36479617)
• [Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants]. (PMID:37096266)
• Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy. (PMID:37115931)
• Amino acid positions near the active site determine the reduced activity of human ACOD1 compared to murine ACOD1. (PMID:37365251)
• Acod1 expression in cancer cells promotes immune evasion through the generation of inhibitory peptides. (PMID:38520689)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	acod1	ENSDARG00000069844
mus_musculus	Acod1	ENSMUSG00000022126
rattus_norvegicus	Acod1	ENSRNOG00000009919

Protein

Protein identifiers

Cis-aconitate decarboxylase — A6NK06 (reviewed: A6NK06)

Alternative names: Aconitate decarboxylase, Aconitate decarboxylase 1, Cis-aconitic acid decarboxylase, Immune-responsive gene 1 protein

All UniProt accessions (1): A6NK06

UniProt curated annotations — full annotation on UniProt →

Function. Cis-aconitate decarboxylase that catalyzes production of itaconate and is involved in the inhibition of the inflammatory response. Acts as a negative regulator of the Toll-like receptors (TLRs)-mediated inflammatory innate response by stimulating the tumor necrosis factor alpha-induced protein TNFAIP3 expression via reactive oxygen species (ROS) in LPS-tolerized macrophages. Involved in antimicrobial response of innate immune cells; ACOD1-mediated itaconic acid production contributes to the antimicrobial activity of macrophages by generating itaconate, leading to alkylation of proteins, such as TFEB. Involved in antiviral response following infection by flavivirus in neurons: ACOD1-mediated itaconate production inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes. Plays a role in the embryo implantation.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion.

Tissue specificity. Expressed in LPS-tolerized macrophages (at protein level). Expressed in peripheral blood mononuclear cells (PBMCs), microglia and macrophage cells.

Induction. Up-regulated after lipopolysaccharide (LPS) stimulation. Up-regulated in LPS-tolerized macrophage by LPS. Up-regulated in peripheral blood mononuclear cells (PBMC) of patient after acute sepsis.

Similarity. Belongs to the PrpD family.

RefSeq proteins (1): NP_001245335* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005656	MmgE_PrpD	Family
IPR036148	MmgE/PrpD_sf	Homologous_superfamily
IPR042183	MmgE/PrpD_sf_1	Homologous_superfamily
IPR042188	MmgE/PrpD_sf_2	Homologous_superfamily
IPR045336	MmgE_PrpD_N	Domain
IPR045337	MmgE_PrpD_C	Domain

Pfam: PF03972, PF19305

Enzyme classification (BRENDA):

• EC 4.1.1.6 — cis-aconitate decarboxylase (BRENDA: 7 organisms, 9 substrates, 9 inhibitors, 12 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CIS-ACONITATE	0.34–9	9

Catalyzed reactions (Rhea), 1 shown:

• cis-aconitate + H(+) = itaconate + CO2 (RHEA:15253)

UniProt features (60 total): helix 28, strand 9, sequence variant 8, mutagenesis site 8, turn 4, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6R6U	X-RAY DIFFRACTION	1.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NK06-F1	95.45	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (8):

Position	Phenotype
93	abolished cis-aconitate decarboxylase activity.
97	strongly reduced cis-aconitate decarboxylase activity.
103	abolished cis-aconitate decarboxylase activity.
159	abolished cis-aconitate decarboxylase activity.
207	abolished cis-aconitate decarboxylase activity.
272	abolished cis-aconitate decarboxylase activity.
277	abolished cis-aconitate decarboxylase activity.
318	abolished cis-aconitate decarboxylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 605 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_TOLERANCE_INDUCTION, GOBP_RESPONSE_TO_COCAINE, GOBP_RESPONSE_TO_AMINE, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (23): positive regulation of antimicrobial humoral response (GO:0002760), defense response (GO:0006952), inflammatory response (GO:0006954), embryo implantation (GO:0007566), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of type I interferon production (GO:0032480), negative regulation of toll-like receptor 2 signaling pathway (GO:0034136), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), cellular response to interferon-beta (GO:0035458), negative regulation of innate immune response (GO:0045824), negative regulation of inflammatory response (GO:0050728), defense response to virus (GO:0051607), cellular response to molecule of bacterial origin (GO:0071219), cellular response to lipopolysaccharide (GO:0071222), cellular response to cocaine (GO:0071314), cellular response to type II interferon (GO:0071346), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), cellular response to progesterone stimulus (GO:0071393), tolerance induction to lipopolysaccharide (GO:0072573), positive regulation of reactive oxygen species metabolic process (GO:2000379), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (3): protein homodimerization activity (GO:0042803), aconitate decarboxylase activity (GO:0047613), lyase activity (GO:0016829)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to cytokine stimulus	4
defense response	2
negative regulation of immune system process	2
negative regulation of signal transduction	2
negative regulation of defense response	2
negative regulation of response to external stimulus	2
cellular response to oxygen-containing compound	2
regulation of antimicrobial humoral response	1
positive regulation of response to biotic stimulus	1
positive regulation of humoral immune response	1
antimicrobial humoral response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
response to stress	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
toll-like receptor 2 signaling pathway	1
regulation of toll-like receptor 2 signaling pathway	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
response to interferon-beta	1
negative regulation of response to biotic stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
inflammatory response	1
regulation of inflammatory response	1
response to virus	1
response to molecule of bacterial origin	1
cellular response to biotic stimulus	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
response to cocaine	1
cellular response to alkaloid	1
response to type II interferon	1

Protein interactions and networks

STRING

1829 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACOD1	GOT2	P00505	924
ACOD1	IFIT1	P09914	683
ACOD1	ACO2	Q99798	608
ACOD1	CXCL10	P02778	576
ACOD1	ACO1	P21399	574
ACOD1	IRF7	Q92985	561
ACOD1	TLR2	O60603	526
ACOD1	TLR3	O15455	500
ACOD1	TLR5	O60602	499
ACOD1	TLR7	Q9NYK1	493
ACOD1	IL1B	P01584	488
ACOD1	STAT3	P40763	483
ACOD1	TIRAP	P58753	477
ACOD1	IDH1	O75874	453
ACOD1	NFKBIZ	Q9BYH8	452

IntAct

0 interactions, top by confidence:

BioGRID (3): IRG1 (Affinity Capture-MS), IRG1 (Cross-Linking-MS (XL-MS)), IRG1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A067MTM1, A0A0A0RM07, A0A2I2F2N6, A0A3G9H9I5, A0A3G9K3K9, A2XL32, A6NK06, A8WTJ7, B3IUN8, B8AY75, M1WCF5, O13698, O13702, O48929, O49187, O74419, O74542, O81122, O82436, O94265, P49333, P54956, P54987, P9WES1, P9WES2, P9WEY4, Q01N44, Q04554, Q06490, Q0C8L3, Q0DKM0, Q0JFH7, Q10089, Q28XT3, Q2SHX7, Q2TXG0, Q4H4F8, Q53RH0, Q7Q547, Q8F8T4

Diamond homologs: A6NK06, P54987

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

28 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1341055	GRCh37/hg19 13q21.1-31.2(chr13:59574760-89410027)x1	Pathogenic
145515	GRCh38/hg38 13q21.32-31.2(chr13:66320998-87855429)x1	Pathogenic
145617	GRCh38/hg38 13q21.2-31.1(chr13:60536344-84553188)x1	Pathogenic
149289	GRCh38/hg38 13q13.1-31.1(chr13:32531486-86757044)x3	Pathogenic
149578	GRCh38/hg38 13q21.33-31.1(chr13:72681540-79638468)x1	Pathogenic
1527778	GRCh37/hg19 13q21.2-31.1(chr13:61686543-83302092)	Pathogenic
1527784	GRCh37/hg19 13q22.2-31.2(chr13:75574661-87784831)	Pathogenic
152961	GRCh38/hg38 13q21.31-31.1(chr13:63713365-79638415)x1	Pathogenic
153559	GRCh38/hg38 13q22.2-31.1(chr13:76530209-78531570)x1	Pathogenic
253533	GRCh37/hg19 13q21.33-31.2(chr13:72013791-88021559)x1	Pathogenic
3063284	GRCh37/hg19 13q21.1-31.3(chr13:56450978-93582180)x1	Pathogenic
33174	GRCh38/hg38 13q12.3-31.3(chr13:31363472-90575292)x3	Pathogenic
394747	GRCh37/hg19 13q22.3-31.1(chr13:77455170-81099829)x1	Pathogenic
4076066	GRCh37/hg19 13q14.3-31.2(chr13:54206989-88417670)x1	Pathogenic
564079	GRCh37/hg19 13q22.2-31.3(chr13:76942604-90660121)x1	Pathogenic
57227	GRCh38/hg38 13q14.12-31.3(chr13:44967523-92738168)x1	Pathogenic
59868	GRCh38/hg38 13q12.3-31.1(chr13:30318913-83610426)x3	Pathogenic

SpliceAI

841 predictions. Top by Δscore:

Variant	Effect	Δscore
13:76953690:G:GG	donor_gain	1.0000
13:76953695:G:GT	donor_gain	1.0000
13:76949426:C:G	donor_gain	0.9900
13:76949433:GCT:G	donor_gain	0.9900
13:76949434:C:G	donor_gain	0.9900
13:76950615:G:GT	donor_gain	0.9900
13:76952487:A:G	acceptor_gain	0.9900
13:76952488:G:GG	acceptor_gain	0.9900
13:76953686:GGCT:G	donor_gain	0.9900
13:76953687:GCT:G	donor_gain	0.9900
13:76953687:GCTG:G	donor_gain	0.9900
13:76953723:A:G	donor_gain	0.9900
13:76955314:TACAG:T	acceptor_loss	0.9900
13:76955315:ACAG:A	acceptor_loss	0.9900
13:76955316:C:G	acceptor_gain	0.9900
13:76955316:CA:C	acceptor_loss	0.9900
13:76955317:A:AG	acceptor_gain	0.9900
13:76955317:AGA:A	acceptor_loss	0.9900
13:76955318:G:GG	acceptor_gain	0.9900
13:76955318:GA:G	acceptor_gain	0.9900
13:76955318:GAT:G	acceptor_gain	0.9900
13:76955318:GATT:G	acceptor_gain	0.9900
13:76955318:GATTC:G	acceptor_gain	0.9900
13:76955465:TATTG:T	donor_gain	0.9900
13:76955466:ATTGA:A	donor_gain	0.9900
13:76955522:GAG:G	donor_gain	0.9900
13:76957009:GATTC:G	acceptor_gain	0.9900
13:76948566:TCAAG:T	donor_loss	0.9800
13:76948567:CAAGG:C	donor_loss	0.9800
13:76948568:AAGGT:A	donor_loss	0.9800

AlphaMissense

3155 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:76957536:T:C	S333P	0.996
13:76957191:G:T	G218W	0.995
13:76957355:G:C	K272N	0.995
13:76957355:G:T	K272N	0.995
13:76953630:T:A	W69R	0.991
13:76953630:T:C	W69R	0.991
13:76957051:C:A	A171D	0.991
13:76952564:A:C	S30R	0.990
13:76952566:C:A	S30R	0.990
13:76952566:C:G	S30R	0.990
13:76957708:T:A	V390D	0.990
13:76957044:A:C	S169R	0.989
13:76957046:T:A	S169R	0.989
13:76957046:T:G	S169R	0.989
13:76957174:G:A	G212D	0.988
13:76957531:G:C	R331P	0.988
13:76952592:G:A	G39D	0.987
13:76957054:C:A	A172D	0.987
13:76957354:A:C	K272T	0.987
13:76957554:T:C	C339R	0.987
13:76957593:T:C	F352L	0.987
13:76957595:C:A	F352L	0.987
13:76957595:C:G	F352L	0.987
13:76957759:G:A	G407E	0.987
13:76952583:A:T	D36V	0.986
13:76957200:G:C	A221P	0.985
13:76957354:A:T	K272M	0.985
13:76952598:G:A	G41E	0.984
13:76957098:G:C	A187P	0.984
13:76957556:T:G	C339W	0.984

dbSNP variants (sampled 300 via entrez): RS1000196345 (13:76949381 T>C), RS1000264365 (13:76956233 C>T), RS1000314429 (13:76947934 T>A,C), RS1000346905 (13:76948290 A>G), RS1000496931 (13:76955004 G>C), RS1000540933 (13:76954751 C>T), RS1000556484 (13:76954843 G>T), RS1000939900 (13:76948021 G>A,T), RS1002498117 (13:76952120 G>A), RS1002549127 (13:76951668 A>G), RS1002564330 (13:76955456 C>T), RS1002885587 (13:76950118 G>A), RS1003438113 (13:76956625 G>A), RS1003453423 (13:76956644 C>A,T), RS1004214777 (13:76947489 G>A)

Disease associations

OMIM: gene MIM:615275 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002543_1	Hearing function	7.000000e-08
GCST002682_13	Tourette’s syndrome or obsessive-compulsive disorder	1.000000e-06
GCST012304_3	Major depressive disorder	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Itaconate biosynthesis

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
TL8-506	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1CM	Ubigene THP-1 ACOD1 KO	Cancer cell line	Male
CVCL_ST04	HAP1 ACOD1 (-) 1	Cancer cell line	Male
CVCL_ST05	HAP1 ACOD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.