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Aliases for ACO2 Gene

Aliases for ACO2 Gene

  • Aconitase 2 2 3 5
  • Aconitate Hydratase, Mitochondrial 2 3
  • Aconitase 2, Mitochondrial 2 3
  • Mitochondrial Aconitase 2 3
  • Citrate Hydro-Lyase 3 4
  • EC 4 56
  • Epididymis Secretory Sperm Binding Protein Li 284 3
  • Aconitase 4
  • HEL-S-284 3
  • EC 4.2.1 56
  • ACONM 3
  • ICRD 3
  • OCA8 3
  • OPA9 3

External Ids for ACO2 Gene

Previous GeneCards Identifiers for ACO2 Gene

  • GC22P038479
  • GC22P040108
  • GC22P040189
  • GC22P041865
  • GC22P024830

Summaries for ACO2 Gene

Entrez Gene Summary for ACO2 Gene

  • The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

GeneCards Summary for ACO2 Gene

ACO2 (Aconitase 2) is a Protein Coding gene. Diseases associated with ACO2 include Infantile Cerebellar-Retinal Degeneration and Optic Atrophy 9. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Pyruvate metabolism and Citric Acid (TCA) cycle. Gene Ontology (GO) annotations related to this gene include iron ion binding and aconitate hydratase activity. An important paralog of this gene is ACO1.

UniProtKB/Swiss-Prot for ACO2 Gene

  • Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.

Additional gene information for ACO2 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ACO2 Gene

Genomics for ACO2 Gene

GeneHancer (GH) Regulatory Elements for ACO2 Gene

Promoters and enhancers for ACO2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH22I041467 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE dbSUPER 550.8 +1.7 1705 7 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766 PHF5A ACO2 POLR3H MEI1 TOB2 EP300 NAGA CSDC2 L3MBTL2 FAM109B
GH22I041444 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 12.7 -22.4 -22409 5.9 MLX ZFP64 FEZF1 DMAP1 YBX1 IRF4 YY1 SLC30A9 ZNF213 ZNF143 TOB2 LOC105373043 L3MBTL2 ZC3H7B PHF5A EP300 SLC25A17 POLR3H NDUFA6-AS1 XRCC6
GH22I041397 Enhancer 1.1 ENCODE dbSUPER 11.3 -71.7 -71693 0.2 ELF3 FOXA2 ARID4B THRB ZNF48 RAD21 RARA YY1 CREM THAP11 PIR38134 PIR55540 PIR50015 PIR58640 TEF PHF5A ACO2 CSDC2 GC22P041361
GH22I041443 Enhancer 0.8 FANTOM5 ENCODE dbSUPER 11.8 -25.7 -25716 0.4 KLF7 MLLT1 GC22P041443 PHF5A ACO2 CYP2D6 TOB2 LOC105373043
GH22I041497 Enhancer 0.7 ENCODE dbSUPER 12.2 +30.3 30309 4.2 ZNF121 CTCF ZNF654 ZNF143 SMC3 HNF4A RAD21 PIR44656 PHF5A ACO2 CSDC2 ENSG00000227370 L3MBTL2 POLR3H GC22M042674
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around ACO2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ACO2 gene promoter:

Genomic Locations for ACO2 Gene

Genomic Locations for ACO2 Gene
59,865 bases
Plus strand

Genomic View for ACO2 Gene

Genes around ACO2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ACO2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ACO2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ACO2 Gene

Proteins for ACO2 Gene

  • Protein details for ACO2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Aconitate hydratase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • O75809
    • Q5JZ41
    • Q6FHX0
    • Q8TAQ6

    Protein attributes for ACO2 Gene

    780 amino acids
    Molecular mass:
    85425 Da
    Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
    Quaternary structure:
    • Monomer.

neXtProt entry for ACO2 Gene

Selected DME Specific Peptides for ACO2 Gene


Post-translational modifications for ACO2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ACO2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for ACO2 Gene

Gene Families for ACO2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the aconitase/IPM isomerase family.
  • Belongs to the aconitase/IPM isomerase family.
genes like me logo Genes that share domains with ACO2: view

Function for ACO2 Gene

Molecular function for ACO2 Gene

GENATLAS Biochemistry:
aconitase 2,iron sulfur protein,catalyzing the mitochondrial,second step of citric acid cycle,ubiquitously expressed,including multiple isoforms
UniProtKB/Swiss-Prot CatalyticActivity:
Citrate = isocitrate.
UniProtKB/Swiss-Prot Function:
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.

Enzyme Numbers (IUBMB) for ACO2 Gene

Phenotypes From GWAS Catalog for ACO2 Gene

Gene Ontology (GO) - Molecular Function for ACO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003994 aconitate hydratase activity EXP 1052766
GO:0005506 iron ion binding IDA 9630632
GO:0016829 lyase activity IEA --
GO:0046872 metal ion binding IEA --
GO:0051536 iron-sulfur cluster binding IEA --
genes like me logo Genes that share ontologies with ACO2: view
genes like me logo Genes that share phenotypes with ACO2: view

Human Phenotype Ontology for ACO2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for ACO2

Clone Products

  • Addgene plasmids for ACO2

No data available for Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for ACO2 Gene

Localization for ACO2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ACO2 Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ACO2 gene
Compartment Confidence
mitochondrion 5
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ACO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion HDA,TAS 20833797
GO:0005759 mitochondrial matrix TAS --
GO:0043209 myelin sheath IEA --
genes like me logo Genes that share ontologies with ACO2: view

Pathways & Interactions for ACO2 Gene

genes like me logo Genes that share pathways with ACO2: view

UniProtKB/Swiss-Prot Q99798-ACON_HUMAN

  • Pathway: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 2/2.

Gene Ontology (GO) - Biological Process for ACO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001889 liver development IEA --
GO:0006091 generation of precursor metabolites and energy TAS 9630632
GO:0006099 tricarboxylic acid cycle TAS,IDA --
GO:0006101 citrate metabolic process IDA,IEA 9630632
GO:0006102 isocitrate metabolic process IEA --
genes like me logo Genes that share ontologies with ACO2: view

No data available for SIGNOR curated interactions for ACO2 Gene

Drugs & Compounds for ACO2 Gene

(8) Drugs for ACO2 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Citric Acid Approved, Vet_approved Nutra Agonist, Activator 1243
Isocitric acid Experimental Pharma Target 0
4-Hydroxy-Aconitate Ion Experimental Pharma Target 0
Aconitate Ion Experimental Pharma Target 0

(7) Additional Compounds for ACO2 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
1,2,3-Propanetricarboxylic acid
  • 1,2,3-Tripropanetricarboxylic acid
  • 3-Carboxyglutaric acid
  • beta-Carboxyglutaric acid
  • Carballylic acid
  • Propane 1,2,3-tricarboxylic acid
cis-Aconitic acid
  • (1Z)-1-Propene-1,2,3-tricarboxylate
  • (1Z)-1-Propene-1,2,3-tricarboxylic acid
  • (Z)-1-Propene-1,2,3-tricarboxylate
  • (Z)-1-Propene-1,2,3-tricarboxylic acid
  • (Z)-Aconitate
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
Homocitric acid
  • (R)-2-Hydroxy-1,2,4-butanetricarboxylate
  • (R)-2-Hydroxy-1,2,4-butanetricarboxylic acid
  • 2-Hydroxybutane-1,2,4-tricarboxylate
  • 3-Hydroxy-3-carboxyadipate
  • 3-Hydroxy-3-carboxyadipic acid
genes like me logo Genes that share compounds with ACO2: view

Transcripts for ACO2 Gene

Unigene Clusters for ACO2 Gene

Aconitase 2, mitochondrial:
Representative Sequences:

Clone Products

  • Addgene plasmids for ACO2

Alternative Splicing Database (ASD) splice patterns (SP) for ACO2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11
SP1: - - -
SP2: -
SP3: - -
SP5: - - - - - - - - - - - -
SP6: -

Relevant External Links for ACO2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for ACO2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ACO2 Gene

mRNA differential expression in normal tissues according to GTEx for ACO2 Gene

This gene is overexpressed in Heart - Left Ventricle (x6.4) and Muscle - Skeletal (x5.3).

Protein differential expression in normal tissues from HIPED for ACO2 Gene

This gene is overexpressed in Heart (10.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for ACO2 Gene

Protein tissue co-expression partners for ACO2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ACO2 Gene:


SOURCE GeneReport for Unigene cluster for ACO2 Gene:


Evidence on tissue expression from TISSUES for ACO2 Gene

  • Nervous system(4.9)
  • Liver(4.6)
  • Muscle(4.6)
  • Skin(4)
  • Lung(3.6)
  • Heart(3.5)
  • Blood(2.9)
  • Stomach(2.6)
  • Eye(2.4)
  • Intestine(2.4)
  • Kidney(2.3)
  • Adrenal gland(2.2)
  • Gall bladder(2.1)
  • Pancreas(2.1)
  • Thyroid gland(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ACO2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
  • nervous
  • skeletal muscle
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • eye
  • head
  • mouth
  • tongue
  • arm
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • toe
  • upper limb
  • peripheral nerve
  • peripheral nervous system
genes like me logo Genes that share expression patterns with ACO2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA Expression by UniProt/SwissProt for ACO2 Gene

Orthologs for ACO2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ACO2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ACO2 34
  • 96 (a)
(Monodelphis domestica)
Mammalia ACO2 34
  • 94 (a)
(Canis familiaris)
Mammalia ACO2 33 34
  • 91.45 (n)
(Bos Taurus)
Mammalia ACO2 33 34
  • 91.37 (n)
(Ornithorhynchus anatinus)
Mammalia ACO2 34
  • 91 (a)
(Mus musculus)
Mammalia Aco2 16 34 33
  • 89.87 (n)
(Rattus norvegicus)
Mammalia Aco2 33
  • 89.74 (n)
(Gallus gallus)
Aves ACO2 33 34
  • 80.98 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 90 (a)
-- 34
  • 83 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia aco2 33
  • 76.64 (n)
Str.823 33
(Danio rerio)
Actinopterygii aco2 33 34
  • 74.79 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007852 33
  • 70.42 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4706 35 34
  • 70 (a)
Acon 33 34
  • 69.92 (n)
(Caenorhabditis elegans)
Secernentea aco-2 35 33 34
  • 66.98 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ADL032W 33
  • 64.57 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ACO1 33 34
  • 62.19 (n)
ACO2 36
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C17314g 33
  • 60.52 (n)
(Hordeum vulgare)
Liliopsida Hv.13082 33
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3336 34
  • 71 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU02366 33
  • 66.01 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPAC24C9.06c 33
  • 61.35 (n)
Species where no ortholog for ACO2 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ACO2 Gene

Gene Tree for ACO2 (if available)
Gene Tree for ACO2 (if available)

Paralogs for ACO2 Gene

Paralogs for ACO2 Gene

(1) SIMAP similar genes for ACO2 Gene using alignment to 3 proteins: Pseudogenes for ACO2 Gene

genes like me logo Genes that share paralogs with ACO2: view

Variants for ACO2 Gene

Sequence variations from dbSNP and Humsavar for ACO2 Gene

SNP ID Clin Chr 22 pos Variation AA Info Type
rs1057518831 uncertain-significance, Brain atrophy, Central hypoventilation, Global developmental delay, Neurodegeneration, Progressive microcephaly 41,523,856(+) A/C coding_sequence_variant, missense_variant
rs1057518832 uncertain-significance, Brain atrophy, Central hypoventilation, Global developmental delay, Neurodegeneration, Progressive microcephaly 41,499,765(+) C/T 5_prime_UTR_variant, coding_sequence_variant, synonymous_variant
rs1057518833 uncertain-significance, Brain atrophy, Central hypoventilation, Global developmental delay, Neurodegeneration, Progressive microcephaly 41,499,764(+) C/T 5_prime_UTR_variant, coding_sequence_variant, synonymous_variant
rs141772938 pathogenic, uncertain-significance, Optic atrophy 9, not specified, Optic atrophy 9 (OPA9) [MIM:616289] 41,507,837(+) C/G coding_sequence_variant, missense_variant
rs203319 likely-benign, benign, not specified 41,518,589(+) C/G/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ACO2 Gene

Variant ID Type Subtype PubMed ID
esv3647798 CNV loss 21293372
esv3647799 CNV gain 21293372
nsv516925 CNV loss 19592680
nsv524585 CNV loss 19592680
nsv834208 CNV loss 17160897

Variation tolerance for ACO2 Gene

Residual Variation Intolerance Score: 8.61% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.53; 29.63% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ACO2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ACO2 Gene

Disorders for ACO2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for ACO2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
infantile cerebellar-retinal degeneration
  • icrd
optic atrophy 9
  • opa9
autosomal recessive isolated optic atrophy
  • autosomal recessive nonsyndromic optic atrophy
retinal degeneration
  • degeneration of retina
- elite association - COSMIC cancer census association via MalaCards
Search ACO2 in MalaCards View complete list of genes associated with diseases


  • Infantile cerebellar-retinal degeneration (ICRD) [MIM:614559]: A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration. {ECO:0000269 PubMed:22405087, ECO:0000269 PubMed:25351951}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Optic atrophy 9 (OPA9) [MIM:616289]: A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. {ECO:0000269 PubMed:25351951}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ACO2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ACO2: view

No data available for Genatlas for ACO2 Gene

Publications for ACO2 Gene

  1. The DNA sequence of human chromosome 22. (PMID: 10591208) Dunham I … O'Brien KP (Nature 1999) 2 3 4 58
  2. Characterization of the human mitochondrial aconitase gene (ACO2). (PMID: 9630632) Mirel DB … Wilhelmsen KC (Gene 1998) 3 4 22 58
  3. Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy. (PMID: 25351951) Metodiev MD … Besmond C (Journal of medical genetics 2014) 3 4 58
  4. Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. (PMID: 22405087) Spiegel R … Elpeleg O (American journal of human genetics 2012) 3 4 58
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 44 58

Products for ACO2 Gene

  • Addgene plasmids for ACO2

Sources for ACO2 Gene

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