ACO1

aconitase 1

Basic information

Region (hg38): 9:32384603-32454769

Previous symbols: [ "IREB1" ]

Links

ENSG00000122729

∙ NCBI:48 ∙ OMIM:100880 ∙ HGNC:117 ∙ Uniprot:P21399 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACO1 gene.

not_specified (96 variants)
not_provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACO1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002197.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	4 clinvar	6
missense			95 clinvar	5 clinvar		100
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	95	7	4

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACO1	protein_coding	protein_coding	ENST00000309951	20	70150

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.83e-18	0.650	125583	0	165	125748	0.000656

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.919	454	513	0.886	0.0000282	5829
Missense in Polyphen		172	220.72	0.77927		2370
Synonymous	-0.131	192	190	1.01	0.0000109	1741
Loss of Function	1.94	35	49.8	0.703	0.00000300	538

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000672	0.000670
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000493	0.000489
Finnish	0.000462	0.000462
European (Non-Finnish)	0.000864	0.000862
Middle Eastern	0.000493	0.000489
South Asian	0.000589	0.000588
Other	0.000667	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding. {ECO:0000269|PubMed:1946430, ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:8041788}.;
Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);Warburg Effect;The oncogenic action of Succinate;The oncogenic action of Fumarate;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Iron metabolism in placenta;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Citrate cycle;TCA cycle;Transport of small molecules;TCA cycle;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Iron uptake and transport (Consensus)

Recessive Scores

pRec: 0.612

Intolerance Scores

loftool: 0.905
rvis_EVS: -1.08
rvis_percentile_EVS: 7.24

Haploinsufficiency Scores

pHI: 0.239
hipred: Y
hipred_score: 0.706
ghis: 0.551

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Aco1
Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype;

Zebrafish Information Network

Gene name: aco1
Affected structure: nucleate erythrocyte
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: tricarboxylic acid cycle;citrate metabolic process;regulation of translation;cellular iron ion homeostasis;post-embryonic development;response to iron(II) ion;intestinal absorption
Cellular component: cytoplasm;mitochondrion;endoplasmic reticulum;Golgi apparatus;cytosol;extracellular exosome
Molecular function: RNA binding;aconitate hydratase activity;protein binding;iron-responsive element binding;metal ion binding;3 iron, 4 sulfur cluster binding;4 iron, 4 sulfur cluster binding