ACO1

aconitase 1

Basic information

Region (hg38): 9:32384602-32454769

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.

• Inborn genetic diseases (33 variants)
• not provided (5 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	4	5
missense			33			33
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	33	1	4

Variants in ACO1

This is a list of pathogenic ClinVar variants found in the ACO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-32407261-G-A		not specified	Uncertain significance (May 08, 2023)
9-32407263-C-T		not specified	Uncertain significance (Oct 14, 2023)
9-32407387-A-G		not specified	Uncertain significance (Jun 24, 2022)
9-32407407-C-T		not specified	Uncertain significance (Jan 30, 2024)
9-32408593-C-G		not specified	Uncertain significance (Jan 19, 2024)
9-32418356-G-A		not specified	Uncertain significance (Nov 15, 2023)
9-32418362-T-C		not specified	Uncertain significance (Jul 27, 2022)
9-32418446-C-T		not specified	Uncertain significance (Feb 28, 2023)
9-32418453-C-G		not specified	Uncertain significance (Nov 30, 2022)
9-32418457-G-A		not specified	Uncertain significance (Dec 17, 2021)
9-32419135-C-T			Benign (Jun 30, 2017)
9-32419143-T-G		not specified	Uncertain significance (Mar 13, 2023)
9-32419166-A-T		not specified	Uncertain significance (Nov 27, 2023)
9-32420862-C-T		not specified	Uncertain significance (Jan 16, 2024)
9-32420863-G-T		not specified	Uncertain significance (Mar 06, 2023)
9-32420895-T-C		not specified	Uncertain significance (Aug 15, 2023)
9-32420914-C-T		not specified	Uncertain significance (Sep 26, 2022)
9-32420922-T-C		not specified	Uncertain significance (Oct 04, 2022)
9-32421011-G-A			Likely benign (Apr 24, 2018)
9-32423322-G-A		not specified	Uncertain significance (Dec 18, 2023)
9-32423336-T-A		not specified	Uncertain significance (Sep 16, 2021)
9-32423363-G-T		not specified	Uncertain significance (Oct 02, 2023)
9-32423403-A-G		not specified	Uncertain significance (Aug 08, 2022)
9-32425838-C-G		not specified	Uncertain significance (Dec 07, 2021)
9-32425853-T-C		not specified	Uncertain significance (Mar 15, 2023)

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