CIAO1

cytosolic iron-sulfur assembly component 1, the group of WD repeat domain containing|Cytosolic iron-sulfur assembly components

Basic information

Region (hg38): 2:96266159-96274173

Previous symbols: [ "WDR39" ]

Links

ENSG00000144021 ∙ NCBI:9391 ∙ OMIM:604333 ∙ HGNC:14280 ∙ Uniprot:O76071 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple mitochondrial dysfunctions syndrome 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic	38950322

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CIAO1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CIAO1 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	1
missense		1	23			24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	23	0	1

Variants in CIAO1

This is a list of pathogenic ClinVar variants found in the CIAO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-96266418-C-G		not specified	Uncertain significance (Aug 14, 2023)
2-96266427-C-T		not specified	Uncertain significance (Oct 21, 2021)
2-96266435-A-G		not specified	Uncertain significance (Jul 22, 2024)
2-96266448-C-T		not specified	Uncertain significance (Dec 15, 2022)
2-96267331-G-T		not specified	Uncertain significance (Jun 02, 2023)
2-96267374-C-T		Multiple mitochondrial dysfunctions syndrome 10 • Neuromuscular disease	Uncertain significance (Dec 11, 2024)
2-96267378-A-G		not specified	Uncertain significance (Dec 20, 2024)
2-96267398-G-A		not specified	Uncertain significance (Jul 27, 2024)
2-96267449-A-G		not specified	Uncertain significance (Feb 18, 2025)
2-96267639-C-T			Benign (Jan 01, 2023)
2-96267685-G-A		not specified	Uncertain significance (Mar 06, 2025)
2-96267862-G-T		not specified	Uncertain significance (Oct 03, 2024)
2-96267866-G-A		not specified	Uncertain significance (Mar 11, 2025)
2-96267875-A-G		not specified	Uncertain significance (May 26, 2022)
2-96267880-C-T		not specified	Uncertain significance (Oct 07, 2024)
2-96267889-G-T		not specified	Uncertain significance (May 17, 2024)
2-96267922-G-C		not specified	Uncertain significance (Feb 27, 2023)
2-96268479-A-G		Multiple mitochondrial dysfunctions syndrome 10	Pathogenic (Sep 25, 2024)
2-96268609-T-G		not specified	Uncertain significance (Oct 12, 2024)
2-96268613-C-T		not specified	Uncertain significance (May 23, 2023)
2-96268622-C-T		not specified	Uncertain significance (Jul 30, 2024)
2-96268650-A-G		not specified	Uncertain significance (Sep 01, 2021)
2-96268652-G-A		not specified	Uncertain significance (Dec 25, 2024)
2-96269321-G-A		not specified	Uncertain significance (Mar 19, 2024)
2-96269328-A-T		Multiple mitochondrial dysfunctions syndrome 10	Pathogenic (Sep 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CIAO1	protein_coding	protein_coding	ENST00000488633	7	7218

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00125	0.991	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	153	197	0.776	0.0000111	2216
Missense in Polyphen		59	93.291	0.63243		1064
Synonymous	0.350	75	79.0	0.950	0.00000439	662
Loss of Function	2.33	8	19.0	0.422	8.99e-7	192

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins (PubMed:17937914, PubMed:23891004). As a CIA complex component, interacts specifically with CIAO2A or CIAO2B and MMS19 to assist different branches of iron-sulfur protein assembly, depending of its interactors. The complex CIAO1:CIAO2B:MMS19 binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. CIAO1:CIAO2A specifically matures ACO1 and stabilizes IREB2 (PubMed:23891004). Seems to specifically modulate the transactivation activity of WT1 (PubMed:9556563). As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (PubMed:20797633). {ECO:0000255|HAMAP- Rule:MF_03037, ECO:0000269|PubMed:17937914, ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:9556563}.

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.610
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.251
• hipred: Y
• hipred_score: 0.603
• ghis: 0.617

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ciao1

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;chromosome segregation;positive regulation of cell population proliferation;iron-sulfur cluster assembly;protein maturation by iron-sulfur cluster transfer
• Cellular component: cytoplasm;MMXD complex;CIA complex
• Molecular function: protein binding