CIAO1

protein-coding

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

Gene summary

Involved in iron-sulfur cluster assembly and protein maturation. Located in cytoplasm. Part of MMXD complex and cytosolic [4Fe-4S] assembly targeting complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

WDR39

MANE transcript

NM_004804.3

Inheritance

ClinVar variants

P:4U:51B:3

Top phenotype

Multiple mitochondrial dysfunctions syndrome 10

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr2:96,266,159-96,274,173

External References & Databases

Ensembl (ENSG00000144021)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multiple mitochondrial dysfunctions syndrome 10LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0975806

Submitter: Ambry Genetics

multiple mitochondrial dysfunctions syndrome 10LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0975806

Submitter: G2P

Clinical Genomic Database (CGD)

Multiple mitochondrial dysfunctions syndrome 10AR

Manifestation: Biochemical; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 38950322

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CIAO1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 43

Multiple mitochondrial dysfunctions syndrome 10Total: 6

not providedTotal: 4

Neuromuscular diseaseTotal: 3

CIAO1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004804.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	1 clinvar	4
missense	2 clinvar	2 clinvar	43 clinvar	1 clinvar		48
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	2	2	51	2	1	58

Highest pathogenic variant AF is 0.0016398845

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004804.3	RefSeq	NP_004795.1	7	MANE Select
ENST00000488633.2	Ensembl	ENSP00000418287.1	7	MANE Select
ENST00000883965.1	Ensembl	ENSP00000554024.1	7	Standard
ENST00000883965.2	Ensembl	ENSP00000554024.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

protein binding

Cellular Component

cytoplasm
MMXD complex
CIA complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000488633
Coding exons: 7
Length: 7218
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	153	197	0.776	0.0000111	2216
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

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