CIAO1

Chr 2AR

cytosolic iron-sulfur assembly component 1

Also known as: CIA1, MMDS10, WDR39

NCBI Gene: 9391 ENSG00000144021 UniProt: O76071 OMIM: 604333

CIAO1 encodes a key component of the cytosolic iron-sulfur protein assembly complex that mediates incorporation of iron-sulfur clusters into cytosolic and nuclear proteins. Mutations cause multiple mitochondrial dysfunctions syndrome 10, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variants (pLI 0.001, LOEUF 0.76).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in protein maturation. Located in cytoplasm. Part of MMXD complex and cytosolic [4Fe-4S] assembly targeting complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.761 OMIM phenotype

Clinical Summary— CIAO1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 45 VUS of 64 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.001

Z-score 2.33

OE 0.42 (0.25–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.12Z-score

OE missense 0.78 (0.68–0.89)

153 obs / 197.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.25–0.76)

0≤0.351.4

Missense OE?0.78 (0.68–0.89)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 8 / 19.0Missense obs/exp: 153 / 197.1Syn Z: 0.35

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedCIAO1-related neuromuscular disorder with intellectual disabilityLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6646th %ile

GOF

0.5071th %ile

LOF

0.3551th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic1

VUS45

Likely Benign2

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	1	0	3
Likely Pathogenic	0	1	0	0	1
VUS	1	43	1	0	45
Likely Benign	0	2	0	0	2
Benign	0	0	0	1	1
Conflicting	—				1
Total	1	48	2	1	53

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 68) ClinVar copy-number / structural variants overlap CIAO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →