CIAO1

Chr 2AR

cytosolic iron-sulfur assembly component 1

Also known as: CIA1, MMDS10, WDR39

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).

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Multiple mitochondrial dysfunctions syndrome 10MIM #620960
AR
0
Active trials
3
Pubs (1 yr)
37
P/LP submissions
8%
P/LP missense
0.76
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCIAO1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 78 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.001
Z-score 2.33
OE 0.42 (0.250.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.12Z-score
OE missense 0.78 (0.680.89)
153 obs / 197.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.250.76)
00.351.4
Missense OE0.78 (0.680.89)
00.61.4
Synonymous OE0.95
01.21.6
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

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

DN
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

130 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic11
VUS78
Likely Benign4
Benign1
25
Pathogenic
11
Likely Pathogenic
78
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
23
0
25
Likely Pathogenic
0
1
10
0
11
VUS
0
43
35
0
78
Likely Benign
0
2
2
0
4
Benign
0
0
0
1
1
Total048701119

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

View in ClinVar →

Protein Context — Lollipop Plot

CIAO1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC