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 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Multiple mitochondrial dysfunctions syndrome 10MIM #620960

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Multiple mitochondrial dysfunctions syndrome 10; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in CIAO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

450 rare PASS variants

Rare truncating (LoF)

1 in 2,400

76 rare PASS variants

Rare synonymous (reference)

1 in 280

192 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CIAO1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 2,700
South Asian	~43k	1 in 150	1 in 1,200
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 6,000
European (Finnish)	~27k	1 in 280	1 in 1,400
Admixed American	~22k	1 in 110	1 in 1,300
African / African American	~21k	1 in 190	1 in 2,400
East Asian	~20k	1 in 160	1 in 3,700
Ashkenazi Jewish	~13k	1 in 2,600	1 in 1,400
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 7.? see exons ↓