CIAO3

protein-coding

cytosolic iron-sulfur assembly component 3, the group of Cytosolic iron-sulfur assembly components

Gene summary

Predicted to enable 4 iron, 4 sulfur cluster binding activity and metal ion binding activity. Involved in several processes, including intracellular oxygen homeostasis; iron-sulfur cluster assembly; and response to hypoxia. Part of cytosolic [4Fe-4S] assembly targeting complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

NARFL

MANE transcript

NM_022493.3

Inheritance

ClinVar variants

U:96B:12

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr16:729,760-741,329

External References & Databases

Ensembl (ENSG00000103245)

Transcript & Mutation Effects

hg38 • Region Span ~11.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pulmonary arteriovenous malformationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009930

Submitter: Illumina

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CIAO3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 7

High myopiaTotal: 1

Pulmonary arteriovenous malformationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022493.3. 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	3
missense			85 clinvar	10 clinvar	1 clinvar	96
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	96	10	2	108

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022493.3	RefSeq	NP_071938.1	11	MANE Select
ENST00000251588.7	Ensembl	ENSP00000251588.2	11	MANE Select
NM_001304799.2	RefSeq	NP_001291728.1	8	Standard
ENST00000540986.5	Ensembl	ENSP00000444008.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
narfl	Danio rerio	Structure: subintestinal vein Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

narfl

Danio rerio

Structure: subintestinal vein

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to hypoxia
hematopoietic progenitor cell differentiation
regulation of gene expression
iron-sulfur cluster assembly
oxygen homeostasis

Molecular Function

protein binding
metal ion binding
4 iron, 4 sulfur cluster binding

Cellular Component

CIA complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251588
Coding exons: 11
Length: 11577
Individuals with no LoFs: 125665
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125714
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.226	286	297	0.963	0.0000190	3062
Missense (PolyPhen)		92	112.91	0.81481		1217
Synonymous	-1.85	159	132	1.20	0.00000970	943
Loss of Function	1.32	17	24.0	0.709	0.00000137	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00044	0.00044	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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. Seems to negatively regulate the level of HIF1A expression, although this effect could be indirect. {ECO:0000269|PubMed:16956324, ECO:0000269|PubMed:18270200}.;

Recessive Scores

pRec: 0.184

Intolerance Scores

RVIS EVS: -0.11
RVIS percentile EVS: 45.61

Essentials

Essential (gene trap): E