CEP89

protein-coding

centrosomal protein 89

Gene summary

Involved in mitochondrial respiratory chain complex IV assembly and non-motile cilium assembly. Acts upstream of or within cilium assembly. Located in several cellular components, including microtubule cytoskeleton; mitochondrial intermembrane space; and non-motile cilium. Part of ciliary transition fiber. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

CCDC123

MANE transcript

NM_032816.5

Inheritance

AD, AR

ClinVar variants

U:209B:76

Top phenotype

CEP89-related disorder

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr19:32,875,925-32,971,991

External References & Databases

Ensembl (ENSG00000121289)

Transcript & Mutation Effects

hg38 • Region Span ~96.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

mitochondrial diseaseNO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *CEP89* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of July 29, 2024. The *CEP89* gene encodes centrosomal protein of 89 kDA. This protein is reported to be required for ciliogenesis, and also may play a role in mitochondrial metabolism modulating complex IV activity. This gene has been reported in association with multisystem clinical features in the medical literature (PMID: 23575228). The proband had bilateral cataracts, hearing loss, feeding problems, developmental delay, severe intellectual disability, elevated serum lactate, and cystinuria. Complex IV deficiency was noted in muscle (22% of controls). The proband had a homozygous deletion that included two genes, *SLC7A9* (associated with cystinuria) and exons 15–19 of *CEP89*. The authors postulated that the *CEP89* deletion was causative of the features not explained by cystinuria. However, this Expert Panel elected not to include this case in this curation given the size of the deletion and because other genetic etiologies were not fully excluded. Experimental evidence supporting the gene-disease relationship include expression data showing CEP89 is present in the mitochondrial intermembrane space (PMID: 23575228) and a *Drosophila melanogaster* model that showed growth defect when knocked down in the wing, lethality when knocked down in muscle, and disturbed structural integrity of the ommatidia when knocked down in the eye. Complex IV deficiency was noted in pupae from the strongest knockdown condition (PMID: 23575228). In summary, the evidence supporting the relationship between *CEP89* and primary mitochondrial disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role this gene plays in this disease. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on July 29, 2024 (SOP Version 10).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEP89 variants in ClinVar

3 Conditions Cataloged

not providedTotal: 267

not specifiedTotal: 120

CEP89-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032816.5. 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			5 clinvar	48 clinvar	5 clinvar	58
missense			181 clinvar	16 clinvar	6 clinvar	203
nonsense			12 clinvar			12
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			8 clinvar		1 clinvar	9
Total	0	0	209	64	12	285

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032816.5	RefSeq	NP_116205.3	19	MANE Select
ENST00000305768.10	Ensembl	ENSP00000306105.4	19	MANE Select
ENST00000586984.6	Ensembl	ENSP00000465141.1	13	Standard
ENST00000590597.6	Ensembl	ENSP00000466442.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Anchoring of the basal body to the plasma membrane
Cilium Assembly
Organelle biogenesis and maintenance

Biological Process

mitochondrion organization
chemical synaptic transmission
cilium assembly
ciliary basal body-plasma membrane docking
non-motile cilium assembly

Molecular Function

protein binding

Cellular Component

spindle pole
mitochondrial intermembrane space
centrosome
centriole
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305768
Coding exons: 19
Length: 92996
Individuals with no LoFs: 125314
Homozygous LoFs: 0
Heterozygous LoFs: 433
Defined: 125747
p: 0.00172

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.475	395	422	0.935	0.0000231	5105
Missense (PolyPhen)		71	79.036	0.89832		1046
Synonymous	0.196	161	164	0.981	0.00000942	1434
Loss of Function	0.364	40	42.6	0.940	0.00000213	527

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0019	0.0018	notable
Latino/Admixed American	0.0010	0.00093	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0010	0.00098	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0026	0.0025	notable
South Asian	0.0018	0.0018	notable
Other	0.0017	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for ciliogenesis. Also plays a role in mitochondrial metabolism where it may modulate complex IV activity. {ECO:0000269|PubMed:23348840, ECO:0000269|PubMed:23575228}.;
Disease: DISEASE: Note=Homozygous deletion comprising CEP89 and SLC7A9 genes has been reported in a patient with isolated complex IV deficiency, intellectual disability and multisystemic problems that include cystinuria, cataract, broad based walking pattern and deafness. {ECO:0000269|PubMed:23575228}.;

Recessive Scores

pRec: 0.0744

Intolerance Scores

RVIS EVS: 1.82
RVIS percentile EVS: 97.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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