CEP120

protein-coding

centrosomal protein 120

Gene summary

This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Previous symbols:

CCDC100

MANE transcript

NM_001375405.1

Inheritance

ClinVar variants

P:53U:269B:145

Top phenotype

Joubert syndrome 31; Short-rib thoracic dysplasia 13 with or without polydactyly

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr5:123,344,890-123,423,592

External References & Databases

Ensembl (ENSG00000168944)

Transcript & Mutation Effects

hg38 • Region Span ~78.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ciliopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: G2P

ciliopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: ClinGen

The *CEP120* gene is located on chromosome 5 at q23.2 and encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome, which is required for centriole elongation from a procentriole. It expresses in a variety of tissues and organs, including the kidney. Multiple disease entities have been reported in association with this gene. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, there was no evidence of differences in their molecular mechanism and/or inheritance pattern. Therefore, the following disease entities have been lumped into one disease entity. *CEP120* was first reported in relation to autosomal recessive ciliopathies in 2015 (Shaheen et al., PMID: 25361962). Clinical presentations include developmental delay, hypotonia, abnormal breathing and eye movements, truncal ataxia, auditory pathway abnormalities, molar tooth sign with cerebellar vermis hypoplasia, ventriculomegaly, and callosal hypoplasia, craniofacial dysmorphism, skeletal anomalies, and renal involvement such as pyelocalyceal dilation, hydronephrosis, or cystic kidneys. The mechanism of pathogenicity is reported to be loss of function. Fifteen variants (missense, nonsense, and frameshift) have been reported in 14 probands in 6 publications (PMIDs: 25361962, 37547106, 27208211, 38050708, 37272176, 34930662) and are included in this curation. The maximum genetic evidence was reached, considering case-level data, and functional data. This gene-disease relationship is also supported by non-patient cells, and non-human models. *CEP120* deficiency induces ciliopathies in mice and zebrafish (PMIDs: 37982452, 38177914, 29847808, 25361962). A total of 5/6 points for experimental evidence was reached. In summary, there is definitive evidence supporting the relationship between *CEP120* and ciliopathy-*CEP120*. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on the meeting date June 25th, 2025 (SOP Version 11).

short-rib thoracic dysplasia 13 with or without polydactylySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014577

Submitter: Labcorp Genetics (formerly Invitae)

Jeune syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018770

Submitter: Orphanet

Joubert syndrome 31STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033310

Submitter: Labcorp Genetics (formerly Invitae)

Joubert syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018772

Submitter: Orphanet

Joubert syndrome with ocular defectSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016364

Submitter: Orphanet

Clinical Genomic Database (CGD)

Joubert syndrome 31; Short-rib thoracic dysplasia 13 with or without polydactylyAR

Manifestation: Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25361962; 27208211

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEP120 variants in ClinVar

7 Conditions Cataloged

Short-rib thoracic dysplasia 13 with or without polydactylyTotal: 403

not providedTotal: 164

Inborn genetic diseasesTotal: 156

not specifiedTotal: 120

CEP120-related disorderTotal: 53

Joubert syndrome 31Total: 19

Chuvash polycythemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001375405.1. 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	110 clinvar		112
missense	3 clinvar	3 clinvar	260 clinvar	34 clinvar	1 clinvar	301
nonsense	8 clinvar	13 clinvar	1 clinvar			22
start loss			2 clinvar			2
frameshift	5 clinvar	9 clinvar	2 clinvar			16
splice donor/acceptor (+/-2bp)		12 clinvar	2 clinvar			14
Total	16	37	269	144	1	467

Highest pathogenic variant AF is 0.00002360835

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001375405.1	RefSeq	NP_001362334.1	20	MANE Select
ENST00000306467.10	Ensembl	ENSP00000303058.6	20	MANE Select
NM_001166226.2	RefSeq	NP_001159698.1	19	Standard
NM_001375406.1	RefSeq	NP_001362335.1	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cep120	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cep120

Danio rerio

Structure: otolith

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

centrosome cycle
positive regulation of centrosome duplication
cerebral cortex development
neurogenesis
interkinetic nuclear migration

Molecular Function

protein binding
protein C-terminus binding

Cellular Component

centrosome
centriole

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306467
Coding exons: 20
Length: 78708
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125748
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.233	525	510	1.03	0.0000265	6432
Missense (PolyPhen)		135	144.54	0.93401		1848
Synonymous	-0.228	180	176	1.02	0.00000887	1836
Loss of Function	2.78	32	54.1	0.592	0.00000270	680

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00042	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0011	0.00098	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00028	0.00025	rare
South Asian	0.00014	0.00013	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis (By similarity). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4- dependent manner (PubMed:27185865). {ECO:0000250|UniProtKB:Q7TSG1, ECO:0000269|PubMed:27185865}.;
Disease: DISEASE: Short-rib thoracic dysplasia 13 with or without polydactyly (SRTD13) [MIM:616300]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:25361962}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 31 (JBTS31) [MIM:617761]: A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS31 inheritance is autosomal recessive. {ECO:0000269|PubMed:27208211}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.954
RVIS EVS: 0.01
RVIS percentile EVS: 54.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.135

Gene Damage Prediction

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