CEP120

Chr 5AR

centrosomal protein 120

Also known as: CCDC100, JBTS31, SRTD13

NCBI Gene: 153241ENSG00000168944UniProt: Q8N960

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]

Primary Disease Associations & Inheritance

Joubert syndrome 31MIM #617761
AR
Short-rib thoracic dysplasia 13 with or without polydactylyMIM #616300
AR
581
ClinVar variants
34
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CEP120
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 229 VUS of 581 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 2.78
OE 0.59 (0.45–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.23Z-score
OE missense 1.03 (0.96–1.11)
525 obs / 510.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.45–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.96–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 32 / 54.1Missense obs/exp: 525 / 510.2Syn Z: -0.23

ClinVar Variant Classifications

581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic15
VUS229
Likely Benign241
Benign63
Conflicting14
19
Pathogenic
15
Likely Pathogenic
229
VUS
241
Likely Benign
63
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
15
0
19
Likely Pathogenic
12
0
3
0
15
VUS
1
215
13
0
229
Likely Benign
0
9
135
97
241
Benign
0
3
58
2
63
Conflicting
—14
Total1722722499581

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP120 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CEP120-related ciliopathy syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Joubert syndrome 31

MIM #617761

Molecular basis of disorder known

Autosomal recessive

Short-rib thoracic dysplasia 13 with or without polydactyly

MIM #616300

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CEP120
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development.
Powell L et al.·BMC Dev Biol
2020
Meiosis interrupted: the genetics of female infertility via meiotic failure.
Biswas L et al.·Reproduction
2021Review
Predicting Infertility: How Genetic Variants in Oocyte Spindle Genes Affect Egg Quality.
Biswas L et al.·Adv Anat Embryol Cell Biol
2024Review
Update of genetic variants in CEP120 and CC2D2A-With an emphasis on genotype-phenotype correlations, tissue specific transcripts and exploring mutation specific exon skipping therapies.
Barroso-Gil M et al.·Mol Genet Genomic Med
2021
Exome sequencing links CEP120 mutation to maternally derived aneuploid conception risk.
Tyc KM et al.·Hum Reprod
2020
[Clinical and genetic analyses of Joubert syndrome in children].
Zhang GY et al.·Zhongguo Dang Dai Er Ke Za Zhi
2023
A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies.
Shaheen R et al.·Hum Mol Genet
2015
Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes.
Roosing S et al.·J Med Genet
2016
Exome Study of Single Nucleotide Variations in Patients with Syndromic and Non-Syndromic Autism Reveals Potential Candidate Genes for Diagnostics and Novel Single Nucleotide Variants.
Belenska-Todorova L et al.·Cells
2025Cohort
Pituitary stalk interruption syndrome is characterized by genetic heterogeneity.
Brauner R et al.·PLoS One
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
PSC

Colangioids to Define the Genetic Factors Involved in Atypical Primary Sclerosing Cholangitis

ACTIVE NOT RECRUITING
NCT06865924Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2024-12-01
Use of assembloids as in vitro models to test new pharmacological approaches

External Resources

Links to major genomics databases and tools