CEP290

Chr 12AR

centrosomal protein 290

Also known as: 3H11Ag, BBS14, CT87, JBTS5, LCA10, MKS4, NPHP6, POC3

NCBI Gene: 80184ENSG00000198707UniProt: O15078

This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Bardet-Biedl syndrome 14MIM #615991
AR
Joubert syndrome 5MIM #610188
AR
Leber congenital amaurosis 10MIM #611755
Meckel syndrome 4MIM #611134
AR
Senior-Loken syndrome 6MIM #610189
AR
4428
ClinVar variants
97
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— CEP290
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 355 VUS of 4428 total submissions
💊
Clinical Trials
4 active or recruiting trials — 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.
0.98LOEUF
pLI 0.000
Z-score 1.69
OE 0.84 (0.71–0.98)
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.
0.47Z-score
OE missense 0.96 (0.91–1.01)
949 obs / 991.0 exp
Tolerant

Mild missense constraint

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.0.84 (0.71–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.91–1.01)
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.0.99
0≤1.21.6
LoF obs/exp: 104 / 124.3Missense obs/exp: 949 / 991.0Syn Z: 0.13

ClinVar Variant Classifications

4428 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic60
VUS355
Likely Benign124
Benign2
Conflicting2
37
Pathogenic
60
Likely Pathogenic
355
VUS
124
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
21
0
37
Likely Pathogenic
41
0
19
0
60
VUS
2
291
35
27
355
Likely Benign
0
5
69
50
124
Benign
0
1
1
0
2
Conflicting
—2
Total5929714577580

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP290 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CEP290-related Joubert syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Bardet-Biedl syndrome 14

MIM #615991

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 5

MIM #610188

Molecular basis of disorder known

Autosomal recessive

Leber congenital amaurosis 10

MIM #611755

Molecular basis of disorder known

Meckel syndrome 4

MIM #611134

Molecular basis of disorder known

Autosomal recessive

Senior-Loken syndrome 6

MIM #610189

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gene Editing for CEP290-Associated Retinal Degeneration.
Pierce EA et al.·N Engl J Med
2024Clinical trial
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.
Bachmann-Gagescu R et al.·J Med Genet
2015Functional
Genotype-phenotype correlates in Joubert syndrome: A review.
Gana S et al.·Am J Med Genet C Semin Med Genet
2022Review
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Georgiou M et al.·Prog Retin Eye Res
2024Review
Leber's Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations.
Huang CH et al.·Genes (Basel)
2021Review
Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy.
Xu K et al.·Br J Ophthalmol
2020Cohort
Leber Congenital Amaurosis.
Tsang SH et al.·Adv Exp Med Biol
2018Review
Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4.
Wang J et al.·Am J Ophthalmol
2023
A Description of the Yield of Genetic Reinvestigation in Patients with Inherited Retinal Dystrophies and Previous Inconclusive Genetic Testing.
Areblom M et al.·Genes (Basel)
2023Cohort
Spectrum and frequencies of extraocular features reported in CEP290-associated ciliopathy - A systematic review.
Vrabič N et al.·J Fr Ophtalmol
2024Review
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
Leber Congenital Amaurosis 10BlindnessLeber Congenital Amaurosis

A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)

ACTIVE NOT RECRUITING
NCT03913143Phase PHASE2, PHASE3ProQR TherapeuticsStarted 2019-04-04
sepofarsenSham
Leber Congenital Amaurosis 10BlindnessLeber Congenital Amaurosis

Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)

RECRUITING
NCT06891443Phase PHASE3Laboratoires TheaStarted 2025-06-04
sepofarsenPlacebo IVT
Retinitis PigmentosaLeber Congenital Amaurosis

Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis

ACTIVE NOT RECRUITING
NCT05203939Phase PHASE1, PHASE2OcugenStarted 2022-01-24
OCU400 Low DoseOCU400 Med DoseOCU400 High Dose
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools