CEP290

centrosomal protein 290, the group of MKS complex

Basic information

Region (hg38): 12:88049016-88142099

Links

ENSG00000198707 ∙ NCBI:80184 ∙ OMIM:610142 ∙ HGNC:29021 ∙ Uniprot:O15078 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 5 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 14 (Moderate), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
• Senior-Loken syndrome (Supportive), mode of inheritance: AR
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 14 (Strong), mode of inheritance: AR
• Joubert syndrome 5 (Strong), mode of inheritance: AR
• Leber congenital amaurosis 10 (Strong), mode of inheritance: AR
• CEP290-related ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 14	AR	Endocrine	Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	16909394; 16682973; 16682970; 17564974; 17564967; 17554762; 17617513; 17898177; 17705300; 18327255; 20301537; 20690115; 20805370; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP290 gene.

• Bardet-Biedl syndrome 14 (108 variants)
• Familial aplasia of the vermis;Nephronophthisis;Meckel-Gruber syndrome (103 variants)
• Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis (70 variants)
• not provided (68 variants)
• Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis (65 variants)
• Nephronophthisis;Meckel-Gruber syndrome;Familial aplasia of the vermis (64 variants)
• Leber congenital amaurosis (54 variants)
• Joubert syndrome 5 (41 variants)
• Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis (39 variants)
• Nephronophthisis;Familial aplasia of the vermis;Meckel-Gruber syndrome (30 variants)
• CEP290-related disorder (20 variants)
• Retinal dystrophy (19 variants)
• Meckel syndrome, type 4 (18 variants)
• Leber congenital amaurosis 10 (17 variants)
• Retinitis pigmentosa (5 variants)
• Inborn genetic diseases (5 variants)
• Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5 (4 variants)
• CEP290-related ciliopathy (4 variants)
• Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14 (3 variants)
• Meckel syndrome, type 4;Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10 (3 variants)
• Meckel syndrome, type 4;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14 (3 variants)
• Joubert syndrome 1 (3 variants)
• Meckel syndrome, type 4;Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (3 variants)
• not specified (2 variants)
• Senior-Loken syndrome 6;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Joubert syndrome 5 (2 variants)
• Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Bardet-Biedl syndrome 14 (2 variants)
• Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14 (2 variants)
• Nephronophthisis (2 variants)
• Bardet-Biedl syndrome 14;Joubert syndrome 5;Meckel syndrome, type 4;Senior-Loken syndrome 6;Leber congenital amaurosis 10 (2 variants)
• Leber congenital amaurosis 10;Senior-Loken syndrome 6;Bardet-Biedl syndrome 14;Joubert syndrome 5;Meckel syndrome, type 4 (2 variants)
• Bardet-Biedl syndrome 14;Meckel syndrome, type 4;Joubert syndrome 5;Leber congenital amaurosis 10;Senior-Loken syndrome 6 (2 variants)
• Familial aplasia of the vermis (2 variants)
• Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5 (2 variants)
• Joubert syndrome 5;Bardet-Biedl syndrome 14 (1 variants)
• Night blindness (1 variants)
• Joubert syndrome 5;Meckel syndrome, type 4;Leber congenital amaurosis 10;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6 (1 variants)
• See cases (1 variants)
• Central hypotonia;Nystagmus;Molar tooth sign on MRI (1 variants)
• Intellectual disability (1 variants)
• Senior-Loken syndrome 6;Joubert syndrome 5;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10 (1 variants)
• Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
• Occipital encephalocele;Cystic renal dysplasia (1 variants)
• Abnormality of prenatal development or birth (1 variants)
• Bardet-Biedl syndrome 14;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6 (1 variants)
• Blindness;Global developmental delay (1 variants)
• Joubert syndrome 5;Senior-Loken syndrome 6;Meckel syndrome, type 4;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10 (1 variants)
• Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
• Occipital encephalocele (1 variants)
• Kidney disorder (1 variants)
• Spastic ataxia (1 variants)
• Abnormality of the nervous system (1 variants)
• Senior-Loken syndrome 6 (1 variants)
• Senior-Loken syndrome 6;Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4 (1 variants)
• Leber congenital amaurosis 10;Meckel syndrome, type 4;Joubert syndrome 5;Bardet-Biedl syndrome 14;Senior-Loken syndrome 6 (1 variants)
• Joubert syndrome 5;Bardet-Biedl syndrome 14;Leber congenital amaurosis 10;Meckel syndrome, type 4;Senior-Loken syndrome 6 (1 variants)
• Senior-Loken syndrome 6;Joubert syndrome 5;Leber congenital amaurosis 10;Meckel syndrome, type 4;Bardet-Biedl syndrome 14 (1 variants)
• 6 conditions (1 variants)
• Encephalocele;Polycystic kidney disease;Severe hydrocephalus (1 variants)
• Blindness (1 variants)
• Severe hydrocephalus;Polycystic kidney disease;Encephalocele (1 variants)
• Meckel-Gruber syndrome (1 variants)
• Meckel syndrome, type 4;Leber congenital amaurosis 10;Senior-Loken syndrome 6;Joubert syndrome 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP290 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	806	1	818
missense	1	9	945	12	5	972
nonsense	169	88				257
start loss	2	2				4
frameshift	202	156	4			362
inframe indel			29			29
splice donor/acceptor (+/-2bp)	30	103	2	1		136
splice region	3	5	41	182	12	243
non coding	2	2	20	552	85	661
Total	406	360	1011	1371	91

Highest pathogenic variant AF is 0.0000923

Variants in CEP290

This is a list of pathogenic ClinVar variants found in the CEP290 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-88049033-A-G		Bardet-Biedl syndrome 14 • Meckel syndrome, type 4 • Joubert syndrome 5 • Senior-Loken syndrome 6 • Leber congenital amaurosis 10	Uncertain significance (Jan 12, 2018)
12-88049037-TTTTA-T		Renal dysplasia and retinal aplasia • Leber congenital amaurosis • Familial aplasia of the vermis • Meckel-Gruber syndrome • Bardet-Biedl syndrome	Uncertain significance (Jun 14, 2016)
12-88049140-A-T		not specified	Likely benign (-)
12-88049161-GAAAC-G		not specified • Bardet-Biedl syndrome • Renal dysplasia and retinal aplasia • Meckel-Gruber syndrome • Familial aplasia of the vermis • Leber congenital amaurosis	Benign/Likely benign (May 10, 2018)
12-88049187-G-A		Nephronophthisis;Familial aplasia of the vermis;Meckel-Gruber syndrome	Likely benign (Mar 04, 2022)
12-88049194-G-C		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • CEP290-related disorder	Uncertain significance (Jun 29, 2022)
12-88049199-A-G		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis	Likely benign (Sep 27, 2022)
12-88049201-T-G		CEP290-related disorder	Uncertain significance (Aug 14, 2024)
12-88049202-A-G		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis	Likely benign (Sep 26, 2023)
12-88049208-A-G		Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis	Likely benign (Aug 20, 2022)
12-88049208-A-T		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • CEP290-related disorder	Uncertain significance (Aug 23, 2022)
12-88049210-TTTC-T		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • Leber congenital amaurosis	Uncertain significance (Aug 31, 2021)
12-88049211-TTC-T		Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis • CEP290-related disorder	Uncertain significance (Feb 24, 2022)
12-88049213-C-T		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • Retinal dystrophy • Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
12-88049227-A-G		Leber congenital amaurosis • Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis • CEP290-related disorder	Uncertain significance (Sep 13, 2022)
12-88049227-A-T		Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis • Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
12-88049226-A-AAACT		Meckel-Gruber syndrome;Familial aplasia of the vermis;Nephronophthisis	Uncertain significance (Aug 12, 2022)
12-88049228-ACT-A		not specified • Bardet-Biedl syndrome 14 • Joubert syndrome 5 • Nephronophthisis;Familial aplasia of the vermis;Meckel-Gruber syndrome • CEP290-related disorder	Conflicting classifications of pathogenicity (Aug 02, 2024)
12-88049228-A-ACTC		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis	Uncertain significance (Aug 23, 2023)
12-88049230-T-G		CEP290-related disorder	Uncertain significance (Aug 12, 2024)
12-88049231-C-CTG		Meckel-Gruber syndrome;Nephronophthisis;Familial aplasia of the vermis • Leber congenital amaurosis • CEP290-related disorder	Uncertain significance (Sep 30, 2024)
12-88049237-AAGC-A		Nephronophthisis;Familial aplasia of the vermis;Meckel-Gruber syndrome • Leber congenital amaurosis	Uncertain significance (Aug 31, 2022)
12-88049238-A-C		Familial aplasia of the vermis;Nephronophthisis;Meckel-Gruber syndrome	Likely benign (Jul 25, 2022)
12-88049244-A-T		Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis	Likely benign (Oct 16, 2023)
12-88049249-G-A		Senior-Loken syndrome 6 • Bardet-Biedl syndrome 14 • Joubert syndrome 5 • Leber congenital amaurosis 10 • Meckel syndrome, type 4 • Familial aplasia of the vermis;Meckel-Gruber syndrome;Nephronophthisis	Uncertain significance (Jul 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP290	protein_coding	protein_coding	ENST00000552810	53	93201

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.05e-60	0.00000370	124266	0	373	124639	0.00150

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.475	949	991	0.958	0.0000493	16290
Missense in Polyphen		323	340.96	0.94734		5715
Synonymous	0.133	327	330	0.991	0.0000154	4071
Loss of Function	1.69	104	124	0.837	0.00000639	1986

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00212	0.00208
Ashkenazi Jewish	0.0000997	0.0000994
East Asian	0.00339	0.00334
Finnish	0.000469	0.000464
European (Non-Finnish)	0.00181	0.00172
Middle Eastern	0.00339	0.00334
South Asian	0.00168	0.00157
Other	0.00140	0.00132

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332). Required for the correct localization of ciliary and phototransduction proteins in retinal photoreceptor cells; may play a role in ciliary transport processes (By similarity). Required for efficient recruitment of RAB8A to primary cilium (PubMed:17705300). In the ciliary transition zone is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2, BBS5 and BBS8/TTC8 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating IQCB1/NPHP5 (PubMed:25552655). Activates ATF4-mediated transcription (PubMed:16682973). {ECO:0000250|UniProtKB:Q6A078, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17705300, ECO:0000269|PubMed:18694559, ECO:0000269|PubMed:24421332, ECO:0000269|PubMed:25552655}.
• Disease: DISEASE: Joubert syndrome 5 (JBTS5) [MIM:610188]: 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 and renal disease. Joubert syndrome type 5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis. {ECO:0000269|PubMed:16682970, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:22425360, ECO:0000269|PubMed:26166481, ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Senior-Loken syndrome 6 (SLSN6) [MIM:610189]: A renal- retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269|PubMed:20683928}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber congenital amaurosis 10 (LCA10) [MIM:611755]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:16909394}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 4 (MKS4) [MIM:611134]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:17564974}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Antibodies against CEP290 are present in sera from patients with cutaneous T-cell lymphomas, but not in the healthy control population. {ECO:0000269|PubMed:11149944}.; DISEASE: Bardet-Biedl syndrome 14 (BBS14) [MIM:615991]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:18327255}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pathways in clear cell renal cell carcinoma;Neutrophil degranulation;Innate Immune System;Immune System;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.311

Intolerance Scores

• loftool: 0.693
• rvis_EVS: 0.37
• rvis_percentile_EVS: 75.31

Haploinsufficiency Scores

• pHI: 0.484
• hipred: N
• hipred_score: 0.378
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.907

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cep290
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; taste/olfaction phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; pigmentation phenotype

Zebrafish Information Network

• Gene name: cep290
• Affected structure: pronephric tubule
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;regulation of G2/M transition of mitotic cell cycle;protein transport;hindbrain development;otic vesicle formation;eye photoreceptor cell development;neutrophil degranulation;positive regulation of transcription, DNA-templated;pronephros development;cilium assembly;regulation of establishment of protein localization;positive regulation of intracellular protein transport;ciliary basal body-plasma membrane docking
• Cellular component: gamma-tubulin complex;extracellular region;nucleus;cytoplasm;centrosome;centriole;cytosol;membrane;photoreceptor connecting cilium;protein-containing complex;centriolar satellite;specific granule lumen;ciliary transition zone;MKS complex;ciliary basal body
• Molecular function: protein binding;identical protein binding;microtubule minus-end binding