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.

• Meckel-Gruber_syndrome (3166 variants)
• Nephronophthisis (3165 variants)
• Joubert_syndrome (3165 variants)
• Bardet-Biedl_syndrome_14 (1018 variants)
• Joubert_syndrome_5 (817 variants)
• Meckel_syndrome,_type_4 (789 variants)
• Leber_congenital_amaurosis_10 (786 variants)
• Senior-Loken_syndrome_6 (770 variants)
• CEP290-related_disorder (607 variants)
• Leber_congenital_amaurosis (589 variants)
• not_provided (542 variants)
• Inborn_genetic_diseases (296 variants)
• Retinal_dystrophy (183 variants)
• not_specified (163 variants)
• CEP290-related_ciliopathy (37 variants)
• Retinitis_pigmentosa (24 variants)
• Intellectual_disability (15 variants)
• Joubert_syndrome_1 (14 variants)
• Kidney_disorder (13 variants)
• Renal_dysplasia_and_retinal_aplasia (6 variants)
• Bardet-Biedl_syndrome (6 variants)
• Rod-cone_dystrophy (4 variants)
• Optic_atrophy (4 variants)
• Polycystic_kidney_disease (4 variants)
• Blindness (4 variants)
• See_cases (3 variants)
• Occipital_encephalocele (3 variants)
• Global_developmental_delay (3 variants)
• Meckel_syndrome,_type_6 (3 variants)
• Cerebellar_cyst (2 variants)
• Cerebellar_vermis_hypoplasia (2 variants)
• Encephalocele (2 variants)
• Abnormality_of_the_nervous_system (2 variants)
• Abnormality_of_the_kidney (2 variants)
• Hyperechogenic_kidneys (2 variants)
• Abnormality_of_prenatal_development_or_birth (2 variants)
• Central_hypotonia (2 variants)
• Genetic_developmental_and_epileptic_encephalopathy (2 variants)
• Cystic_renal_dysplasia (2 variants)
• Molar_tooth_sign_on_MRI (2 variants)
• Nystagmus (2 variants)
• Severe_hydrocephalus (2 variants)
• Stuve-Wiedemann_syndrome_2 (2 variants)
• Atypical_hemolytic-uremic_syndrome (1 variants)
• Night_blindness (1 variants)
• Microcephaly (1 variants)
• CEP20-related_disorder (1 variants)
• Senior-Loken_syndrome_1 (1 variants)
• COG7_congenital_disorder_of_glycosylation (1 variants)
• Cone-rod_dystrophy (1 variants)
• Abnormal_facial_shape (1 variants)
• Retinal_disorder (1 variants)
• CEP290-related_ciliopathies (1 variants)
• Hypotonia (1 variants)
• Joubert_syndrome_and_related_disorders (1 variants)
• Micrognathia (1 variants)
• Spastic_ataxia (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. These statistics are base on transcript: NM_000025114.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	2	1	63	895	3	964
missense	6	21	1308	51	5	1391
nonsense	178	112	5			295
start loss	1	3				4
frameshift	214	220	10	1		445
splice donor/acceptor (+/-2bp)	34	122	4	1		161
Total	435	479	1390	948	8

Highest pathogenic variant AF is 0.0005882249

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