CEP63
Basic information
Region (hg38): 3:134485699-134587789
Links
Phenotypes
GenCC
Source:
- Seckel syndrome 6 (Strong), mode of inheritance: AR
- Seckel syndrome 6 (Moderate), mode of inheritance: AR
- autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
- Seckel syndrome 6 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Seckel syndrome 6 | AR | General | 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 | Craniofacial; Musculoskeletal; Neurologic | 21983783 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (209 variants)
- Inborn_genetic_diseases (79 variants)
- not_specified (24 variants)
- Seckel_syndrome_6 (15 variants)
- CEP63-related_disorder (5 variants)
- Developmental_dyslexia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP63 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001353108.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 44 | 49 | ||||
missense | 137 | 10 | 149 | |||
nonsense | 12 | 16 | ||||
start loss | 0 | |||||
frameshift | 16 | |||||
splice donor/acceptor (+/-2bp) | 11 | |||||
Total | 20 | 17 | 146 | 54 | 4 |
Highest pathogenic variant AF is 0.0000805635
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
CEP63 | protein_coding | protein_coding | ENST00000337090 | 14 | 89275 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
6.24e-25 | 0.000713 | 125601 | 0 | 147 | 125748 | 0.000585 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.0983 | 366 | 361 | 1.01 | 0.0000180 | 4678 |
Missense in Polyphen | 97 | 95.255 | 1.0183 | 1258 | ||
Synonymous | 0.723 | 113 | 123 | 0.917 | 0.00000582 | 1223 |
Loss of Function | 0.216 | 38 | 39.5 | 0.963 | 0.00000191 | 494 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000924 | 0.000923 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000381 | 0.000381 |
Finnish | 0.0000462 | 0.0000462 |
European (Non-Finnish) | 0.000758 | 0.000756 |
Middle Eastern | 0.000381 | 0.000381 |
South Asian | 0.000787 | 0.000784 |
Other | 0.000817 | 0.000815 |
dbNSFP
Source:
- Function
- FUNCTION: Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication. Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398). {ECO:0000269|PubMed:21406398, ECO:0000269|PubMed:21983783, ECO:0000269|PubMed:26297806}.;
- Disease
- DISEASE: Seckel syndrome 6 (SCKL6) [MIM:614728]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269|PubMed:21983783}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- ATM Signaling Network in Development and Disease;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
- 0.108
Intolerance Scores
- loftool
- 1.00
- rvis_EVS
- -0.42
- rvis_percentile_EVS
- 25.73
Haploinsufficiency Scores
- pHI
- 0.183
- hipred
- N
- hipred_score
- 0.144
- ghis
- 0.514
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.347
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | High |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cep63
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region 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); reproductive system phenotype;
Gene ontology
- Biological process
- DNA damage checkpoint;G2/M transition of mitotic cell cycle;centriole replication;regulation of G2/M transition of mitotic cell cycle;signal transduction in response to DNA damage;spindle assembly;cell division;ciliary basal body-plasma membrane docking;de novo centriole assembly involved in multi-ciliated epithelial cell differentiation
- Cellular component
- spindle pole;centrosome;centriole;cytosol
- Molecular function
- protein binding