CEP63

centrosomal protein 63

Basic information

Region (hg38): 3:134485699-134587789

Links

ENSG00000182923 ∙ NCBI:80254 ∙ OMIM:614724 ∙ HGNC:25815 ∙ Uniprot:Q96MT8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the CEP63 gene.

• not provided (15 variants)
• Seckel syndrome 6 (1 variants)
• Inborn genetic diseases (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.

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			1	38	3	42
missense			99	5	4	108
nonsense	10	2	1			13
start loss						0
frameshift	7	2	2			11
inframe indel			2			2
splice donor/acceptor (+/-2bp)		7	1			8
splice region			7	7	3	17
non coding			1	13	32	46
Total	17	11	107	56	39

Highest pathogenic variant AF is 0.0000920

Variants in CEP63

This is a list of pathogenic ClinVar variants found in the CEP63 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-134495055-T-G			Benign (Nov 10, 2018)
3-134495139-T-C			Benign (May 10, 2021)
3-134495200-T-C			Benign (Nov 10, 2018)
3-134495325-A-T		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
3-134495343-T-C			Uncertain significance (Oct 13, 2023)
3-134495347-A-G			Likely benign (Feb 01, 2023)
3-134495351-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 28, 2022)
3-134495353-A-G			Likely benign (Nov 06, 2023)
3-134495358-A-G		Inborn genetic diseases	Uncertain significance (Jul 05, 2022)
3-134495360-G-A			Uncertain significance (Nov 28, 2023)
3-134495364-G-A			Uncertain significance (Apr 05, 2022)
3-134506843-G-A			Benign (Nov 10, 2018)
3-134506873-A-G			Benign (Nov 10, 2018)
3-134507120-C-T		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
3-134507125-T-G			Likely benign (Dec 15, 2023)
3-134507127-T-C		not specified	Benign (Jan 31, 2024)
3-134507154-A-G			Likely benign (Sep 04, 2022)
3-134507164-A-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
3-134507186-C-G			Uncertain significance (Aug 16, 2022)
3-134507193-G-A		Seckel syndrome 6	Pathogenic (Oct 09, 2011)
3-134507200-C-T			Uncertain significance (Jan 03, 2022)
3-134507201-G-A			Uncertain significance (Aug 15, 2022)
3-134507219-C-G			Uncertain significance (Aug 04, 2023)
3-134507224-T-C			Likely benign (Jun 26, 2018)
3-134507233-C-T			Uncertain significance (Nov 15, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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