CEP152

centrosomal protein 152

Basic information

Region (hg38): 15:48712928-48811146

Links

ENSG00000103995

∙ NCBI:22995 ∙ OMIM:613529 ∙ HGNC:29298 ∙ Uniprot:O94986 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
Seckel syndrome (Supportive), mode of inheritance: AR
microcephaly 9, primary, autosomal recessive (Strong), mode of inheritance: AR
microcephaly with or without short stature (Definitive), mode of inheritance: AR
Seckel syndrome 5 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Seckel syndrome 5; Microcephaly 9, primary, autosomal recessive	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	20598275; 21131973

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP152 gene.

not_provided (957 variants)
Inborn_genetic_diseases (172 variants)
Microcephaly_9,_primary,_autosomal_recessive (155 variants)
Seckel_syndrome_5 (117 variants)
not_specified (65 variants)
CEP152-related_disorder (48 variants)
Seckel_syndrome (2 variants)
Primary_Microcephaly,_Recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP152 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001194998.2. 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	1 clinvar		5 clinvar	378 clinvar	3 clinvar	387
missense	2 clinvar	2 clinvar	301 clinvar	40 clinvar	4 clinvar	349
nonsense	35 clinvar	15 clinvar	1 clinvar	3 clinvar		54
start loss						0
frameshift	49 clinvar	13 clinvar	2 clinvar	9 clinvar		73
splice donor/acceptor (+/-2bp)	3 clinvar	27 clinvar	2 clinvar			32
Total	90	57	311	430	7

Highest pathogenic variant AF is 0.000283751

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP152	protein_coding	protein_coding	ENST00000380950	26	98219

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-27	0.965	124446	0	349	124795	0.00140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0279	831	833	0.997	0.0000421	11378
Missense in Polyphen		272	275.17	0.98849		3976
Synonymous	-0.329	305	298	1.02	0.0000155	2973
Loss of Function	2.91	56	85.0	0.659	0.00000447	1047

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00379	0.00379
Ashkenazi Jewish	0.000794	0.000795
East Asian	0.00373	0.00362
Finnish	0.000329	0.000325
European (Non-Finnish)	0.00116	0.00111
Middle Eastern	0.00373	0.00362
South Asian	0.00177	0.00177
Other	0.00165	0.00165

dbNSFP

Source: dbNSFP

Function: FUNCTION: Necessary for centrosome duplication; the function seems also to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation (PubMed:21059844, PubMed:20852615). Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure (PubMed:24997597). Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (By similarity). Overexpression of CEP152 can drive amplification of centrioles (PubMed:20852615). {ECO:0000250|UniProtKB:A2AUM9, ECO:0000250|UniProtKB:Q498G2, ECO:0000269|PubMed:20852615, ECO:0000269|PubMed:21059844, ECO:0000269|PubMed:21131973}.;
Disease: DISEASE: Microcephaly 9, primary, autosomal recessive (MCPH9) [MIM:614852]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. {ECO:0000269|PubMed:20598275}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Seckel syndrome 5 (SCKL5) [MIM:613823]: 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:21131973}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: 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: 0.100

Intolerance Scores

loftool: 0.979
rvis_EVS: 0.97
rvis_percentile_EVS: 90.24

Haploinsufficiency Scores

pHI: 0.166
hipred: N
hipred_score: 0.230
ghis: 0.567

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: N
gene_indispensability_score: 0.224

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cep152
Phenotype: embryo 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); cellular phenotype;

Gene ontology

Biological process: G2/M transition of mitotic cell cycle;centriole replication;regulation of G2/M transition of mitotic cell cycle;centrosome duplication;ciliary basal body-plasma membrane docking;de novo centriole assembly involved in multi-ciliated epithelial cell differentiation
Cellular component: pericentriolar material;nucleoplasm;centrosome;centriole;cytosol;deuterosome
Molecular function: protein binding;protein kinase binding