CEP135

centrosomal protein 135

Basic information

Region (hg38): 4:55948871-56033361

Previous symbols: [ "KIAA0635", "CEP4" ]

Links

ENSG00000174799 ∙ NCBI:9662 ∙ OMIM:611423 ∙ HGNC:29086 ∙ Uniprot:Q66GS9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 8, primary, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• microcephaly 8, primary, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 8, 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	22521416

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP135 gene.

• not_provided (373 variants)
• Inborn_genetic_diseases (152 variants)
• not_specified (35 variants)
• Microcephaly_8,_primary,_autosomal_recessive (28 variants)
• CEP135-related_disorder (23 variants)
• Auditory_neuropathy_spectrum_disorder (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP135 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025009.5. 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			3	89	2	94
missense		2	215	31	2	250
nonsense	10	8	3			21
start loss						0
frameshift	19	8				27
splice donor/acceptor (+/-2bp)	1	10	1			12
Total	30	28	222	120	4

Highest pathogenic variant AF is 0.0000849073

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP135	protein_coding	protein_coding	ENST00000257287	24	84493

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.59e-22	0.986	125511	0	237	125748	0.000943

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0804	565	570	0.991	0.0000298	7475
Missense in Polyphen		175	181.33	0.96512		2513
Synonymous	0.804	180	194	0.927	0.00000943	2027
Loss of Function	2.87	46	72.4	0.635	0.00000453	883

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00439	0.00436
Ashkenazi Jewish	0.000399	0.000397
East Asian	0.00203	0.00201
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000731	0.000712
Middle Eastern	0.00203	0.00201
South Asian	0.00100	0.000980
Other	0.000512	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in early centriole assembly/duplication/biogenesis/formation/. Required for centriole elongation. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner. {ECO:0000269|PubMed:27185865}.
• Disease: DISEASE: Microcephaly 8, primary, autosomal recessive (MCPH8) [MIM:614673]: 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:22521416}. 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: 0.117

Intolerance Scores

• loftool: 0.995
• rvis_EVS: 0.43
• rvis_percentile_EVS: 77.35

Haploinsufficiency Scores

• pHI: 0.658
• hipred: Y
• hipred_score: 0.516
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.865

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cep135

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;centriole replication;regulation of G2/M transition of mitotic cell cycle;centriole-centriole cohesion;ciliary basal body-plasma membrane docking;positive regulation of non-motile cilium assembly;positive regulation of establishment of protein localization
• Cellular component: centrosome;centriole;cytosol
• Molecular function: protein binding;protein C-terminus binding