CEP250

centrosomal protein 250

Basic information

Region (hg38): 20:35455164-35519280

Previous symbols: [ "CEP2" ]

Links

ENSG00000126001 ∙ NCBI:11190 ∙ OMIM:609689 ∙ HGNC:1859 ∙ Uniprot:Q9BV73 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy and hearing loss 2 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Limited), mode of inheritance: AR
• cone-rod dystrophy and hearing loss 2 (Limited), mode of inheritance: AR
• male infertility with azoospermia or oligozoospermia due to single gene mutation (Disputed Evidence), mode of inheritance: AR
• cone-rod dystrophy and hearing loss 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod dystrophy and hearing loss 2	AR	Audiologic/Otolaryngologic	The condition can involve early-onset hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	24780881; 28005958; 29718797; 30459346

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP250 gene.

• not provided (55 variants)
• Cone-rod dystrophy and hearing loss 2 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP250 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	346	16	363
missense			684	16	19	719
nonsense	30	4	1			35
start loss						0
frameshift	25	1	4			30
inframe indel			10	1	1	12
splice donor/acceptor (+/-2bp)	1	10				11
splice region			25	43	4	72
non coding				129	23	152
Total	56	15	700	492	59

Highest pathogenic variant AF is 0.000177

Variants in CEP250

This is a list of pathogenic ClinVar variants found in the CEP250 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-35462373-G-A			Likely benign (May 23, 2020)
20-35462382-C-T			Likely benign (Sep 29, 2023)
20-35462391-G-A			Likely benign (Jul 27, 2021)
20-35462397-C-A			Uncertain significance (Jul 27, 2022)
20-35462397-C-T			Likely benign (Nov 29, 2022)
20-35462416-C-A			Uncertain significance (Jul 17, 2023)
20-35462418-G-C			Uncertain significance (Jan 28, 2022)
20-35462422-G-C		not specified	Uncertain significance (Sep 30, 2021)
20-35462425-C-T			Likely benign (Feb 03, 2022)
20-35462437-G-T		not specified	Uncertain significance (Nov 14, 2024)
20-35462439-G-T			Likely benign (Aug 06, 2022)
20-35462440-C-G		not specified	Uncertain significance (Dec 19, 2023)
20-35462440-C-T			Likely benign (Apr 29, 2023)
20-35462457-G-C			Uncertain significance (Jun 01, 2022)
20-35462459-T-TG			Pathogenic (Oct 03, 2023)
20-35462466-G-T			Uncertain significance (Jan 14, 2021)
20-35462467-A-G		not specified	Uncertain significance (Apr 04, 2024)
20-35462473-G-A			Uncertain significance (May 17, 2022)
20-35462485-C-T		Retinal dystrophy	Uncertain significance (Jan 01, 2023)
20-35462486-G-A			Uncertain significance (Aug 18, 2021)
20-35462490-G-C			Uncertain significance (Oct 23, 2021)
20-35462506-G-A			Uncertain significance (Oct 30, 2023)
20-35462525-C-A			Uncertain significance (Nov 19, 2021)
20-35462567-C-G			Likely benign (Mar 03, 2022)
20-35462568-C-G			Likely benign (Oct 09, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP250	protein_coding	protein_coding	ENST00000397527	32	56820

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.45e-33	1.00	125450	0	298	125748	0.00119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	1136	1.27e+3	0.895	0.0000726	15721
Missense in Polyphen		332	394.36	0.84187		5341
Synonymous	2.44	451	522	0.864	0.0000266	4791
Loss of Function	5.17	77	144	0.535	0.00000809	1476

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00257	0.00254
Ashkenazi Jewish	0.000302	0.000298
East Asian	0.000882	0.000870
Finnish	0.00324	0.00273
European (Non-Finnish)	0.00102	0.00100
Middle Eastern	0.000882	0.000870
South Asian	0.000665	0.000621
Other	0.00185	0.00179

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably plays an important role in centrosome cohesion during interphase.
• Pathway: Mesodermal Commitment 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: 0.112

Intolerance Scores

• loftool: 0.939
• rvis_EVS: -0.77
• rvis_percentile_EVS: 13.17

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.328
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cep250

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;mitotic cell cycle;protein localization;regulation of G2/M transition of mitotic cell cycle;centriole-centriole cohesion;regulation of centriole-centriole cohesion;protein localization to organelle;ciliary basal body-plasma membrane docking;positive regulation of protein localization to centrosome;non-motile cilium assembly
• Cellular component: centrosome;centriole;microtubule organizing center;cytosol;cilium;protein-containing complex;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: protein binding;protein C-terminus binding;protein kinase binding;protein domain specific binding