CENPE

centromere protein E, the group of Kinesins|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 4:103105348-103198445

Links

ENSG00000138778 ∙ NCBI:1062 ∙ OMIM:117143 ∙ HGNC:1856 ∙ Uniprot:Q02224 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 13, primary, autosomal recessive (Limited), mode of inheritance: AR
• microcephaly 13, primary, autosomal recessive (Limited), mode of inheritance: AR
• Seckel syndrome (Supportive), mode of inheritance: AR
• microcephaly 13, primary, autosomal recessive (Limited), mode of inheritance: Unknown
• autosomal recessive primary microcephaly (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 13, 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	24748105

ClinVar

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

• not provided (242 variants)
• Inborn genetic diseases (67 variants)
• not specified (28 variants)
• Microcephaly 13, primary, autosomal recessive (15 variants)
• CENPE-related condition (4 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CENPE 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				45	8	53
missense		2	110	15	8	135
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1	6	5	12
non coding				59	58	117
Total	0	3	115	119	74

Highest pathogenic variant AF is 0.000151

Variants in CENPE

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

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

Position	Type	Phenotype	Significance	ClinVar
4-103106248-C-T			Likely benign (Dec 01, 2023)
4-103106279-C-T			Likely benign (Jun 23, 2018)
4-103106287-C-G			Uncertain significance (Jun 03, 2022)
4-103106487-G-A			Benign (Jul 17, 2018)
4-103108582-G-C			Benign (Jul 26, 2018)
4-103108588-CTAAA-C			Benign (Jul 26, 2018)
4-103108806-G-A			Uncertain significance (Dec 01, 2020)
4-103108838-C-T		not specified	Uncertain significance (Oct 10, 2023)
4-103108855-T-C			Likely benign (Oct 12, 2018)
4-103108896-G-A		not specified	Uncertain significance (Oct 06, 2022)
4-103108928-C-T		not specified	Conflicting classifications of pathogenicity (Feb 01, 2024)
4-103108930-T-G		not specified	Uncertain significance (Oct 20, 2023)
4-103108987-A-C			Likely benign (Jun 08, 2018)
4-103108993-C-T			Likely benign (Mar 28, 2018)
4-103109041-G-C			Likely benign (Aug 13, 2018)
4-103109050-C-T			Benign/Likely benign (Mar 01, 2021)
4-103109082-G-C			Uncertain significance (Aug 01, 2021)
4-103109236-A-C			Likely benign (Dec 03, 2020)
4-103110812-T-C			Likely benign (Dec 03, 2020)
4-103110906-T-A		not specified	Uncertain significance (Apr 28, 2023)
4-103110925-G-T		not specified	Uncertain significance (Jan 04, 2024)
4-103110949-C-T			Uncertain significance (Mar 01, 2023)
4-103110950-G-A		not specified	Benign/Likely benign (Apr 15, 2021)
4-103110959-T-A		CENPE-related disorder	Likely benign (Jun 29, 2021)
4-103110996-G-T			Uncertain significance (Apr 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CENPE	protein_coding	protein_coding	ENST00000265148	49	92604

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.241	0.759	125642	0	96	125738	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	1113	1.24e+3	0.899	0.0000588	18071
Missense in Polyphen		204	324.56	0.62853		4867
Synonymous	-0.643	438	421	1.04	0.0000199	4540
Loss of Function	8.44	32	140	0.229	0.00000689	1972

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000566	0.000558
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000336	0.000317
Middle Eastern	0.000164	0.000163
South Asian	0.00146	0.00118
Other	0.000356	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule- kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules (PubMed:7889940, PubMed:23891108, PubMed:25395579). The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated (PubMed:25908662). Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends (PubMed:23955301). Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized (PubMed:25743205). Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules (PubMed:17535814) The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss (By similarity). {ECO:0000250|UniProtKB:Q6RT24, ECO:0000269|PubMed:17535814, ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:23955301, ECO:0000269|PubMed:25395579, ECO:0000269|PubMed:25743205, ECO:0000269|PubMed:25908662, ECO:0000269|PubMed:7889940}.
• Disease: DISEASE: Microcephaly 13, primary, autosomal recessive (MCPH13) [MIM:616051]: A form of microcephaly, 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. {ECO:0000269|PubMed:24748105}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of sister chromatid separation at the metaphase-anaphase transition;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Kinesins;Factors involved in megakaryocyte development and platelet production;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Hemostasis;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;PLK1 signaling events;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.801
• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.97

Haploinsufficiency Scores

• pHI: 0.799
• hipred: Y
• hipred_score: 0.691
• ghis: 0.620

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.835

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cenpe
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype

Gene ontology

• Biological process: mitotic cell cycle;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;microtubule-based movement;mitotic spindle organization;chromosome segregation;mitotic chromosome movement towards spindle pole;mitotic metaphase plate congression;multicellular organism development;antigen processing and presentation of exogenous peptide antigen via MHC class II;regulation of mitotic metaphase/anaphase transition;positive regulation of protein kinase activity;cell division;metaphase plate congression;attachment of mitotic spindle microtubules to kinetochore;kinetochore assembly;microtubule plus-end directed mitotic chromosome migration;lateral attachment of mitotic spindle microtubules to kinetochore
• Cellular component: chromosome, centromeric region;kinetochore;condensed chromosome kinetochore;condensed chromosome, centromeric region;nucleus;nucleoplasm;chromosome;kinetochore microtubule;cytosol;kinesin complex;microtubule;microtubule cytoskeleton;membrane;midbody;spindle midzone;mitotic spindle midzone
• Molecular function: microtubule motor activity;protein binding;ATP binding;microtubule binding;ATPase activity;kinetochore binding