CENPO

protein-coding

centromere protein O, the group of Constitutive centromere associated network

Gene summary

This gene encodes a component of the interphase centromere complex. The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MANE transcript

NM_001322101.2

Inheritance

—

ClinVar variants

U:35B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr2:24,793,136-24,822,376

External References & Databases

Ensembl (ENSG00000138092)

Transcript & Mutation Effects

hg38 • Region Span ~29.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CENPO variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 36

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001322101.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			32 clinvar	7 clinvar		39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	35	7	0	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001322101.2	RefSeq	NP_001309030.1	6	MANE Select
ENST00000380834.7	Ensembl	ENSP00000370214.2	6	MANE Select
NM_001199803.3	RefSeq	NP_001186732.1	6	Standard
NM_024322.4	RefSeq	NP_077298.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
Amplification of signal from the kinetochores
Mitotic Spindle Checkpoint
Cell Cycle Checkpoints

Biological Process

CENP-A containing nucleosome assembly

Molecular Function

protein binding

Cellular Component

condensed nuclear chromosome kinetochore
condensed nuclear chromosome, centromeric region
nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380834
Coding exons: 6
Length: 29241
Individuals with no LoFs: 125594
Homozygous LoFs: 1
Heterozygous LoFs: 153
Defined: 125748
p: 0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.404	148	163	0.911	0.00000874	1925
Missense (PolyPhen)		31	40.723	0.76123		552
Synonymous	-0.707	73	65.7	1.11	0.00000335	604
Loss of Function	0.619	15	17.8	0.842	0.00000121	179

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0021	0.0021	notable
Latino/Admixed American	0.0012	0.0011	notable
Ashkenazi Jewish	0.0040	0.0040	notable
East Asian	0.00022	0.00022	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00030	0.00029	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Modulates the kinetochore-bound levels of NDC80 complex. {ECO:0000269|PubMed:16622420, ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:16932742, ECO:0000269|PubMed:18007590}.;

Recessive Scores

pRec: 0.0640

Intolerance Scores

LoFtool: 0.879
RVIS EVS: 0.02
RVIS percentile EVS: 55.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.799

Gene Damage Prediction

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