CENPP

protein-coding

centromere protein P, the group of Constitutive centromere associated network

Gene summary

CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001012267.3

Inheritance

—

ClinVar variants

P:1U:48B:9

Top phenotype

ASPN-related disorder

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr9:92,325,953-92,620,529

External References & Databases

Ensembl (ENSG00000188312)

Transcript & Mutation Effects

hg38 • Region Span ~294.6 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 CENPP variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 242

ASPN-related disorderTotal: 5

CENPP-related disorderTotal: 4

not providedTotal: 3

Low-frequency sensorineural hearing impairmentTotal: 1

Low-frequency hearing lossTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012267.3. 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			1 clinvar			1
missense			44 clinvar	9 clinvar		53
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	48	9	0	58

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012267.3	RefSeq	NP_001012267.1	8	MANE Select
ENST00000375587.8	Ensembl	ENSP00000364737.3	8	MANE Select
NM_001286969.1	RefSeq	NP_001273898.1	6	Standard
NM_001286971.1	RefSeq	NP_001273900.1	4	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

chromosome, centromeric region
nucleus
nucleoplasm
nucleolus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375587
Coding exons: 8
Length: 295050
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.320	138	149	0.926	0.00000766	1866
Missense (PolyPhen)		13	12.945	1.0042		160
Synonymous	0.0210	56	56.2	0.996	0.00000295	538
Loss of Function	2.47	5	15.5	0.322	7.44e-7	189

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00041	0.00039	rare
Other	0	0.0	absent

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. {ECO:0000269|PubMed:16622420}.;

Recessive Scores

pRec: 0.0755

Intolerance Scores

LoFtool: 0.311
RVIS EVS: 0.44
RVIS percentile EVS: 77.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.404

Gene Damage Prediction

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