CENPA

centromere protein A, the group of Constitutive centromere associated network|H3 histones

Basic information

Region (hg38): 2:26764289-26801067

Links

ENSG00000115163 ∙ NCBI:1058 ∙ OMIM:117139 ∙ HGNC:1851 ∙ Uniprot:P49450 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CENPA 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						0
missense			8	1		9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	1	0

Variants in CENPA

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

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

Position	Type	Phenotype	Significance	ClinVar
2-26764388-C-T			Likely benign (Apr 01, 2023)
2-26764414-C-A		not specified	Uncertain significance (Feb 15, 2023)
2-26774252-T-C		not specified	Uncertain significance (Apr 08, 2024)
2-26774273-G-A		not specified	Uncertain significance (Dec 27, 2022)
2-26774283-G-C		not specified	Uncertain significance (Jan 09, 2024)
2-26775068-T-G		not specified	Uncertain significance (Apr 20, 2024)
2-26775071-T-A		not specified	Uncertain significance (Jan 01, 2025)
2-26775107-G-A		not specified	Uncertain significance (Apr 13, 2022)
2-26775536-C-G		not specified	Uncertain significance (Jan 01, 2025)
2-26775554-G-A		not specified	Uncertain significance (Jul 12, 2022)
2-26775598-G-C		not specified	Uncertain significance (Dec 06, 2022)
2-26775599-C-T		not specified	Uncertain significance (Aug 12, 2024)
2-26775613-G-T		not specified	Uncertain significance (May 07, 2024)
2-26775632-T-A		not specified	Uncertain significance (Aug 30, 2021)
2-26775671-T-C		not specified	Uncertain significance (Oct 04, 2024)
2-26776381-T-C		not specified	Uncertain significance (Dec 17, 2023)
2-26776386-A-C		not specified	Uncertain significance (Jan 24, 2025)
2-26776408-C-G		not specified	Uncertain significance (May 26, 2024)
2-26776457-C-G		not specified	Uncertain significance (Nov 11, 2024)
2-26776464-C-T		not specified	Uncertain significance (Feb 24, 2023)
2-26776470-G-T		not specified	Uncertain significance (Sep 01, 2021)
2-26778062-C-T		not specified	Uncertain significance (Sep 09, 2021)
2-26778092-A-G		not specified	Uncertain significance (Dec 18, 2023)
2-26778101-G-A		not specified	Uncertain significance (Dec 20, 2022)
2-26778105-C-T		not specified	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CENPA	protein_coding	protein_coding	ENST00000335756	4	36779

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0115	0.856	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.73	31	72.3	0.429	0.00000453	879
Missense in Polyphen		6	32.761	0.18315		359
Synonymous	0.0705	26	26.5	0.983	0.00000132	307
Loss of Function	1.23	4	7.67	0.521	5.00e-7	77

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000640	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:7962047, PubMed:9024683, PubMed:11756469, PubMed:14667408, PubMed:15702419, PubMed:15475964, PubMed:15282608, PubMed:17651496, PubMed:19114591, PubMed:27499292, PubMed:20739937). Replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore (PubMed:18072184). The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3 (PubMed:27499292, PubMed:26878239). May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:15475964, PubMed:15282608, PubMed:26878239, PubMed:20739937, PubMed:21478274). Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18072184, PubMed:23818633, PubMed:25556658, PubMed:27499292). {ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:14667408, ECO:0000269|PubMed:15282608, ECO:0000269|PubMed:15475964, ECO:0000269|PubMed:15702419, ECO:0000269|PubMed:17651496, ECO:0000269|PubMed:18072184, ECO:0000269|PubMed:19114591, ECO:0000269|PubMed:21478274, ECO:0000269|PubMed:23818633, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26878239, ECO:0000269|PubMed:27499292, ECO:0000269|PubMed:7962047, ECO:0000269|PubMed:9024683, ECO:0000305|PubMed:20739937}.
• Pathway: 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;RHO GTPases Activate Formins;Aurora A signaling;Nucleosome assembly;RHO GTPase Effectors;Signaling by Rho GTPases;Chromosome Maintenance;Deposition of new CENPA-containing nucleosomes at the centromere;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;Aurora B signaling;FOXM1 transcription factor network (Consensus)

Recessive Scores

• pRec: 0.0790

Intolerance Scores

• loftool: 0.639
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.678
• hipred: Y
• hipred_score: 0.628
• ghis: 0.700

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cenpa
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: establishment of mitotic spindle orientation;mitotic cytokinesis;viral process;CENP-A containing nucleosome assembly;kinetochore assembly;protein localization to chromosome, centromeric region
• Cellular component: chromosome, centromeric region;condensed nuclear chromosome kinetochore;condensed nuclear chromosome, centromeric region;nucleosome;nuclear nucleosome;condensed chromosome inner kinetochore;nucleus;nucleoplasm;cytosol;nuclear pericentric heterochromatin
• Molecular function: chromatin binding;protein binding;nucleosomal DNA binding;protein heterodimerization activity