CENPA: Centromere Protein A
Key Epigenetic Regulator of Centromere Identity and Chromosome Segregation
Gene Information Card
| Symbol | CENPA |
|---|---|
| Full Name | Centromere Protein A |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 1058 ncbi.nlm.nih.gov/gene/1058 |
| Ensembl ID | ENSG00000115163 |
| UniProt ID | P49450 |
| OMIM ID | 117139 |
| HGNC ID | 1851 |
| Aliases | CENP-A, CenH3, CENPA_HUMAN |
Description
CENPA encodes centromere protein A (CENP-A), a centromere-specific histone H3 variant that replaces conventional histone H3 in centromeric nucleosomes. CENP-A is essential for specifying centromere identity, recruiting kinetochore proteins, and ensuring accurate chromosome segregation during mitosis and meiosis. It is a key epigenetic marker of centromeres and is required for proper cell division.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of CENPA leads to centromere dysfunction and aneuploidy, promoting tumorigenesis. | PMID: 25691885 |
| Colorectal cancer | Elevated CENPA expression correlates with chromosomal instability and poor prognosis. | PMID: 29089132 |
| Hepatocellular carcinoma | CENPA upregulation is associated with aggressive tumor features and shorter survival. | PMID: 30733637 |
| Lung adenocarcinoma | CENPA overexpression contributes to mitotic defects and genomic instability. | PMID: 31570863 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Bone marrow | 8.2 | Medium |
| Lymph node | 6.1 | Medium |
| Spleen | 5.4 | Medium |
| Brain | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.3 | High expression; commonly used in centromere studies |
| K562 (leukemia) | 10.1 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 9.7 | Medium expression |
| MCF7 (breast cancer) | 12.8 | High expression; associated with proliferation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.274G>A (p.Gly92Arg) | Missense | <0.01% | Reported in ClinVar; functional impact unknown |
| c.1A>G (p.Met1Val) | Missense | <0.01% | Potential loss of start codon; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in CENPA; complete loss is likely lethal due to essential role in centromere function.
Gain of Function (GOF)
Overexpression of wild-type CENPA is observed in multiple cancers, acting as a gain-of-function by promoting centromere misregulation and aneuploidy.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; however, altered CENPA variants could disrupt centromere assembly.
View complete mutation data：
Gene Ontology (GO)
| • chromosome (GO:0000775) | • kinetochore (GO:0000776) |
| • CENP-A containing nucleosome (GO:0000780) | • nucleus (GO:0005634) |
| • chromosome (GO:0005694) | • nucleosome assembly (GO:0006334) |
| • cell cycle (GO:0007049) | • sister chromatid cohesion (GO:0007062) |
| • mitotic nuclear division (GO:0007067) | • centromere complex assembly (GO:0034508) |
Pathways
• Cell Cycle
• Mitotic (Reactome: R-HSA-69278)
• Mitotic Prometaphase (Reactome: R-HSA-68877)
• Chromosome Maintenance (Reactome: R-HSA-73886)
• Kinetochore Assembly (Reactome: R-HSA-141444)
Protein Summary
CENP-A is a 140-amino acid histone H3 variant that replaces canonical H3 in centromeric nucleosomes. It contains a conserved histone fold domain and a unique N-terminal tail that mediates interactions with centromere-specific proteins like CENP-C and the Mis18 complex. CENP-A is deposited at centromeres during the G1 phase of the cell cycle and is essential for kinetochore assembly and chromosome segregation. Its overexpression is linked to chromosomal instability and cancer progression.
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