PCNA (Proliferating Cell Nuclear Antigen)
A key regulator of DNA replication and repair, with implications in cancer and proliferative disorders.
Gene Information Card
| Symbol | PCNA |
|---|---|
| Full Name | Proliferating Cell Nuclear Antigen |
| Gene Type | Protein-coding |
| Chromosomal Location | 20p12.3 |
| NCBI Gene ID | 5111 ncbi.nlm.nih.gov/gene/5111 |
| Ensembl ID | ENSG00000132646 |
| UniProt ID | P12004 |
| OMIM ID | 176740 |
| HGNC ID | 8729 |
| Aliases | ATLD2, MGC8367, PCNA-AS1 |
Description
The PCNA gene encodes proliferating cell nuclear antigen, a homotrimeric protein that functions as a sliding clamp for DNA polymerase delta during DNA replication. It is essential for DNA synthesis, repair, and cell cycle regulation. PCNA interacts with multiple partners involved in chromatin remodeling, DNA damage response, and cell cycle control. Its expression is elevated in proliferating cells and is widely used as a marker for cell proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ataxia-telangiectasia-like disorder 2 (ATLD2) | Mutations in PCNA impair DNA repair and replication, leading to genomic instability and neurological symptoms. | OMIM #615919 |
| Lung cancer | Overexpression of PCNA is associated with increased cell proliferation and poor prognosis. | COSMIC, ClinVar |
| Breast cancer | Elevated PCNA expression correlates with tumor grade and aggressiveness. | COSMIC, ClinVar |
| Colorectal cancer | PCNA overexpression is linked to tumor progression and metastasis. | COSMIC, ClinVar |
| Prostate cancer | PCNA is upregulated in prostate cancer and associated with recurrence. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 42.3 | High |
| Bone marrow | 38.1 | High |
| Lymph node | 35.7 | High |
| Spleen | 30.2 | High |
| Small intestine | 28.9 | High |
| Colon | 25.4 | Medium |
| Lung | 18.6 | Medium |
| Breast | 12.3 | Medium |
| Liver | 8.7 | Low |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 58.2 | Cervical cancer cell line; high expression |
| K562 | 52.1 | Leukemia cell line; high expression |
| A549 | 45.6 | Lung cancer cell line; high expression |
| MCF7 | 40.3 | Breast cancer cell line; high expression |
| HEK293 | 35.8 | Embryonic kidney cell line; moderate expression |
| HepG2 | 30.4 | Liver cancer cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.331G>A (p.Glu111Lys) | Missense | <0.01% | Impairs PCNA trimerization and DNA repair; associated with ATLD2 |
| c.497A>G (p.Asn166Ser) | Missense | <0.01% | Reduces interaction with DNA polymerase delta; linked to replication defects |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of translation initiation; likely loss-of-function |
| c.724C>T (p.Arg242Cys) | Missense | <0.01% | Alters PCNA ubiquitination; affects translesion synthesis |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt PCNA trimerization or DNA binding (e.g., p.Glu111Lys) lead to loss of sliding clamp function, impairing DNA replication and repair.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported; overexpression in tumors is considered a secondary effect of proliferation.
Dominant Negative (DN)
Some missense mutations (e.g., p.Asn166Ser) can interfere with wild-type PCNA function in a dominant-negative manner, disrupting replication fork progression.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA replication (KEGG: hsa03030)
• Base excision repair (KEGG: hsa03410)
• Nucleotide excision repair (KEGG: hsa03420)
• Mismatch repair (KEGG: hsa03430)
• Fanconi anemia pathway (KEGG: hsa03460)
• p53 signaling pathway (KEGG: hsa04115)
• Cell cycle (KEGG: hsa04110)
Protein Summary
PCNA is a 261-amino acid protein that forms a homotrimeric ring structure encircling DNA, acting as a sliding clamp for DNA polymerase delta. It is essential for processive DNA replication and coordinates DNA repair pathways including base excision repair, nucleotide excision repair, and mismatch repair. PCNA is modified by ubiquitination and SUMOylation to regulate translesion synthesis and chromatin dynamics. Its expression is tightly linked to cell proliferation, making it a common immunohistochemical marker in cancer diagnostics.
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