POLA2: DNA Polymerase Alpha 2 Subunit
Essential component of the DNA polymerase alpha-primase complex involved in DNA replication initiation
Gene Information Card
| Symbol | POLA2 |
|---|---|
| Full Name | DNA polymerase alpha 2, accessory subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 23649 ncbi.nlm.nih.gov/gene/23649 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q14181 |
| OMIM ID | 604840 |
| HGNC ID | 9173 |
| Aliases | POLA2, p70, DNA polymerase alpha 70 kDa subunit |
Description
POLA2 encodes the 70 kDa accessory subunit of DNA polymerase alpha, a component of the DNA polymerase alpha-primase complex. This complex is essential for the initiation of DNA replication, as it synthesizes RNA-DNA primers for Okazaki fragments on the lagging strand. POLA2 stabilizes the complex and contributes to primer synthesis and polymerase processivity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Somatic mutations in POLA2 may impair replication fidelity, leading to genomic instability | COSMIC, ClinVar |
| Breast cancer | Altered expression and mutations reported; potential role in tumorigenesis | COSMIC |
| Lung adenocarcinoma | Copy number alterations and missense variants observed | COSMIC |
| Gastric cancer | Reduced expression linked to replication stress | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 10.2 | Medium |
| Lymph node | 9.8 | Medium |
| Brain | 6.3 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical carcinoma; high expression |
| K562 | 11.7 | Leukemia; moderate expression |
| A549 | 9.4 | Lung carcinoma; moderate expression |
| MCF7 | 8.1 | Breast cancer; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234G>A (p.Gly412Arg) | Missense | 0.02% | Unknown functional impact; reported in COSMIC |
| c.567_568insA | Frameshift | <0.01% | Predicted loss of function |
| c.890C>T (p.Thr297Met) | Missense | 0.01% | May affect protein stability |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein likely impair DNA replication initiation and cause genomic instability.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported in POLA2.
Dominant Negative (DN)
Missense mutations in conserved domains may disrupt complex assembly, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication initiation | • DNA primase activity |
| • DNA-directed DNA polymerase activity | • protein binding |
| • nucleus | • alpha DNA polymerase:primase complex |
Pathways
• DNA replication (KEGG hsa03030)
• Cell cycle (KEGG hsa04110)
• Base excision repair (Reactome R-HSA-73894)
Protein Summary
POLA2 encodes the 70 kDa accessory subunit of DNA polymerase alpha. This subunit is essential for the stability and activity of the polymerase alpha-primase complex, which initiates DNA replication by synthesizing RNA-DNA primers. The protein localizes to the nucleus and interacts with other subunits (POLA1, PRIM1, PRIM2). Defects in POLA2 can lead to replication stress and genomic instability, with somatic mutations observed in various cancers.
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