POLQ (DNA Polymerase Theta)
A key player in DNA repair, replication, and cancer mutagenesis
Gene Information Card
| Symbol | POLQ |
|---|---|
| Full Name | DNA polymerase theta |
| Gene Type | Protein coding |
| Chromosomal Location | 3q22.3 |
| NCBI Gene ID | 10721 ncbi.nlm.nih.gov/gene/10721 |
| Ensembl ID | ENSG00000051341 |
| UniProt ID | O75417 |
| OMIM ID | 604419 |
| HGNC ID | 9186 |
| Aliases | TEBP, POLH, POLQ, MCPH10 |
Description
POLQ encodes DNA polymerase theta (Pol θ), a specialized A-family DNA polymerase with an N-terminal helicase-like domain and a C-terminal polymerase domain. Pol θ is the primary enzyme for microhomology-mediated end joining (MMEJ), an error-prone double-strand break repair pathway. It is also involved in translesion synthesis (TLS) and base excision repair. POLQ is frequently overexpressed in various cancers and is a target for synthetic lethality in BRCA-deficient tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | POLQ overexpression promotes MMEJ-dependent repair of replication-associated DSBs, compensating for HR deficiency in BRCA1/2-mutant tumors. | ClinVar, COSMIC, PMID: 25643323 |
| Ovarian cancer | High POLQ expression correlates with poor prognosis and platinum resistance; synthetic lethal interactions with PARP inhibitors. | ClinVar, COSMIC, PMID: 28991257 |
| Colorectal cancer | POLQ mutations and overexpression contribute to genomic instability and microsatellite instability. | COSMIC, PMID: 30349071 |
| Lung cancer | POLQ upregulation associated with increased mutational burden and poor survival. | COSMIC, PMID: 31570879 |
| Microcephaly, primary, autosomal recessive 10 (MCPH10) | Biallelic loss-of-function mutations in POLQ cause microcephaly, impaired DNA repair, and neurodevelopmental defects. | OMIM #604419, PMID: 27545674 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Bone marrow | 8.7 | Low |
| Lymph node | 6.2 | Low |
| Ovary | 5.1 | Low |
| Breast | 3.8 | Low |
| Colon | 2.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.2 | High expression |
| MCF7 (breast cancer) | 11.4 | Moderate expression |
| A549 (lung carcinoma) | 9.8 | Moderate expression |
| HCT116 (colorectal carcinoma) | 7.3 | Low expression |
| K562 (leukemia) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1195C>T (p.Arg399*) | Nonsense | <0.1% | Loss of function; associated with MCPH10 |
| c.2077G>A (p.Glu693Lys) | Missense | <0.1% | Unknown significance; reported in COSMIC |
| c.4285C>T (p.Arg1429Cys) | Missense | <0.1% | Unknown significance; reported in COSMIC |
| c.5125G>A (p.Gly1709Arg) | Missense | <0.1% | Unknown significance; reported in COSMIC |
| c.6022C>T (p.Arg2008Trp) | Missense | <0.1% | Unknown significance; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift) cause MCPH10 and impair MMEJ, leading to genomic instability.
Gain of Function (GOF)
Overexpression of wild-type POLQ in tumors is considered a gain-of-function in the context of cancer, promoting error-prone repair and mutagenesis.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, certain missense variants may interfere with polymerase or helicase activity.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding (GO:0003677) | • DNA-directed DNA polymerase activity (GO:0003887) |
| • DNA helicase activity (GO:0004386) | • DNA repair (GO:0006281) |
| • DNA replication (GO:0006260) | • Microhomology-mediated end joining (GO:1990392) |
| • Translesion synthesis (GO:0019985) | • Nucleus (GO:0005634) |
Pathways
• Microhomology-mediated end joining (MMEJ)
• Translesion synthesis (TLS)
• Base excision repair (BER)
• Double-strand break repair via alternative nonhomologous end joining (alt-NHEJ)
• DNA polymerase theta (Pol θ) is a 2590-amino acid protein with an N-terminal superfamily 2 helicase domain and a C-terminal A-family DNA polymerase domain. It is the key enzyme for microhomology-mediated end joining (MMEJ)
• a mutagenic double-strand break repair pathway. Pol θ can bypass DNA lesions via translesion synthesis and participates in base excision repair. Its expression is low in normal tissues but elevated in many cancers
• where it promotes survival and resistance to therapy. POLQ is a synthetic lethal target in BRCA1/2-deficient tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POLQ Knockout HEK293 Cell Line | EDC90479 | Human | 10721 | Details Get a Quote |
| POLQ Knockout HeLa Cell Line | EDJ-KQ32029 | Human | 10721 | Details Get a Quote |
| POLQ Knockout HCT 116 Cell Line | EDJ-KQ30651 | Human | 10721 | Details Get a Quote |
| POLQ Knockout A-549 Cell Line | EDJ-KQ63957 | Human | 10721 | Details Get a Quote |
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