POLQ
protein-codingDNA polymerase theta, the group of DNA polymerases
Gene summary
Enables several functions, including catalytic activity, acting on DNA; identical protein binding activity; and magnesium ion binding activity. Involved in DNA metabolic process; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in nucleoplasm. Is active in mitochondrial nucleoid; nucleus; and site of double-strand break. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
NM_199420.4
Inheritance
—
ClinVar variants
U:2459B:1200
Top phenotype
POLQ-related disorder
gnomAD constraint
pLI —, LoF o/e 1.05
Max pathogenic AF
—
Genomic locus
chr3:121,431,431-121,545,988
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~114.6 kbLoading mutation effect viewer...
GenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to POLQ variants in ClinVar
not specifiedTotal: 3599
POLQ-related disorderTotal: 61
not providedTotal: 39
Familial cancer of breastTotal: 5
TeratomaTotal: 1
Hereditary breast ovarian cancer syndromeTotal: 1
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199420.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 1069 | 5 | 1079 | ||
| missense | 2447 | 112 | 13 | 2572 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 2459 | 1182 | 18 | 3659 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 15 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_955452.3 | 30 | MANE Select | |
| Ensembl | ENSP00000264233.5 | 30 | MANE Select | |
| Ensembl | ENSP00000507534.1 | 2 | Standard | |
| Ensembl | ENSP00000603010.1 | 30 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HDR through MMEJ (alt-NHEJ)
- DNA Repair
- DNA Double-Strand Break Repair
- Homology Directed Repair
- Purine metabolism
Biological Process
- double-strand break repair via homologous recombination
- DNA-dependent DNA replication
- DNA repair
- base-excision repair
- double-strand break repair
Molecular Function
- chromatin binding
- damaged DNA binding
- DNA-directed DNA polymerase activity
- protein binding
- ATP binding
Cellular Component
- nucleus
- nucleoplasm
- chromosome
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264233
- Coding exons
- 30
- Length
- 114576
- Individuals with no LoFs
- 125208
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 538
- Defined
- 125748
- p
- 0.00215
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.751 | 1249 | 1.33e+3 | 0.942 | 0.0000662 | 17014 |
| Missense (PolyPhen) | 365 | 425.09 | 0.85864 | 5457 | ||
| Synonymous | 0.817 | 440 | 462 | 0.952 | 0.0000221 | 4932 |
| Loss of Function | -0.452 | 122 | 117 | 1.05 | 0.00000666 | 1444 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0035 | 0.0034 | notable |
| Latino/Admixed American | 0.0023 | 0.0023 | notable |
| Ashkenazi Jewish | 0.00050 | 0.00040 | rare |
| East Asian | 0.0037 | 0.0034 | notable |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.0017 | 0.0017 | notable |
| South Asian | 0.0044 | 0.0043 | notable |
| Other | 0.0023 | 0.0023 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA polymerase that promotes microhomology-mediated end- joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery triggered in response to double-strand breaks in DNA (PubMed:25642963, PubMed:25643323). MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation (PubMed:25642963, PubMed:25643323). POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). POLQ-mediated MMEJ may be required to promote the survival of cells with a compromised HR repair pathway, thereby preventing genomic havoc by resolving unrepaired lesions (By similarity). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs. It then extends each strand from the base-paired region using the opposing overhang as a template. Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ (PubMed:25643323). The polymerase activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). Also exhibits low-fidelity DNA synthesis, translesion synthesis and lyase activity, and it is implicated in interstrand-cross-link repair, base excision repair and DNA end-joining (PubMed:14576298, PubMed:18503084, PubMed:19188258, PubMed:24648516). Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs (By similarity). {ECO:0000250|UniProtKB:Q8CGS6, ECO:0000269|PubMed:14576298, ECO:0000269|PubMed:18503084, ECO:0000269|PubMed:19188258, ECO:0000269|PubMed:21050863, ECO:0000269|PubMed:22135286, ECO:0000269|PubMed:24648516, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:25643323}.;
- Disease
- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:20624954, ECO:0000269|PubMed:20700469, ECO:0000269|PubMed:25409685}. Note=The gene represented in this entry may be involved in disease pathogenesis.;
Recessive Scores
- pRec
- 0.0939
Intolerance Scores
- LoFtool
- 0.648
- RVIS EVS
- 2.32
- RVIS percentile EVS
- 98.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.786
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |