GeneBe

POLQ

DNA polymerase theta, the group of DNA polymerases

Basic information

Region (hg38): 3:121431431-121545988

Links

ENSG00000051341 ∙ NCBI:10721 ∙ OMIM:604419 ∙ HGNC:9186 ∙ Uniprot:O75417 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLQ gene.

  • not_specified (3586 variants)
  • POLQ-related_disorder (61 variants)
  • not_provided (39 variants)
  • Teratoma (1 variants)
  • Hereditary_breast_ovarian_cancer_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLQ gene is commonly pathogenic or not. These statistics are base on transcript: NM_000199420.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1069
clinvar
5
clinvar
 1074
missense
2426
clinvar
110
clinvar
13
clinvar
 2549
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
1
clinvar
 2
splice donor/acceptor (+/-2bp)
0
Total 0 0 2429 1180 18
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
POLQprotein_codingprotein_codingENST00000264233 30114576
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.31e-826.07e-1412520825381257480.00215
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.75112491.33e+30.9420.000066217014
Missense in Polyphen365425.090.858645457
Synonymous0.8174404620.9520.00002214932
Loss of Function-0.4521221171.050.000006661444

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.005830.00571
Ashkenazi Jewish0.0005030.000397
East Asian0.003670.00343
Finnish0.0002330.000231
European (Non-Finnish)0.001700.00168
Middle Eastern0.003670.00343
South Asian0.004360.00426
Other0.002300.00228

dbNSFP

Source: dbNSFP

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.;
Pathway
HDR through MMEJ (alt-NHEJ);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Purine metabolism;Pyrimidine metabolism (Consensus)

Recessive Scores

pRec
0.0939

Intolerance Scores

loftool
0.648
rvis_EVS
2.32
rvis_percentile_EVS
98.37

Haploinsufficiency Scores

pHI
0.177
hipred
N
hipred_score
0.144
ghis
0.398

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.786

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Polq
Phenotype
immune system phenotype; hematopoietic system phenotype; cellular phenotype;

Gene ontology

Biological process
double-strand break repair via homologous recombination;DNA-dependent DNA replication;DNA repair;base-excision repair;double-strand break repair;cellular response to DNA damage stimulus;somatic hypermutation of immunoglobulin genes;protein homooligomerization;DNA biosynthetic process;double-strand break repair via alternative nonhomologous end joining;negative regulation of double-strand break repair via homologous recombination
Cellular component
nucleus;nucleoplasm;chromosome;cytoplasm
Molecular function
chromatin binding;damaged DNA binding;DNA-directed DNA polymerase activity;protein binding;ATP binding;single-stranded DNA-dependent ATPase activity;5'-deoxyribose-5-phosphate lyase activity