POLQ
Basic information
Region (hg38): 3:121431431-121545988
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
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.
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.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 922 | 930 | ||||
missense | 1960 | 90 | 26 | 2076 | ||
nonsense | 0 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 20 | 1 | 21 | |||
non coding | 0 | |||||
Total | 0 | 0 | 1960 | 1012 | 35 |
Variants in POLQ
This is a list of pathogenic ClinVar variants found in the POLQ region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
3-121432307-C-G | not specified | Likely benign (Sep 16, 2020) | ||
3-121432309-C-T | not specified | Uncertain significance (Feb 16, 2024) | ||
3-121432310-A-G | not specified | Likely benign (Jun 09, 2024) | ||
3-121432313-A-G | not specified | Likely benign (Sep 30, 2021) | ||
3-121432316-G-A | not specified | Likely benign (Sep 02, 2019) | ||
3-121432317-T-A | not specified | Uncertain significance (Apr 18, 2024) | ||
3-121432318-C-A | not specified | Uncertain significance (Sep 15, 2023) | ||
3-121432329-C-G | not specified | Uncertain significance (Apr 23, 2022) | ||
3-121432330-C-T | not specified | Uncertain significance (Nov 06, 2021) | ||
3-121432333-A-C | not specified | Uncertain significance (Aug 10, 2022) | ||
3-121432334-G-A | not specified | Likely benign (Feb 12, 2022) | ||
3-121432340-G-A | not specified | Likely benign (Jun 11, 2022) | ||
3-121432343-T-C | not specified | Uncertain significance (Sep 16, 2022) | ||
3-121432345-T-A | not specified | Uncertain significance (Jan 15, 2022) | ||
3-121432345-T-C | not specified | Uncertain significance (Mar 29, 2022) | ||
3-121432347-T-C | not specified | Uncertain significance (Mar 16, 2022) | ||
3-121432350-A-T | not specified | Uncertain significance (Dec 29, 2023) | ||
3-121432360-T-G | not specified | Uncertain significance (Jul 08, 2022) | ||
3-121432364-T-C | not specified | Likely benign (Jul 04, 2021) | ||
3-121432368-A-C | not specified | Uncertain significance (Jul 26, 2022) | ||
3-121432371-G-T | not specified | Uncertain significance (Apr 17, 2024) | ||
3-121432373-C-G | not specified | Likely benign (Oct 03, 2022) | ||
3-121432373-C-T | not specified | Likely benign (Aug 21, 2021) | ||
3-121432374-A-T | not specified | Uncertain significance (Feb 27, 2024) | ||
3-121432380-A-G | not specified | Uncertain significance (Apr 23, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
POLQ | protein_coding | protein_coding | ENST00000264233 | 30 | 114576 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.31e-82 | 6.07e-14 | 125208 | 2 | 538 | 125748 | 0.00215 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.751 | 1249 | 1.33e+3 | 0.942 | 0.0000662 | 17014 |
Missense in 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 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00583 | 0.00571 |
Ashkenazi Jewish | 0.000503 | 0.000397 |
East Asian | 0.00367 | 0.00343 |
Finnish | 0.000233 | 0.000231 |
European (Non-Finnish) | 0.00170 | 0.00168 |
Middle Eastern | 0.00367 | 0.00343 |
South Asian | 0.00436 | 0.00426 |
Other | 0.00230 | 0.00228 |
dbNSFP
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.;
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | High | Medium | High |
Primary Immunodeficiency | High | High | High |
Cancer | High | High | High |
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