POLE4
DNA polymerase epsilon 4, accessory subunit, the group of DNA polymerases
Basic information
Region (hg38): 2:74958642-74970128
Links
Phenotypes
GenCC
Source:
No genCC data.
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 POLE4 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 | 1 | |||||
| missense | 7 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 7 | 0 | 1 |
Variants in POLE4
This is a list of pathogenic ClinVar variants found in the POLE4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-74958692-G-C | not specified | Uncertain significance (Mar 23, 2022) | ||
| 2-74958692-G-T | not specified | Uncertain significance (Jun 13, 2024) | ||
| 2-74958705-G-A | not specified | Uncertain significance (Mar 23, 2022) | ||
| 2-74958710-A-T | not specified | Uncertain significance (May 06, 2024) | ||
| 2-74958770-A-G | not specified | Uncertain significance (Sep 17, 2021) | ||
| 2-74958771-C-A | not specified | Uncertain significance (Jun 24, 2022) | ||
| 2-74958788-C-T | not specified | Uncertain significance (Aug 30, 2021) | ||
| 2-74958847-G-A | Benign (Aug 07, 2018) | |||
| 2-74958870-T-C | not specified | Uncertain significance (Mar 20, 2024) | ||
| 2-74958874-C-G | not specified | Uncertain significance (Mar 04, 2024) | ||
| 2-74959378-G-T | not specified | Uncertain significance (Jun 10, 2022) | ||
| 2-74959407-C-G | not specified | Uncertain significance (Apr 01, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| POLE4 | protein_coding | protein_coding | ENST00000483063 | 4 | 11637 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000699 | 0.530 | 125474 | 0 | 2 | 125476 | 0.00000797 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.330 | 60 | 53.2 | 1.13 | 0.00000241 | 703 |
| Missense in Polyphen | 14 | 13.002 | 1.0768 | 195 | ||
| Synonymous | -0.413 | 24 | 21.6 | 1.11 | 0.00000104 | 241 |
| Loss of Function | 0.331 | 5 | 5.87 | 0.852 | 2.59e-7 | 70 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May play a role in allowing polymerase epsilon to carry out its replication and/or repair function.;
- Pathway
- Nucleotide excision repair - Homo sapiens (human);Pyrimidine metabolism - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Pyrimidine metabolism;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Purine metabolism;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA replication initiation;DNA Replication;Pyrimidine metabolism;Synthesis of DNA;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Telomere C-strand synthesis initiation;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;G1/S Transition;Recognition of DNA damage by PCNA-containing replication complex;DNA Replication Pre-Initiation;M/G1 Transition;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;HDR through Homologous Recombination (HRR)
(Consensus)
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- loftool
- 0.675
- rvis_EVS
- -0.01
- rvis_percentile_EVS
- 52.85
Haploinsufficiency Scores
- pHI
- 0.360
- hipred
- Y
- hipred_score
- 0.628
- ghis
- 0.441
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.839
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pole4
- Phenotype
- limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; pigmentation phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- G1/S transition of mitotic cell cycle;histone H3 acetylation;DNA biosynthetic process
- Cellular component
- nucleus;nucleoplasm;Ada2/Gcn5/Ada3 transcription activator complex;epsilon DNA polymerase complex
- Molecular function
- DNA binding;DNA-directed DNA polymerase activity;protein binding;protein heterodimerization activity