POLD4
DNA polymerase delta 4, accessory subunit, the group of DNA polymerases
Basic information
Region (hg38): 11:67350771-67356972
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 POLD4 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 | 0 | |||||
| missense | 3 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 3 | |||||
| Total | 0 | 0 | 5 | 1 | 0 |
Variants in POLD4
This is a list of pathogenic ClinVar variants found in the POLD4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-67352011-T-C | not specified | Uncertain significance (Mar 15, 2024) | ||
| 11-67352749-G-T | not specified | Uncertain significance (Dec 13, 2022) | ||
| 11-67352793-C-A | not specified | Uncertain significance (Sep 26, 2023) | ||
| 11-67353001-G-A | Likely benign (Jan 01, 2023) | |||
| 11-67353009-A-G | not specified | Uncertain significance (Aug 30, 2021) | ||
| 11-67353345-C-T | not specified | Uncertain significance (Sep 06, 2022) | ||
| 11-67353365-G-A | not specified | Uncertain significance (Oct 26, 2022) | ||
| 11-67353371-G-C | not specified | Uncertain significance (Mar 31, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| POLD4 | protein_coding | protein_coding | ENST00000312419 | 4 | 6196 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.145 | 0.786 | 125541 | 0 | 16 | 125557 | 0.0000637 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.427 | 51 | 60.3 | 0.845 | 0.00000321 | 665 |
| Missense in Polyphen | 16 | 20.675 | 0.7739 | 220 | ||
| Synonymous | 0.218 | 23 | 24.4 | 0.944 | 0.00000122 | 202 |
| Loss of Function | 1.48 | 2 | 5.85 | 0.342 | 2.49e-7 | 68 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000619 | 0.0000615 |
| Ashkenazi Jewish | 0.000329 | 0.000298 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000708 | 0.0000617 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000164 | 0.000163 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). Under conditions of DNA replication stress, required for the repair of broken replication forks through break- induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480). {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611}.;
- Pathway
- Nucleotide excision repair - Homo sapiens (human);Pyrimidine metabolism - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Homologous recombination - Homo sapiens (human);Homologous recombination;Pyrimidine metabolism;DNA Replication;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Polymerase switching on the C-strand of the telomere;Purine metabolism;DNA Replication;Pyrimidine metabolism;Polymerase switching;Leading Strand Synthesis;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;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;Removal of the Flap Intermediate from the C-strand;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Recognition of DNA damage by PCNA-containing replication complex;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;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha);HDR through Homologous Recombination (HRR)
(Consensus)
Recessive Scores
- pRec
- 0.0898
Intolerance Scores
- loftool
- 0.636
- rvis_EVS
- 0.19
- rvis_percentile_EVS
- 66.57
Haploinsufficiency Scores
- pHI
- 0.271
- hipred
- Y
- hipred_score
- 0.740
- ghis
- 0.459
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pold4
- Phenotype
Gene ontology
- Biological process
- telomere maintenance;DNA-dependent DNA replication;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, DNA gap filling;translesion synthesis;telomere maintenance via semi-conservative replication;nucleotide-excision repair, DNA incision;DNA damage response, detection of DNA damage
- Cellular component
- nucleus;nucleoplasm;nucleolus;mitochondrion;cytosol;delta DNA polymerase complex
- Molecular function
- DNA-directed DNA polymerase activity;protein binding