POLD4 Gene: DNA Polymerase Delta Subunit 4 - Structure, Function, and Clinical Significance
A comprehensive biomedical overview of POLD4, encoding the smallest subunit of DNA polymerase delta, essential for DNA replication and repair, with implications in cancer and genetic disorders.
Gene Information Card
| Symbol | POLD4 |
|---|---|
| Full Name | DNA polymerase delta 4, accessory subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 57804 ncbi.nlm.nih.gov/gene/57804 |
| Ensembl ID | ENSG00000175455 |
| UniProt ID | Q9HCU8 |
| OMIM ID | 611525 |
| HGNC ID | 17918 |
| Aliases | p12, POLDS, DNA polymerase delta subunit p12 |
Description
POLD4 encodes the p12 subunit of DNA polymerase delta, a heterotetrameric enzyme essential for eukaryotic DNA replication and repair. The p12 subunit is critical for the stability of the polymerase delta complex and modulates its activity. POLD4 is involved in DNA replication, DNA damage response, and base excision repair. Alterations in POLD4 expression or mutations have been linked to various cancers and genetic disorders, highlighting its clinical relevance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered POLD4 expression or mutations may affect DNA replication fidelity and repair, contributing to genomic instability and tumorigenesis. | COSMIC database lists POLD4 mutations in multiple cancer types; studies show reduced POLD4 expression in some tumors. |
| Immunodeficiency (potential) | Defects in DNA polymerase delta subunits can impair V(D)J recombination and immune cell development. | Inferred from functional homology; direct evidence limited. |
| Developmental disorders | Mutations affecting polymerase delta function may lead to replication stress and developmental abnormalities. | ClinVar reports variants of uncertain significance; no confirmed OMIM phenotype. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.4 | Medium |
| Bone marrow | 8.7 | Low |
| Lymph node | 7.9 | Low |
| Spleen | 7.5 | Low |
| Brain | 5.2 | Low |
| Liver | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 | 10.5 | Leukemia cell line; moderate expression |
| HeLa | 9.8 | Cervical carcinoma; moderate expression |
| A549 | 8.9 | Lung carcinoma; moderate expression |
| MCF7 | 7.6 | Breast adenocarcinoma; low expression |
| HEK 293 | 6.4 | Embryonic kidney; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of start codon; may affect protein expression |
| c.157C>T (p.Arg53Cys) | Missense | Rare | Located in conserved region; may affect subunit interaction |
| c.238_239del (p.Leu80fs) | Frameshift | Rare | Predicted to cause premature truncation; likely loss of function |
| c.331G>A (p.Ala111Thr) | Missense | Rare | In C-terminal region; may affect DNA binding |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein likely result in loss of function, impairing polymerase delta complex stability and activity.
Gain of Function (GOF)
No evidence of gain-of-function mutations; POLD4 is not known to have oncogenic gain-of-function variants.
Dominant Negative (DN)
Missense mutations in critical domains may exert dominant-negative effects by disrupting the polymerase delta complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • DNA-directed DNA polymerase activity |
| • protein binding | • nucleus |
| • DNA replication | • DNA repair |
| • base-excision repair | • DNA damage response |
Pathways
• DNA replication
• Base excision repair
• Mismatch repair
• Fanconi anemia pathway
• Cell cycle checkpoints
Protein Summary
The POLD4 protein, also known as p12, is a 12 kDa subunit of DNA polymerase delta. It is essential for the stability of the polymerase delta holoenzyme and modulates its processivity and fidelity. p12 is degraded upon DNA damage, leading to the conversion of the tetrameric polymerase delta to a trimeric form, which alters the enzyme's activity in DNA repair. POLD4 is predominantly expressed in tissues with high proliferative capacity, such as testis and bone marrow. Its expression is regulated during the cell cycle and in response to genotoxic stress. Mutations in POLD4 are rare but have been identified in various cancers, suggesting a potential role in tumor suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POLD4 Knockout HEK293 Cell Line | EDJ-KQ51592 | Human | 57804 | Details Get a Quote |
| POLD4 Knockout HeLa Cell Line | EDJ-KQ56918 | Human | 57804 | Details Get a Quote |
| POLD4 Knockout A-549 Cell Line | EDJ-KQ65426 | Human | 57804 | Details Get a Quote |
| POLD4 Knockout HCT 116 Cell Line | EDJ-KQ73863 | Human | 57804 | Details Get a Quote |
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