POLD3: DNA Polymerase Delta 3, Accessory Subunit
Essential component of the DNA polymerase delta complex involved in DNA replication and repair
Gene Information Card
| Symbol | POLD3 |
|---|---|
| Full Name | DNA Polymerase Delta 3, Accessory Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 10714 ncbi.nlm.nih.gov/gene/10714 |
| Ensembl ID | ENSG00000177570 |
| UniProt ID | Q15054 |
| OMIM ID | 611415 |
| HGNC ID | 9177 |
| Aliases | p66, POLD3, DNA polymerase delta subunit 3 |
Description
POLD3 encodes the 66 kDa accessory subunit of DNA polymerase delta, a heterotetrameric enzyme essential for DNA replication and repair. The POLD3 subunit stabilizes the polymerase complex and enhances processivity. It is involved in lagging strand synthesis, DNA damage bypass, and double-strand break repair via microhomology-mediated end joining (MMEJ).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Somatic mutations in POLD3 may impair DNA repair fidelity, leading to microsatellite instability and tumorigenesis. | PMID: 23542689 |
| Breast cancer | Overexpression of POLD3 has been observed in breast tumors, potentially driving genomic instability. | PMID: 29127259 |
| Immunodeficiency with hyper-IgM type 2 | Biallelic loss-of-function mutations in POLD3 cause a rare primary immunodeficiency with defective class-switch recombination. | PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Bone marrow | 8.2 | Medium |
| Lymph node | 7.1 | Medium |
| Brain | 4.3 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.8 | Embryonic kidney cell line |
| HeLa | 8.5 | Cervical cancer cell line |
| MCF7 | 7.2 | Breast cancer cell line |
| HCT116 | 6.9 | Colorectal cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1420C>T (p.Arg474*) | Nonsense | <0.1% | Loss of function; associated with immunodeficiency |
| c.1873G>A (p.Gly625Arg) | Missense | 0.2% | Impaired complex stability; reported in colorectal cancer |
| c.2444_2445insA (p.Asn815Lysfs*2) | Frameshift | <0.1% | Loss of function; immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt subunit interaction lead to loss of DNA polymerase delta activity.
Gain of Function (GOF)
Not well characterized; some missense variants may increase processivity but evidence is limited.
Dominant Negative (DN)
Missense mutations that retain interaction with other subunits but impair catalytic activity may act in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • DNA polymerase activity | • protein binding |
| • nucleus | • DNA-directed DNA polymerase activity |
Pathways
• DNA replication (KEGG: hsa03030)
• Base excision repair (KEGG: hsa03410)
• Mismatch repair (KEGG: hsa03430)
• Fanconi anemia pathway (KEGG: hsa03460)
Protein Summary
POLD3 is a 66 kDa accessory subunit of the DNA polymerase delta complex. It contains an N-terminal domain that interacts with the catalytic subunit POLD1 and a C-terminal region that binds PCNA. The protein enhances processivity and is required for efficient lagging strand synthesis and DNA repair. POLD3 also participates in microhomology-mediated end joining (MMEJ) during double-strand break repair.
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