POLD1: DNA Polymerase Delta 1, Catalytic Subunit
Essential for DNA replication and repair; mutations linked to cancer and progeroid syndromes
Gene Information Card
| Symbol | POLD1 |
|---|---|
| Full Name | DNA Polymerase Delta 1, Catalytic Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 5424 ncbi.nlm.nih.gov/gene/5424 |
| Ensembl ID | ENSG00000162849 |
| UniProt ID | P28340 |
| OMIM ID | 174761 |
| HGNC ID | 9175 |
| Aliases | CDC2, CRCS10, MDPL, POLD |
Description
POLD1 encodes the catalytic subunit of DNA polymerase delta, an enzyme essential for nuclear DNA replication and repair. It possesses both DNA polymerase and 3'->5' exonuclease proofreading activities. Mutations in POLD1 are associated with predisposition to colorectal cancer, endometrial cancer, and mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer, hereditary nonpolyposis, type 10 | Defective DNA replication fidelity due to exonuclease domain mutations leads to increased mutation rate | PMID: 23431114, ClinVar |
| Endometrial cancer | Similar mechanism as colorectal cancer; POLD1 mutations increase genomic instability | PMID: 23431114, ClinVar |
| Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) | Missense mutations in the polymerase domain impair DNA replication and cause premature aging | PMID: 20601937, OMIM #615381 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 27.8 | High |
| Bone marrow | 18.5 | Medium |
| Lymph node | 15.2 | Medium |
| Brain | 10.1 | Medium |
| Liver | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.4 | Cervical cancer cell line |
| K562 | 19.7 | Leukemia cell line |
| HEK293 | 16.3 | Embryonic kidney cell line |
| HepG2 | 12.1 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Leu474Pro | Missense | <0.01% | Associated with MDPL syndrome; reduces polymerase activity |
| p.Ser478Asn | Missense | <0.01% | Associated with MDPL syndrome; impairs DNA replication |
| p.Asp316Gly | Missense | <0.01% | Exonuclease domain; linked to colorectal cancer predisposition |
| p.Arg689Trp | Missense | <0.01% | Exonuclease domain; linked to endometrial cancer |
Mutation functional classification
Loss of Function (LOF)
Exonuclease domain mutations (e.g., p.Asp316Gly) reduce proofreading activity, leading to increased mutation rate and cancer predisposition.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
MDPL-associated mutations (e.g., p.Leu474Pro) are thought to exert dominant-negative effects by disrupting polymerase complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • DNA polymerase activity | • 3'-5' exonuclease activity |
| • nucleus | • protein binding |
Pathways
• DNA replication
• Mismatch repair
• Base excision repair
• Nucleotide excision repair
Protein Summary
The POLD1 protein (1247 amino acids) contains an N-terminal exonuclease domain for proofreading and a C-terminal polymerase domain. It functions as part of the DNA polymerase delta holoenzyme, which includes the accessory subunits POLD2, POLD3, and POLD4. The enzyme is critical for lagging strand synthesis during DNA replication and participates in various DNA repair pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APOLD1 Knockout HEK293 Cell Line | EDJ-KQ8938 | Human | 81575 | Details Get a Quote |
| APOLD1 Knockout HCT 116 Cell Line | EDJ-KQ36523 | Human | 81575 | Details Get a Quote |
| APOLD1 Knockout HeLa Cell Line | EDJ-KQ36524 | Human | 81575 | Details Get a Quote |
| APOLD1 Knockout A-549 Cell Line | EDJ-KQ65903 | Human | 81575 | Details Get a Quote |
| pold1 (p.G176R) Point Mutation in MB49-GFP Cell Line | EDC03015 | 18971 | Details Get a Quote |
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