TOPBP1: A Key Regulator of DNA Replication and Damage Response
Comprehensive gene overview of TOPBP1, including function, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | TOPBP1 |
|---|---|
| Full Name | DNA topoisomerase II binding protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q22.1 |
| NCBI Gene ID | 11073 ncbi.nlm.nih.gov/gene/11073 |
| Ensembl ID | ENSG00000163781 |
| UniProt ID | Q92547 |
| OMIM ID | 607760 |
| HGNC ID | 11998 |
| Aliases | TOP2BP1, MEC3, Dpb11 |
Description
TOPBP1 (DNA topoisomerase II binding protein 1) is a scaffold protein essential for DNA replication initiation and the DNA damage response. It activates the ATR kinase in response to replication stress and DNA damage, and participates in checkpoint signaling, DNA repair, and cell cycle control. TOPBP1 contains multiple BRCT domains that mediate protein-protein interactions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | TOPBP1 overexpression and mutations contribute to genomic instability and tumor progression. | COSMIC, ClinVar |
| Ovarian cancer | Altered TOPBP1 expression correlates with poor prognosis and chemoresistance. | COSMIC, ClinVar |
| Lung cancer | Somatic mutations in TOPBP1 are associated with DNA repair defects. | COSMIC |
| Colorectal cancer | TOPBP1 amplification and overexpression linked to tumorigenesis. | COSMIC |
| Primary microcephaly | Biallelic loss-of-function variants in TOPBP1 cause autosomal recessive primary microcephaly. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone marrow | 18.2 | Medium |
| Lymph node | 15.7 | Medium |
| Brain | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.1 | Cervical cancer cell line |
| MCF7 | 19.8 | Breast cancer cell line |
| A549 | 17.4 | Lung cancer cell line |
| K562 | 14.6 | Leukemia cell line |
| HEK293 | 12.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2960G>A (p.Arg987Gln) | Missense | 0.02% | Alters BRCT domain; potential loss of function |
| c.4135C>T (p.Arg1379Trp) | Missense | 0.01% | Impairs ATR activation |
| c.1234del (p.Glu412fs) | Frameshift | 0.005% | Loss of function; associated with microcephaly |
| c.1789A>G (p.Ile597Val) | Missense | 0.03% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt BRCT domains lead to loss of function, impairing DNA replication and damage signaling.
Gain of Function (GOF)
Amplification or overexpression of TOPBP1 in cancers may confer gain-of-function by enhancing ATR signaling and promoting cell survival under replication stress.
Dominant Negative (DN)
Missense mutations in BRCT domains can produce dominant-negative effects by interfering with wild-type TOPBP1 interactions, disrupting checkpoint activation.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication origin binding | • DNA damage response |
| • signal transduction by p53 class mediator | • protein binding |
| • ATR activation | • cell cycle checkpoint |
Pathways
• ATR signaling pathway
• DNA replication initiation
• Cell cycle checkpoints
• Homologous recombination repair
Protein Summary
TOPBP1 is a 1522-amino acid nuclear protein containing nine BRCT domains. It acts as a scaffold to recruit and activate ATR at sites of DNA damage or replication stress. TOPBP1 interacts with multiple proteins including RAD9, MDC1, and PCNA to coordinate checkpoint signaling and DNA repair. Its expression is cell cycle-regulated, peaking in S phase.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOPBP1 (p.T1105A) Point Mutation in HCT 116 Cell Line | EDC03192 | Human | 11073 | Details Get a Quote |
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