MDC1: Mediator of DNA Damage Checkpoint 1
Key regulator of the DNA damage response and genome stability
Gene Information Card
| Symbol | MDC1 |
|---|---|
| Full Name | Mediator of DNA Damage Checkpoint 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 9656 ncbi.nlm.nih.gov/gene/9656 |
| Ensembl ID | ENSG00000137337 |
| UniProt ID | Q14676 |
| OMIM ID | 605667 |
| HGNC ID | 6970 |
| Aliases | NFBD1, KIAA0170 |
Description
MDC1 (mediator of DNA damage checkpoint 1) encodes a nuclear protein that acts as a key scaffold in the DNA damage response (DDR). It contains an N-terminal FHA domain and tandem BRCT repeats, which mediate interactions with phosphorylated proteins such as γH2AX and ATM. MDC1 is essential for the recruitment and retention of DNA repair factors at sites of double-strand breaks, facilitating checkpoint activation and repair.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | MDC1 loss or reduced expression impairs DNA repair, leading to genomic instability and increased cancer risk. | PMID: 18264134 |
| Lung cancer | MDC1 downregulation correlates with poor prognosis and defective DDR signaling. | PMID: 21750548 |
| Colorectal cancer | MDC1 mutations or altered expression contribute to tumor progression via compromised checkpoint activation. | PMID: 23034409 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Bone marrow | 9.8 | Medium |
| Brain | 6.1 | Low |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| MCF7 | 11.5 | Breast cancer cell line |
| A549 | 9.0 | Lung cancer cell line |
| HEK293 | 8.7 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2119C>T (p.Arg707*) | Nonsense | <0.1% | Truncation, loss of BRCT domain, impaired DDR |
| c.2546A>G (p.Glu849Gly) | Missense | <0.1% | Altered BRCT domain, reduced ATM interaction |
| c.1234delA (p.Thr412fs) | Frameshift | <0.1% | Loss of function, genomic instability |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt key domains (FHA, BRCT) lead to loss of MDC1 function, impairing DNA damage signaling and repair.
Gain of Function (GOF)
No documented gain-of-function mutations for MDC1.
Dominant Negative (DN)
Some missense mutations in the BRCT domain may act in a dominant-negative manner by competing with wild-type MDC1 for binding sites, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ATM signaling pathway (Reactome: R-HSA-5693565)
• DNA double-strand break response (Reactome: R-HSA-5693606)
• p53-dependent G1 DNA damage response (Reactome: R-HSA-69580)
Protein Summary
MDC1 is a 2089-amino-acid nuclear protein with a molecular weight of approximately 226 kDa. It contains an N-terminal forkhead-associated (FHA) domain and two C-terminal BRCA1 C-terminal (BRCT) repeats. MDC1 functions as a scaffold that binds γH2AX via its BRCT domains and recruits ATM, MRN complex, and other DDR factors to sites of DNA double-strand breaks. It is essential for checkpoint activation, chromatin remodeling, and efficient DNA repair.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIMMDC1 Knockout HEK293 Cell Line | EDJ-KQ11025 | Human | 51300 | Details Get a Quote |
| TIMMDC1 Knockout HCT 116 Cell Line | EDJ-KQ38917 | Human | 51300 | Details Get a Quote |
| TIMMDC1 Knockout HeLa Cell Line | EDJ-KQ38918 | Human | 51300 | Details Get a Quote |
| TIMMDC1 Knockout A-549 Cell Line | EDJ-KQ38916 | Human | 51300 | Details Get a Quote |
| MDC1 Knockout HEK293 Cell Line | EDJ-KQ50890 | Human | 9656 | Details Get a Quote |
| MDC1 Knockout HeLa Cell Line | EDJ-KQ55219 | Human | 9656 | Details Get a Quote |
| MDC1 Knockout A-549 Cell Line | EDJ-KQ63701 | Human | 9656 | Details Get a Quote |
| MDC1 Knockout HCT 116 Cell Line | EDJ-KQ72162 | Human | 9656 | Details Get a Quote |
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