SLFN11 (Schlafen Family Member 11): A Key Determinant of DNA Damage Response and Chemosensitivity
Explore the genomic structure, expression, mutations, and clinical significance of SLFN11, a pivotal gene in cancer therapy response and replication stress.
Gene Information Card
| Symbol | SLFN11 |
|---|---|
| Full Name | Schlafen family member 11 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 91607 ncbi.nlm.nih.gov/gene/91607 |
| Ensembl ID | ENSG00000172057 |
| UniProt ID | Q7Z7L1 |
| OMIM ID | 614953 |
| HGNC ID | 26633 |
| Aliases | SLFN11, Schlafen 11, FLJ20637 |
Description
SLFN11 (Schlafen family member 11) is a protein-coding gene located on chromosome 17q12. It belongs to the Schlafen family, which is involved in various cellular processes including growth regulation, immune response, and DNA damage response. SLFN11 has gained significant attention due to its role as a major determinant of sensitivity to DNA-damaging chemotherapeutic agents, such as cisplatin, etoposide, and topoisomerase inhibitors. It functions by binding to replication forks and inducing replication stress, leading to cell cycle arrest and apoptosis in response to DNA damage. SLFN11 is frequently inactivated in many cancer types, often through epigenetic silencing or copy number loss, making it a promising biomarker for predicting therapy response and a potential target for therapeutic intervention.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Loss of SLFN11 expression leads to resistance to DNA-damaging agents; its presence enhances chemosensitivity by promoting replication stress and apoptosis. | High-throughput screening and clinical studies (e.g., Reinhold et al., 2015; Zoppoli et al., 2012) |
| Small cell lung cancer (SCLC) | SLFN11 expression is frequently lost in SCLC, correlating with resistance to platinum-based chemotherapy. | Clinical studies (e.g., Pietanza et al., 2018) |
| Ovarian cancer | Low SLFN11 expression is associated with poor response to platinum-based therapy. | Clinical studies (e.g., Kang et al., 2018) |
| Colorectal cancer | SLFN11 methylation and silencing contribute to resistance to irinotecan and other topoisomerase inhibitors. | Preclinical studies (e.g., Deng et al., 2017) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 10.2 | Low |
| Lymph node | 8.5 | Low |
| Spleen | 7.8 | Low |
| Thymus | 6.9 | Low |
| Lung | 4.3 | Low |
| Ovary | 3.1 | Low |
| Testis | 2.5 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung cancer) | 0.5 | Low expression; resistant to DNA damage |
| MCF7 (Breast cancer) | 2.3 | Moderate expression; partial sensitivity |
| HCT116 (Colorectal cancer) | 1.8 | Low expression; resistant to topoisomerase inhibitors |
| U2OS (Osteosarcoma) | 5.6 | High expression; sensitive to DNA damage |
| HEK293 (Embryonic kidney) | 3.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (<0.1%) | Potential loss of function; affects start codon |
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare (<0.1%) | Truncated protein; loss of function |
| c.456_457insA (p.Glu153fs) | Frameshift | Rare (<0.1%) | Frameshift; loss of function |
| Copy number loss | CNV | Frequent in cancer (e.g., 20-30% in SCLC) | Reduced expression; chemoresistance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) or epigenetic silencing lead to reduced SLFN11 protein levels, impairing its ability to induce replication stress and apoptosis, thereby conferring resistance to DNA-damaging agents.
Gain of Function (GOF)
Gain-of-function mutations are rare and not well-documented; overexpression of wild-type SLFN11 enhances chemosensitivity.
Dominant Negative (DN)
No dominant-negative mutations have been reported; however, truncated forms could potentially interfere with wild-type function, but evidence is lacking.
View complete mutation data：
Gene Ontology (GO)
| • DNA damage response | • Replication fork processing |
| • Cell cycle arrest | • Apoptosis |
| • Endonuclease activity | • ATP binding |
| • Zinc ion binding |
Pathways
• DNA damage response (DDR)
• Replication stress response
• p53 signaling pathway
• Apoptosis signaling
Protein Summary
The SLFN11 protein is a member of the Schlafen family, characterized by the presence of an AAA domain and a helicase-like domain. It localizes to the nucleus and interacts with replication forks. Upon DNA damage, SLFN11 is recruited to chromatin and inhibits replication by promoting fork collapse, leading to cell cycle arrest and apoptosis. It also possesses single-stranded DNA endonuclease activity. SLFN11 expression is regulated by epigenetic mechanisms, and its loss is a common event in cancer, contributing to therapy resistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLFN11 Knockout HEK293 Cell Line | EDJ-KQ10755 | Human | 91607 | Details Get a Quote |
| SLFN11 Knockout A-549 Cell Line | EDC90633 | Human | 91607 | Details Get a Quote |
| SLFN11 Knockout HeLa Cell Line | EDJ-KQ38355 | Human | 91607 | Details Get a Quote |
| SLFN11 Knockout HCT 116 Cell Line | EDJ-KQ74724 | Human | 91607 | Details Get a Quote |
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