SLX4 (FANCP): Structure-Specific Endonuclease Subunit and Fanconi Anemia Protein
A key regulator of DNA repair, homologous recombination, and interstrand crosslink resolution; mutations cause Fanconi anemia complementation group P and increase cancer susceptibility.
Gene Information Card
| Symbol | SLX4 |
|---|---|
| Full Name | SLX4 structure-specific endonuclease subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 84464 ncbi.nlm.nih.gov/gene/84464 |
| Ensembl ID | ENSG00000188827 |
| UniProt ID | Q8IY92 |
| OMIM ID | 613278 |
| HGNC ID | 23845 |
| Aliases | FANCP, BTBD12, MUS312 |
Description
The SLX4 gene encodes a scaffolding protein that coordinates multiple structure-specific endonucleases, including MUS81-EME1, XPF-ERCC1, and SLX1, to resolve DNA repair intermediates such as Holliday junctions and interstrand crosslinks. It plays a critical role in homologous recombination, DNA damage response, and maintenance of genomic stability. Mutations in SLX4 cause Fanconi anemia complementation group P (FANCP), a rare genetic disorder characterized by bone marrow failure, developmental abnormalities, and cancer predisposition.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fanconi anemia complementation group P (FANCP) | Biallelic loss-of-function mutations impair DNA interstrand crosslink repair, leading to chromosomal instability and bone marrow failure. | OMIM #613951; ClinVar; PMID: 21131976 |
| Breast cancer | SLX4 mutations may increase susceptibility to breast cancer, though evidence is limited; likely due to defective DNA repair. | COSMIC; PMID: 23555315 |
| Other cancers | Somatic SLX4 alterations (mutations, copy number changes) are found in various tumors, contributing to genomic instability. | COSMIC; TCGA |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 30.2 | High |
| Bone marrow | 20.5 | Medium |
| Lymph node | 15.3 | Medium |
| Spleen | 12.8 | Medium |
| Liver | 8.1 | Low |
| Brain | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 25.0 | High expression; used in DNA repair studies |
| K562 (leukemia) | 18.2 | Moderate expression |
| MCF7 (breast cancer) | 12.5 | Moderate expression |
| A549 (lung cancer) | 10.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1210C>T (p.Arg404Ter) | Nonsense | Rare (found in FANCP families) | Loss of function; truncates protein, abolishing endonuclease scaffold activity |
| c.1745_1746del (p.Leu582fs) | Frameshift | Rare (found in FANCP) | Loss of function; premature termination |
| c.2170G>A (p.Gly724Arg) | Missense | Rare (found in FANCP) | Likely loss of function; disrupts protein-protein interactions |
| c.2482C>T (p.Arg828Trp) | Missense | Rare (found in FANCP) | Likely loss of function; affects DNA binding |
Mutation functional classification
Loss of Function (LOF)
Most SLX4 mutations are loss-of-function, leading to defective interstrand crosslink repair and Fanconi anemia phenotype.
Gain of Function (GOF)
No gain-of-function mutations reported; SLX4 acts as a tumor suppressor.
Dominant Negative (DN)
Not reported; SLX4 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • DNA repair | • DNA damage response |
| • interstrand crosslink repair | • Holliday junction resolution |
| • endonuclease activity | • protein binding |
| • nucleus |
Pathways
• Fanconi anemia pathway
• Homologous recombination
• DNA damage response
• Nucleotide excision repair (via XPF-ERCC1)
Protein Summary
SLX4 is a 1834-amino acid protein that acts as a molecular scaffold, recruiting structure-specific endonucleases to sites of DNA damage. It contains UBZ4 ubiquitin-binding domain, MLR domain, and SAP domain, which mediate protein-protein and DNA interactions. SLX4 is essential for resolving DNA interstrand crosslinks and replication fork intermediates, thereby maintaining genome stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLX4IP Knockout HEK293 Cell Line | EDJ-KQ8422 | Human | 128710 | Details Get a Quote |
| SLX4 Knockout HEK293 Cell Line | EDJ-KQ17902 | Human | 84464 | Details Get a Quote |
| SLX4 Knockout HeLa Cell Line | EDJ-KQ21221 | Human | 84464 | Details Get a Quote |
| SLX4 Knockout A-549 Cell Line | EDJ-KQ22528 | Human | 84464 | Details Get a Quote |
| SLX4 Knockout HCT 116 Cell Line | EDJ-KQ22529 | Human | 84464 | Details Get a Quote |
| SLX4IP Knockout A-549 Cell Line | EDJ-KQ35752 | Human | 128710 | Details Get a Quote |
| SLX4IP Knockout HCT 116 Cell Line | EDJ-KQ35754 | Human | 128710 | Details Get a Quote |
| SLX4IP Knockout HeLa Cell Line | EDJ-KQ35755 | Human | 128710 | Details Get a Quote |
| SLX4 (p.R178I) Point Mutation in HAP1 Cell Line | EDC03606 | Human | 84464 | Details Get a Quote |
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