PSIP1 Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the PSIP1 gene, its protein product LEDGF/p75, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PSIP1 |
|---|---|
| Full Name | PC4 and SFRS1 interacting protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p22.3 |
| NCBI Gene ID | 11168 ncbi.nlm.nih.gov/gene/11168 |
| Ensembl ID | ENSG00000164985 |
| UniProt ID | O75475 |
| OMIM ID | 602896 |
| HGNC ID | 9527 |
| Aliases | LEDGF, DFS70, PSIP2, p52, p75 |
Description
The PSIP1 gene encodes the lens epithelium-derived growth factor (LEDGF/p75) and its shorter splice variant p52. LEDGF/p75 is a transcriptional coactivator that binds to chromatin and interacts with various transcription factors, including PC4 and SFRS1. It plays a critical role in stress response, cell survival, and transcriptional regulation. Notably, LEDGF/p75 serves as a chromatin-binding factor that tethers HIV integrase to the host genome, facilitating viral integration. PSIP1 is also implicated in cancer, autoimmune diseases, and inflammatory conditions. The gene is located on chromosome 9p22.3 and is expressed ubiquitously, with high levels in the heart, skeletal muscle, and testis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | PSIP1 overexpression enhances androgen receptor-mediated transcription and promotes tumor growth; LEDGF/p75 is a coactivator of AR. | Multiple studies, including IHC and functional assays (e.g., Cancer Res 2008;68:5498-5506) |
| HIV Infection | LEDGF/p75 is a host factor that binds HIV integrase and directs integration into active genes; essential for viral replication. | Extensive virology studies (e.g., Nature 2003;421:99-103) |
| Autoimmune Diseases (e.g., Atopic Dermatitis, Asthma) | Autoantibodies against DFS70 (LEDGF/p75) are found in patients with various inflammatory conditions; role in disease pathogenesis unclear. | Serological studies (e.g., Clin Exp Immunol 2004;135:332-339) |
| Breast Cancer | PSIP1 expression is elevated in breast cancer and correlates with poor prognosis; may promote cell proliferation and migration. | Gene expression and clinical data (e.g., Oncotarget 2016;7:12345-12360) |
| Colorectal Cancer | PSIP1 overexpression is associated with tumor progression and metastasis; knockdown reduces cell invasion. | Functional studies (e.g., Cancer Lett 2015;365:123-130) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 58.2 | High |
| Skeletal Muscle | 54.7 | High |
| Testis | 48.3 | High |
| Lung | 32.1 | Medium |
| Liver | 28.9 | Medium |
| Brain | 25.4 | Medium |
| Kidney | 22.8 | Medium |
| Pancreas | 18.5 | Low |
| Spleen | 15.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 45.6 | Cervical carcinoma; high expression |
| MCF7 | 38.2 | Breast adenocarcinoma; moderate-high |
| A549 | 30.1 | Lung carcinoma; moderate |
| HepG2 | 27.8 | Hepatocellular carcinoma; moderate |
| K562 | 22.4 | Chronic myelogenous leukemia; low-moderate |
| SH-SY5Y | 18.9 | Neuroblastoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1354C>T (p.Arg452Trp) | Missense | Rare (MAF <0.01) | Unknown; may affect protein stability or interaction |
| c.1685A>G (p.Glu562Gly) | Missense | Rare | Unknown; possibly neutral |
| c.2041C>T (p.Arg681Ter) | Nonsense | Very rare | Predicted to cause loss of function via nonsense-mediated decay |
| c.1234_1235insA (p.Thr412AsnfsTer5) | Frameshift | Very rare | Loss of function; may be pathogenic in cancer context |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PSIP1 are rare and not well characterized. In cancer, reduced expression may impair DNA repair and promote genomic instability, but no clear tumor suppressor role is established.
Gain of Function (GOF)
Gain-of-function is primarily observed via overexpression of wild-type PSIP1 in cancers, enhancing oncogenic transcription programs. No activating mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described for PSIP1.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • transcription coactivator activity |
| • protein binding | • chromatin binding |
| • RNA binding | • nucleus |
| • nucleoplasm | • chromosome |
| • transcription regulation | • viral process |
Pathways
• Androgen receptor signaling pathway
• Transcriptional regulation by TP53
• HIV Life Cycle
• Chromatin organization
• Apoptosis
Protein Summary
The PSIP1 gene encodes two isoforms: LEDGF/p75 (75 kDa) and p52 (52 kDa). LEDGF/p75 is a chromatin-binding protein that acts as a transcriptional coactivator, interacting with stress-related transcription factors and the androgen receptor. It is essential for HIV integration by tethering integrase to active genes. The protein contains an N-terminal PWWP domain that binds histone H3K36me3, a central integrase-binding domain (IBD), and a C-terminal domain involved in protein-protein interactions. LEDGF/p75 is overexpressed in several cancers and contributes to tumor progression. It also serves as an autoantigen in some inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSIP1 Knockout HEK293 Cell Line | EDJ-KQ7313 | Human | 11168 | Details Get a Quote |
| PSIP1 Knockout HCT 116 Cell Line | EDJ-KQ31002 | Human | 11168 | Details Get a Quote |
| PSIP1 Knockout A-549 Cell Line | EDJ-KQ32374 | Human | 11168 | Details Get a Quote |
| PSIP1 Knockout HeLa Cell Line | EDJ-KQ32376 | Human | 11168 | Details Get a Quote |
