PIAS1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the PIAS1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PIAS1 |
|---|---|
| Full Name | protein inhibitor of activated STAT1 |
| Gene Type | protein coding |
| Chromosomal Location | 15q23 |
| NCBI Gene ID | 8554 ncbi.nlm.nih.gov/gene/8554 |
| Ensembl ID | ENSG00000033800 |
| UniProt ID | O75925 |
| OMIM ID | 603566 |
| HGNC ID | 17002 |
| Aliases | DDXBP1, GU/RH-II, ZMIZ4, ARIP3, Pias1 |
Description
The PIAS1 gene encodes a protein inhibitor of activated STAT1, a member of the PIAS family of E3 SUMO ligases. PIAS1 modulates various cellular processes including transcription, DNA repair, and immune response by SUMOylating target proteins and inhibiting STAT1-mediated gene expression. It is involved in multiple signaling pathways and has been implicated in cancer, inflammatory diseases, and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | PIAS1 overexpression enhances androgen receptor signaling and promotes tumor growth. | PMID: 14517278; COSMIC |
| Breast Cancer | PIAS1 regulates estrogen receptor activity and may contribute to endocrine resistance. | PMID: 19029910; COSMIC |
| Inflammatory Diseases | PIAS1 modulates NF-kB and STAT1 signaling, affecting inflammatory responses. | PMID: 15123770; ClinVar |
| Infectious Diseases | PIAS1 inhibits STAT1-mediated antiviral responses, impacting viral pathogenesis. | PMID: 15123770; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 31.2 | High |
| Lymph node | 24.5 | High |
| Spleen | 22.1 | High |
| Bone marrow | 18.7 | Medium |
| Lung | 12.3 | Medium |
| Brain | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 28.4 | Cervical cancer cell line; high expression |
| MCF7 | 22.1 | Breast cancer cell line; moderate expression |
| A549 | 15.6 | Lung cancer cell line; moderate expression |
| HepG2 | 12.3 | Liver cancer cell line; low expression |
| K562 | 9.8 | Leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1099C>T (p.Arg367Trp) | Missense | 0.01% (gnomAD) | Loss of SUMO ligase activity; associated with developmental delay |
| c.1546A>G (p.Lys516Glu) | Missense | 0.005% (gnomAD) | Altered nuclear localization; potential gain-of-function in cancer |
| c.1780C>T (p.Arg594Ter) | Nonsense | Rare | Truncated protein; loss of function; observed in cancer samples (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the RING finger domain or catalytic activity impair SUMO ligase function, leading to reduced SUMOylation of substrates and altered gene regulation.
Gain of Function (GOF)
Some missense mutations may enhance PIAS1 stability or interaction with partners, leading to increased inhibition of STAT1 and enhanced oncogenic signaling.
Dominant Negative (DN)
Truncated or misfolded PIAS1 proteins can interfere with wild-type PIAS1 function by competing for substrate binding, thereby reducing overall SUMOylation activity.
View complete mutation data：
Gene Ontology (GO)
| • SUMO transferase activity | • protein SUMOylation |
| • transcription coregulator activity | • signal transducer activity |
| • nucleus | • cytoplasm |
| • DNA damage response | • negative regulation of transcription by RNA polymerase II |
Pathways
• SUMOylation pathway
• JAK-STAT signaling pathway
• Androgen receptor signaling
• NF-kB signaling
• p53 signaling
Protein Summary
PIAS1 is a 650-amino acid protein with a conserved RING finger domain that confers E3 SUMO ligase activity. It contains an SAP domain for DNA binding and a PINIT domain for substrate recognition. PIAS1 primarily SUMOylates transcription factors such as p53, STAT1, and androgen receptor, modulating their activity. It also acts as a transcriptional corepressor by recruiting HDACs. PIAS1 is widely expressed and plays critical roles in immune regulation, cell proliferation, and stress responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIAS1 Knockout HEK293 Cell Line | EDJ-KQ515 | Human | 8554 | Details Get a Quote |
| PIAS1 Knockout HCT 116 Cell Line | EDJ-KQ18842 | Human | 8554 | Details Get a Quote |
| PIAS1 Knockout HeLa Cell Line | EDJ-KQ18843 | Human | 8554 | Details Get a Quote |
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