PSTPIP1 Gene (Proline-Serine-Threonine Phosphatase Interacting Protein 1)
Key regulator of cytoskeletal dynamics and immune cell signaling; mutations cause PAPA syndrome and related autoinflammatory disorders.
Gene Information Card
| Symbol | PSTPIP1 |
|---|---|
| Full Name | Proline-Serine-Threonine Phosphatase Interacting Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q24.3 |
| NCBI Gene ID | 9051 ncbi.nlm.nih.gov/gene/9051 |
| Ensembl ID | ENSG00000140368 |
| UniProt ID | O43586 |
| OMIM ID | 606347 |
| HGNC ID | 9580 |
| Aliases | CD2BP1, CD2-binding protein 1, PSTPIP, proline-serine-threonine phosphatase-interacting protein 1 |
Description
PSTPIP1 encodes the proline-serine-threonine phosphatase interacting protein 1, a cytoskeletal adaptor protein that binds to PTPN12 (PTP-PEST) and CD2. It regulates actin polymerization, T-cell activation, and inflammasome assembly. Mutations in PSTPIP1 cause PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, acne) and are associated with other autoinflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| PAPA syndrome (Pyogenic Arthritis, Pyoderma Gangrenosum, Acne) | Gain-of-function mutations (e.g., A230T, E250Q) enhance PSTPIP1 binding to pyrin, leading to increased IL-1β production and inflammasome activation. | OMIM #604416; multiple case reports in ClinVar and literature. |
| Pyoderma gangrenosum (isolated) | Same PSTPIP1 mutations as PAPA; aberrant pyrin inflammasome signaling. | ClinVar; case studies. |
| Acne fulminans | Overlap with PAPA; PSTPIP1 variants may predispose to severe inflammatory acne. | OMIM; case reports. |
| Hyperzincemia / hypercalprotectinemia | Elevated S100A8/A9 (calprotectin) due to inflammasome dysregulation; PSTPIP1 mutations reported. | ClinVar; literature. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Lung | 8.1 | Medium |
| Bone marrow | 7.9 | Medium |
| Lymph node | 7.5 | Medium |
| Brain | 2.3 | Low |
| Heart | 1.8 | Low |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 15.0 | High expression; used in inflammasome studies. |
| K-562 (lymphoblast) | 12.3 | Moderate expression. |
| HeLa (cervical carcinoma) | 4.5 | Low expression. |
| HEK293 (embryonic kidney) | 3.2 | Low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.688G>A (p.Ala230Thr) | Missense | ~50% of PAPA cases | Gain-of-function; increases pyrin binding and IL-1β secretion. |
| c.748G>C (p.Glu250Gln) | Missense | ~30% of PAPA cases | Gain-of-function; similar mechanism to A230T. |
| c.773C>T (p.Thr258Met) | Missense | Rare | Likely gain-of-function; reported in PAPA. |
| c.764A>G (p.Asp255Gly) | Missense | Rare | Gain-of-function; associated with PAPA. |
| c.374C>T (p.Thr125Met) | Missense | Rare | Uncertain significance; reported in autoinflammatory context. |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in disease; knockout studies in mice show mild immune defects.
Gain of Function (GOF)
Dominant; A230T, E250Q, D255G, T258M enhance PSTPIP1-pyrin interaction, leading to constitutive inflammasome activation and IL-1β overproduction.
Dominant Negative (DN)
Not described for PSTPIP1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pyrin inflammasome pathway (Reactome: R-HSA-844456)
• CD2-mediated T-cell activation (Reactome: R-HSA-202430)
• Regulation of actin dynamics for phagocytic cup formation (Reactome: R-HSA-2029482)
Protein Summary
PSTPIP1 is a 416-amino acid cytosolic adaptor protein containing a F-BAR domain that mediates membrane curvature and actin binding. It interacts with PTPN12 (PTP-PEST) via a coiled-coil region and with CD2 via its SH3 domain. The protein also binds pyrin (MEFV) and WASP, linking cytoskeletal regulation to inflammasome signaling. Mutations cluster in the coiled-coil domain and enhance pyrin binding, causing IL-1β-driven autoinflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSTPIP1 Knockout HEK293 Cell Line | EDJ-KQ6444 | Human | 9051 | Details Get a Quote |
| PSTPIP1 Knockout HeLa Cell Line | EDJ-KQ55066 | Human | 9051 | Details Get a Quote |
| PSTPIP1 Knockout A-549 Cell Line | EDJ-KQ63548 | Human | 9051 | Details Get a Quote |
| PSTPIP1 Knockout HCT 116 Cell Line | EDJ-KQ72016 | Human | 9051 | Details Get a Quote |
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