SPI1 (PU.1) Gene: Role in Hematopoiesis and Disease
A comprehensive overview of the SPI1 gene, its protein product PU.1, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | SPI1 |
|---|---|
| Full Name | Spi-1 proto-oncogene |
| Gene Type | Protein coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 6688 ncbi.nlm.nih.gov/gene/6688 |
| Ensembl ID | ENSG00000066336 |
| UniProt ID | P17947 |
| OMIM ID | 165170 |
| HGNC ID | 11266 |
| Aliases | PU.1, OF, SFPI1, SPI-A |
Description
The SPI1 gene encodes PU.1, an ETS-domain transcription factor that is a master regulator of hematopoiesis. It controls the expression of genes involved in the development and function of myeloid and B-lymphoid cells. Dysregulation of SPI1 is implicated in various leukemias and other hematological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Altered SPI1 expression or mutations affecting PU.1 function disrupt myeloid differentiation, leading to leukemogenesis. | COSMIC, ClinVar, literature |
| B-Cell Acute Lymphoblastic Leukemia (B-ALL) | Reduced PU.1 activity impairs B-cell development and contributes to leukemic transformation. | COSMIC, literature |
| Chronic Myelomonocytic Leukemia (CMML) | SPI1 mutations or dysregulation are associated with aberrant monocytic proliferation. | COSMIC, literature |
| Myelodysplastic Syndromes (MDS) | SPI1 alterations may contribute to ineffective hematopoiesis and progression to AML. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Spleen | High | High |
| Lymph Node | High | High |
| Blood | Medium | Medium |
| Lung | Low | Low |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | High | Myeloid lineage |
| HL-60 (AML) | High | Promyelocytic |
| THP-1 (Monocytic leukemia) | High | Monocytic |
| Raji (Burkitt lymphoma) | Medium | B-cell |
| HeLa (Cervical carcinoma) | Low | Non-hematopoietic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.748C>T (p.Arg250Ter) | Nonsense | Rare | Loss of function, truncated protein |
| c.836A>G (p.Glu279Gly) | Missense | Rare | Altered DNA binding affinity |
| c.1054C>T (p.Arg352Trp) | Missense | Rare | Reduced transcriptional activity |
| Chromosomal rearrangements | Structural | Rare | Dysregulation of SPI1 expression |
Mutation functional classification
Loss of Function (LOF)
Most SPI1 mutations in leukemia are loss-of-function, impairing PU.1's ability to regulate target genes essential for myeloid/B-cell differentiation.
Gain of Function (GOF)
Gain-of-function mutations are uncommon but may increase PU.1 activity, potentially contributing to aberrant proliferation in some contexts.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type PU.1 function, though this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • sequence-specific DNA binding | • protein heterodimerization activity |
| • regulation of transcription by RNA polymerase II | • cell differentiation |
| • hemopoiesis | • myeloid cell differentiation |
| • B cell differentiation |
Pathways
• Hematopoietic cell lineage
• Transcriptional regulation of granulopoiesis
• B cell receptor signaling
• Toll-like receptor signaling (via PU.1 target genes)
Protein Summary
PU.1 is a 272-amino acid protein with an N-terminal transactivation domain and a C-terminal ETS DNA-binding domain. It binds to purine-rich sequences (PU-box) to activate or repress target genes. PU.1 interacts with other transcription factors (e.g., GATA1, C/EBPα) to specify hematopoietic cell fates. Its expression is tightly regulated during hematopoiesis, and its dosage is critical for normal blood cell development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPI1 Knockout HEK293 Cell Line | EDJ-KQ3280 | Human | 6688 | Details Get a Quote |
| SPI1 Knockout HeLa Cell Line | EDJ-KQ54544 | Human | 6688 | Details Get a Quote |
| SPI1 Knockout A-549 Cell Line | EDJ-KQ63028 | Human | 6688 | Details Get a Quote |
| SPI1 Knockout HCT 116 Cell Line | EDJ-KQ71504 | Human | 6688 | Details Get a Quote |
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