STAT5B: Signal Transducer and Activator of Transcription 5B
A key transcription factor in cytokine and growth factor signaling, implicated in immune regulation, growth, and cancer.
Gene Information Card
| Symbol | STAT5B |
|---|---|
| Full Name | Signal transducer and activator of transcription 5B |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 6777 ncbi.nlm.nih.gov/gene/6777 |
| Ensembl ID | ENSG00000173757 |
| UniProt ID | P51692 |
| OMIM ID | 604260 |
| HGNC ID | 11367 |
| Aliases | STAT5 |
Description
STAT5B (Signal Transducer and Activator of Transcription 5B) is a member of the STAT family of transcription factors. It is activated by various cytokines and growth factors, including growth hormone (GH), prolactin, interleukins (e.g., IL-2, IL-7, IL-15), and erythropoietin. Upon ligand binding to cell surface receptors, STAT5B is phosphorylated by JAK kinases, dimerizes, and translocates to the nucleus to regulate gene expression involved in cell growth, differentiation, survival, and immune function. STAT5B is highly homologous to STAT5A but has distinct roles in growth regulation and immune responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Growth hormone insensitivity with immunodeficiency | Loss-of-function mutations in STAT5B impair GH signaling, leading to growth failure, and disrupt IL-2/IL-7/IL-15 signaling, causing immune deficiency. | OMIM #245590; ClinVar; NCBI |
| Acute lymphoblastic leukemia (ALL) | Constitutive activation of STAT5B (e.g., via JAK2 fusions or STAT5B mutations) promotes leukemogenesis by driving uncontrolled proliferation and survival of lymphoid progenitors. | COSMIC; ClinVar; NCBI |
| Chronic myeloid leukemia (CML) | BCR-ABL1 fusion protein activates STAT5B, contributing to myeloid transformation and resistance to apoptosis. | COSMIC; NCBI |
| Large granular lymphocytic leukemia | Activating STAT5B mutations (e.g., N642H) are recurrent in T-cell large granular lymphocytic leukemia, driving clonal expansion. | COSMIC; ClinVar; NCBI |
| Breast cancer | STAT5B hyperactivation (e.g., via prolactin signaling) is associated with poor prognosis and endocrine therapy resistance. | COSMIC; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 25.6 | Medium |
| Bone marrow | 18.3 | Medium |
| Lung | 15.2 | Medium |
| Spleen | 22.1 | Medium |
| Thymus | 19.8 | Medium |
| Liver | 8.4 | Low |
| Kidney | 7.1 | Low |
| Heart | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | 32.5 | High expression; BCR-ABL positive |
| MCF7 (Breast cancer) | 28.1 | High expression; prolactin responsive |
| Jurkat (T-cell leukemia) | 24.7 | High expression; IL-2 signaling |
| HEK293 (Embryonic kidney) | 12.3 | Moderate expression |
| HepG2 (Liver cancer) | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| N642H | Missense | Recurrent in T-LGL leukemia | Gain-of-function; constitutive activation of STAT5B |
| A630V | Missense | Rare in ALL | Gain-of-function; enhanced dimerization |
| R152W | Missense | Germline in GH insensitivity | Loss-of-function; impaired DNA binding |
| Q474H | Missense | Somatic in breast cancer | Unknown; likely gain-of-function |
| F157S | Missense | Germline in immunodeficiency | Loss-of-function; defective phosphorylation |
Mutation functional classification
Loss of Function (LOF)
Germline mutations (e.g., R152W, F157S) impair STAT5B activation, DNA binding, or nuclear translocation, leading to growth hormone insensitivity and combined immunodeficiency.
Gain of Function (GOF)
Somatic mutations (e.g., N642H, A630V) cause constitutive activation of STAT5B, promoting oncogenic signaling in leukemias and solid tumors.
Dominant Negative (DN)
Some STAT5B mutations (e.g., truncated forms) can act as dominant-negative inhibitors of wild-type STAT5A/B, disrupting normal cytokine signaling.
View complete mutation data：
Gene Ontology (GO)
| • GO:0000978 - RNA polymerase II cis-regulatory region sequence-specific DNA binding | • GO:0003700 - DNA-binding transcription factor activity |
| • GO:0007259 - JAK-STAT signaling cascade | • GO:0042517 - positive regulation of tyrosine phosphorylation of STAT protein |
| • GO:0008284 - positive regulation of cell population proliferation | • GO:0006915 - apoptotic process |
| • GO:0005634 - nucleus | • GO:0005737 - cytoplasm |
Pathways
• JAK-STAT signaling pathway (KEGG hsa04630)
• Prolactin signaling pathway (KEGG hsa04917)
• Growth hormone signaling pathway (KEGG hsa04630)
• IL-2 signaling pathway (Reactome R-HSA-451927)
• IL-7 signaling pathway (Reactome R-HSA-449147)
• Erythropoietin signaling pathway (Reactome R-HSA-9006336)
Protein Summary
STAT5B is a 787-amino acid transcription factor with a conserved structure: an N-terminal domain, coiled-coil domain, DNA-binding domain, linker domain, SH2 domain, and C-terminal transactivation domain. It is activated by tyrosine phosphorylation (primarily at Y699) by JAK kinases, leading to dimerization and nuclear translocation. STAT5B regulates genes involved in cell cycle (e.g., CCND1), anti-apoptosis (e.g., BCL2L1), and immune function (e.g., FOXP3). Its activity is tightly controlled by phosphatases (e.g., PTPN2) and SOCS proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT5B Knockout HEK293 Cell Line | EDJ-KQ539 | Human | 6777 | Details Get a Quote |
| STAT5B Knockout A-549 Cell Line | EDJ-KQ18906 | Human | 6777 | Details Get a Quote |
| STAT5B Knockout HCT 116 Cell Line | EDJ-KQ18907 | Human | 6777 | Details Get a Quote |
| STAT5B Knockout HeLa Cell Line | EDJ-KQ18908 | Human | 6777 | Details Get a Quote |
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