STAT5B

gene
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Summary

STAT5B (signal transducer and activator of transcription 5B, HGNC:11367) is a protein-coding gene on chromosome 17q21.2, encoding Signal transducer and activator of transcription 5B (P51692). Carries out a dual function: signal transduction and activation of transcription.

The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein mediates the signal transduction triggered by various cell ligands, such as IL2, IL4, CSF1, and different growth hormones. It has been shown to be involved in diverse biological processes, such as TCR signaling, apoptosis, adult mammary gland development, and sexual dimorphism of liver gene expression. This gene was found to fuse to retinoic acid receptor-alpha (RARA) gene in a small subset of acute promyelocytic leukemias (APLL). The dysregulation of the signaling pathways mediated by this protein may be the cause of the APLL.

Source: NCBI Gene 6777 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): growth hormone insensitivity with immune dysregulation 1, autosomal recessive (Definitive, ClinGen) — +3 more curated relationships
  • GWAS associations: 18
  • Clinical variants (ClinVar): 601 total — 26 pathogenic, 6 likely-pathogenic
  • Phenotypes (HPO): 57
  • Druggable target: yes — 1 molecules with ChEMBL bioactivity
  • Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
  • Transcription factor: yes — 112 downstream targets (CollecTRI)
  • MANE Select transcript: NM_012448

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11367
Approved symbolSTAT5B
Namesignal transducer and activator of transcription 5B
Location17q21.2
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000173757
Ensembl biotypeprotein_coding
OMIM604260
Entrez6777

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 23 protein_coding, 13 retained_intron, 9 nonsense_mediated_decay

ENST00000293328, ENST00000415845, ENST00000468312, ENST00000468496, ENST00000481253, ENST00000481517, ENST00000498674, ENST00000698774, ENST00000698775, ENST00000698776, ENST00000698777, ENST00000698778, ENST00000698779, ENST00000698801, ENST00000698802, ENST00000698803, ENST00000698804, ENST00000698805, ENST00000698806, ENST00000698807, ENST00000698808, ENST00000698809, ENST00000698810, ENST00000698811, ENST00000698812, ENST00000698813, ENST00000698814, ENST00000698815, ENST00000698816, ENST00000698817, ENST00000903577, ENST00000903578, ENST00000903579, ENST00000914413, ENST00000914414, ENST00000914415, ENST00000914416, ENST00000914417, ENST00000951701, ENST00000951702, ENST00000951703, ENST00000951704, ENST00000951705, ENST00000951706, ENST00000951707

RefSeq mRNA: 1 — MANE Select: NM_012448 NM_012448

CCDS: CCDS11423

Canonical transcript exons

ENST00000293328 — 19 exons

ExonStartEnd
ENSE000012935554219917742201864
ENSE000016263324222338242223556
ENSE000036597674222752942227685
ENSE000039747114221040342210497
ENSE000039747124221737742217464
ENSE000039747134221872342218878
ENSE000039747144221198442212190
ENSE000039747154221716042217282
ENSE000039747174221815142218330
ENSE000039747184221601442216106
ENSE000039747304220755842207728
ENSE000039747314220234042202447
ENSE000039747324222477942224868
ENSE000039747344220275742202808
ENSE000039747384221017142210301
ENSE000039747404221971242219842
ENSE000039748264221931242219463
ENSE000039748354227624842276391
ENSE000039748414223200042232137

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7245 / max 399.4841, expressed in 1786 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
16612413.11791784
1661250.356999
1661230.249791

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
bloodUBERON:000017897.52gold quality
body of uterusUBERON:000985396.77gold quality
left uterine tubeUBERON:000130396.64gold quality
right ovaryUBERON:000211896.40gold quality
left ovaryUBERON:000211996.31gold quality
type B pancreatic cellCL:000016996.11gold quality
paraflocculusUBERON:000535196.11gold quality
frontal poleUBERON:000279595.87gold quality
granulocyteCL:000009495.36gold quality
middle frontal gyrusUBERON:000270295.30gold quality
endocervixUBERON:000045895.26gold quality
left adrenal gland cortexUBERON:003582595.25gold quality
left adrenal glandUBERON:000123495.08gold quality
mucosa of stomachUBERON:000119995.05gold quality
right adrenal glandUBERON:000123395.00gold quality
cerebellar hemisphereUBERON:000224594.85gold quality
cerebellar cortexUBERON:000212994.80gold quality
hindlimb stylopod muscleUBERON:000425294.79gold quality
gastrocnemiusUBERON:000138894.77gold quality
lymph nodeUBERON:000002994.71gold quality
muscle layer of sigmoid colonUBERON:003580594.69gold quality
myometriumUBERON:000129694.65gold quality
muscle of legUBERON:000138394.63gold quality
right adrenal gland cortexUBERON:003582794.63gold quality
adrenal cortexUBERON:000123594.57gold quality
cerebellumUBERON:000203794.54gold quality
adrenal glandUBERON:000236994.49gold quality
right hemisphere of cerebellumUBERON:001489094.48gold quality
bone marrow cellCL:000209294.26gold quality
right coronary arteryUBERON:000162594.24gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes5.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

112 targets.

TargetRegulation
A2M
AGTUnknown
AKR1C1Unknown
ANP32AActivation
APOC3Activation
AURKA
BCL2Activation
BCL2L1Activation
BCL6Repression
CCND1Unknown
CCND2Activation
CCND3Unknown
CD4Unknown
CD84Activation
CDK6
CDKN1AUnknown
CDKN1B
CDKN2B
CELUnknown
CHORDC1Activation
CISHActivation
CITED2
CREBBP
CSF2Activation
CSN1S1Activation
CSN2Activation
CXCL8Unknown
CXCL9Activation
CYP21A1P
CYP8B1Activation

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPG, NFKB, PPARA, STAT5A, STAT5B, ZNF382

miRNA regulators (miRDB)

101 targeting STAT5B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-8485100.0077.574731
HSA-MIR-5692A100.0074.406850
HSA-MIR-3163100.0077.238605
HSA-MIR-4481100.0066.421669
HSA-MIR-6867-5P100.0082.213464
HSA-MIR-6870-5P99.9968.552115
HSA-MIR-3667-3P99.9967.171636
HSA-MIR-318599.9968.121959
HSA-MIR-453499.9966.581907
HSA-MIR-1213699.9872.815713
HSA-MIR-480399.9871.993117
HSA-MIR-548N99.9871.944170
HSA-MIR-56899.9869.862084
HSA-MIR-4745-5P99.9865.951028
HSA-MIR-50799.9770.111915
HSA-MIR-4723-5P99.9768.702034
HSA-MIR-569899.9768.492029
HSA-MIR-7111-5P99.9768.482062
HSA-MIR-55799.9670.011640
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-9983-3P99.9471.483631
HSA-MIR-141-3P99.9472.792421
HSA-MIR-200A-3P99.9472.682420
HSA-MIR-6845-3P99.9466.881439
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-95-5P99.8972.173973
HSA-MIR-129-5P99.8870.263273

Literature-anchored findings (GeneRIF, showing 40)

  • The data presented here demonstrate that, in contrast to activation by the cytokine, growth hormone (GH), the activation of STAT5b by the growth factor, epidermal growth factor (EGF), requires overexpression of the EGF receptor (EGFR). (PMID:11751923)
  • STAT5 isoform expression, GM-CSF-induced STAT5 activation, and STAT5 target-gene expression are altered significantly during monocyte/macrophage differentiation (PMID:11867689)
  • increase in Cyclin D1 promoter activity is predominantly mediated by the Jak2/Stat5 signaling pathway. PRL induces Stat5a and 5b to bind to Cyclin D1 promoter (PMID:11923474)
  • Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with STAT3 and STAT5 signaling pathways. (PMID:11929748)
  • Oligomerization of the coiled-coil domain of Stat5 in the Stat5-RARalpha fusion protein leads to stable binding of the corepressor SMRT and is accompanied by an impaired response to differentiation signals in hematopoietic cell (PMID:11929749)
  • Up-regulation of RFC2 and the kinase pim-1 by BCR/ABL requires activation of STAT5b by signaling from SH3+SH2 domains of BCR/ABL. (PMID:12036885)
  • Our study thus suggests a functional cooperation between AR and Stat5. (PMID:12089361)
  • No evidence was found for STAT5b rearrangement at the chromosomal or molecular levels in primary leukemias. STAT5 activation is probably a secondary event in most leukemias. (PMID:12145702)
  • CPAP was found to augment Stat5-mediated transcription. (PMID:12198240)
  • Signal transducer and activator of transcription (Stat)5a and Stat5b are critical for normal immune function. (PMID:12377952)
  • role in mediating synergism between c-src and epidermal growth factor receptor (PMID:12429742)
  • role in suppressing transcriptional activity of estrogen receptors and inducing apoptosis in breast cancer cells (PMID:12642867)
  • Role of c-Jun-N-terminal kinase and signal transducer and activator of transcription 5 in regulation of eosinophil apoptosis by nitric oxide. (PMID:12847485)
  • Stat5 plays an important role in IFN-signaling and participates in the induction of Type I IFN-dependent responses. (PMID:12901872)
  • In tissues from 33 individuals with head and neck cancer, Stat5 activation levels were correlated with progression to a malignant phenotype. (PMID:14583472)
  • Mpl-L-treated Stat5b-deficient mice demonstrated significantly delayed hematopoietic recovery, while Stat5b-deficient mice did not (PMID:14662325)
  • diminished N-domain-mediated oligomerization affected transcriptional activation by both Stat1 and Stat5a/b in a promoter-specific manner. (PMID:15010467)
  • Crossing the STAT5b constitutively active transgene onto the IL-7 receptor-deficient background restores immature B and mature B cell populations as seen by significant increases of immature B and mature B cells. (PMID:15067053)
  • Stat5B is activated by pathways involving FGFR3 and Pyk2 (PMID:15105428)
  • Perturbation of STAT5a&b expression by addition of ODNs decreased proliferative potential of the CML and the AML blasts as well as enhanced their apoptosis (PMID:15128421)
  • requisite role of the Jak2/Stat5B pathway in mediating episodic growth hormone regulation of CYP2C11 (PMID:15591245)
  • Stat5 activation results in the induction of pax5 and bcl-xL in early thymic lymphoid progenitor cells and thereby redirects these cells down the B cell lineage. (PMID:15944278)
  • Study shows that active Stat5 distinguished prostate cancer patients whose disease is likely to progress earlier; therefore, active Stat5 may be a useful marker for selection of more individualized treatment. (PMID:16115927)
  • STAT5b may mediate the transcriptional activation of cyclin D1 after hypoxic stimulation. (PMID:16155412)
  • IFNalpha induces the activation of STAT5 in melanoma cells, and in STAT5-overexpressing cells, this contributes to IFNalpha resistance. (PMID:16169484)
  • Stat5b A630P mutant is an inactive transcription factor by virtue of its aberrant folding and diminished solubility triggered by a misfolded SH2 domain. (PMID:16303763)
  • STAT5b is an inefficient signal transducer and transcription factor, the detrimental impact on signaling pathways important for normal growth and immunity explains, in part, the complex clinical phenotype of GH insensitivity and immune dysfunction (PMID:16464942)
  • STAT5A and STAT5B may play significant roles in the growth and the process of apoptosis of selected human cutaneous T-cell lymphoma cells. (PMID:16502315)
  • STAT5b and HNF4alpha exhibit bi-directional cross-talk that may augment HNF4alpha-dependent gene transcription while inhibiting STAT5b transcriptional activity via the inhibitory effects of HNF4alpha on JAK2 phosphorylation (PMID:16584384)
  • STAT5 is a direct binding partner to EGFR and ErbB4. (PMID:16729043)
  • Cytoskeleton plays an important role in STAT5 activation and translocation into the nucleus in MCF7 cells stimulated with EGF. (PMID:16765629)
  • STAT5b activity in breast cancer cells is modulated by various mutations of tyrosines within the transactivation domain. (PMID:16772534)
  • Data show that STAT5 binds in vivo to the NCAM2 intron in the NKL natural killer cell line and that this binding is induced by cytokines that activate STAT5. (PMID:16840779)
  • Transgenic constitutively activated STAT5b-CA naive CD4+ T cells display a 4-fold greater expression of IL-15 receptor alpha chain on their surface when compared with wild-type T cells. (PMID:16887981)
  • STAT5b propagates an important IL-2-mediated signal for the in vivo accumulation of functional regulatory T cells (PMID:16920911)
  • Therapeutic activation of the GH:STAT5b axis therefore represents a novel target for restoring both normal anabolic metabolism and mucosal tolerance in CD. (PMID:17148664)
  • STAT5 expression was elevated in nasal NK/T cell lymphoma. (PMID:17225522)
  • Defective STAT5b is an etiology for IGF deficiency and the growth hormone insensitivity phenotype. (PMID:17389811)
  • ability of prolactin to activate Stat5 and activating protein-1 was inversely related in mammary cell lines (PMID:17438530)
  • in addition to growth arrest and induced differentiation, OSM also sensitizes normal and transformed osteoblasts to apoptosis by a mechanism implicating (i) activation and nuclear translocation of STAT5 and p53 and (ii) an increased Bax/Bcl-2 ratio (PMID:17471233)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriostat5aENSDARG00000019392
danio_reriostat5bENSDARG00000055588
mus_musculusStat5bENSMUSG00000020919
rattus_norvegicusStat5bENSRNOG00000019075
drosophila_melanogasterStat92EFBGN0016917

Paralogs (6): STAT1 (ENSG00000115415), STAT5A (ENSG00000126561), STAT4 (ENSG00000138378), STAT6 (ENSG00000166888), STAT3 (ENSG00000168610), STAT2 (ENSG00000170581)

Protein

Protein identifiers

Signal transducer and activator of transcription 5BP51692 (reviewed: P51692)

All UniProt accessions (11): P51692, A0A8V8TM84, A0A8V8TM91, A0A8V8TMA6, A0A8V8TMP4, A0A8V8TMQ6, A0A8V8TMR0, A0A8V8TP00, A0A8V8TP16, A0A8V8TP21, C9J4I3

UniProt curated annotations — full annotation on UniProt →

Function. Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation.

Subunit / interactions. Upon activation, forms homodimers. Forms also heterodimers with related family members. Binds NR3C1. Interacts with NCOA1. Interacts with NMI. Interacts with SOCS7. Interacts (via SH2 domain) with INSR. Interacts with CPEB3; this inhibits STAT5B-mediated transcriptional activation.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Tyrosine phosphorylated in response to signaling via activated KIT, resulting in translocation to the nucleus. Tyrosine phosphorylated in response to signaling via activated FLT3; wild-type FLT3 results in much weaker phosphorylation than constitutively activated mutant FLT3. Alternatively, can be phosphorylated by JAK2. Phosphorylation at Tyr-699 by PTK6 or HCK leads to an increase of its transcriptional activity.

Disease relevance. Growth hormone insensitivity syndrome with immune dysregulation 1, autosomal recessive (GHISID1) [MIM:245590] An autosomal recessive form of growth hormone insensitivity syndrome, a congenital disease characterized by short stature, growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, resistance to exogeneous growth hormone therapy, and recurrent infections. Most, but not all, patients have features of immune dysregulation. The disease is caused by variants affecting the gene represented in this entry. Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant (GHISID2) [MIM:618985] An autosomal dominant form of growth hormone insensitivity syndrome, a congenital disease characterized by short stature, growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, resistance to exogeneous growth hormone therapy, and recurrent infections. GHISID2 patients usually have delayed bone age, delayed puberty, and decreased serum IGF1. Some patients may have features of mild immune dysregulation, such as eczema, increased serum IgE, asthma, or celiac disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the transcription factor STAT family.

RefSeq proteins (1): NP_036580* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000980SH2Domain
IPR001217STATFamily
IPR008967p53-like_TF_DNA-bd_sfHomologous_superfamily
IPR012345STAT_TF_DNA-bd_NHomologous_superfamily
IPR013799STAT_TF_prot_interactionDomain
IPR013800STAT_TF_alphaDomain
IPR013801STAT_TF_DNA-bdDomain
IPR015988STAT_TF_CCHomologous_superfamily
IPR035858STAT5a/5b_DBDDomain
IPR035886STAT5b_SH2Domain
IPR036535STAT_N_sfHomologous_superfamily
IPR036860SH2_dom_sfHomologous_superfamily
IPR046994STAT5_CCDomain
IPR048988STAT_linkerDomain

Pfam: PF00017, PF01017, PF02864, PF02865, PF21354

UniProt features (58 total): helix 18, strand 17, sequence variant 6, turn 6, modified residue 5, mutagenesis site 2, chain 1, domain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDBMethodResolution (Å)
6MBZX-RAY DIFFRACTION3.21
6MBWX-RAY DIFFRACTION3.29

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P51692-F185.900.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 90, 128, 193, 682, 699

Mutagenesis-validated functional residues (2):

PositionPhenotype
684abolishes interaction with insr.
699abolishes phosphorylation by hck.

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

IDPathway
R-HSA-1170546Prolactin receptor signaling
R-HSA-1266695Interleukin-7 signaling
R-HSA-1433557Signaling by SCF-KIT
R-HSA-1839117Signaling by cytosolic FGFR1 fusion mutants
R-HSA-186763Downstream signal transduction
R-HSA-2586552Signaling by Leptin
R-HSA-512988Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-8854691Interleukin-20 family signaling
R-HSA-8983432Interleukin-15 signaling
R-HSA-8985947Interleukin-9 signaling
R-HSA-9020558Interleukin-2 signaling
R-HSA-9020958Interleukin-21 signaling
R-HSA-9027283Erythropoietin activates STAT5
R-HSA-9645135STAT5 Activation
R-HSA-9670439Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants
R-HSA-9674555Signaling by CSF3 (G-CSF)
R-HSA-9702518STAT5 activation downstream of FLT3 ITD mutants
R-HSA-9703465Signaling by FLT3 fusion proteins
R-HSA-9705462Inactivation of CSF3 (G-CSF) signaling
R-HSA-982772Growth hormone receptor signaling
R-HSA-9976102Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1226099Signaling by FGFR in disease
R-HSA-1280215Cytokine Signaling in Immune system
R-HSA-162582Signal Transduction
R-HSA-1643685Disease
R-HSA-168256Immune System
R-HSA-1839124FGFR1 mutant receptor activation
R-HSA-186797Signaling by PDGF
R-HSA-449147Signaling by Interleukins
R-HSA-451927Interleukin-2 family signaling

MSigDB gene sets: 681 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, WWTAAGGC_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_RESPONSE_TO_ESTRADIOL, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (63): mitotic cell cycle (GO:0000278), luteinization (GO:0001553), natural killer cell differentiation (GO:0001779), natural killer cell proliferation (GO:0001787), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), defense response (GO:0006952), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), female pregnancy (GO:0007565), lactation (GO:0007595), regulation of steroid metabolic process (GO:0019218), cytokine-mediated signaling pathway (GO:0019221), taurine metabolic process (GO:0019530), lipid storage (GO:0019915), B cell differentiation (GO:0030183), erythrocyte differentiation (GO:0030218), regulation of epithelial cell differentiation (GO:0030856), response to estradiol (GO:0032355), positive regulation of interleukin-2 production (GO:0032743), positive regulation of natural killer cell proliferation (GO:0032819), positive regulation of natural killer cell differentiation (GO:0032825), cellular response to hormone stimulus (GO:0032870), myeloid cell apoptotic process (GO:0033028), negative regulation of myeloid cell apoptotic process (GO:0033033), T cell differentiation in thymus (GO:0033077), erythropoietin-mediated signaling pathway (GO:0038162), regulation of multicellular organism growth (GO:0040014), positive regulation of multicellular organism growth (GO:0040018), positive regulation of activated T cell proliferation (GO:0042104), regulation of cell population proliferation (GO:0042127), natural killer cell mediated cytotoxicity (GO:0042267), progesterone metabolic process (GO:0042448), gamma-delta T cell differentiation (GO:0042492), T cell homeostasis (GO:0043029), response to peptide hormone (GO:0043434), positive regulation of B cell differentiation (GO:0045579), positive regulation of gamma-delta T cell differentiation (GO:0045588), negative regulation of erythrocyte differentiation (GO:0045647), positive regulation of erythrocyte differentiation (GO:0045648), positive regulation of mitotic cell cycle (GO:0045931)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), nuclear glucocorticoid receptor binding (GO:0035259), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein dimerization activity (GO:0046983), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-13 pathways:

CategoryPathways
Interleukin-2 family signaling4
Cytokine Signaling in Immune system3
Signaling by Interleukins3
Signaling by Receptor Tyrosine Kinases1
FGFR1 mutant receptor activation1
Signaling by PDGF1
Signal Transduction1
Signaling by Erythropoietin1
FLT3 Signaling1
Signaling by KIT in disease1
Signaling by FLT3 ITD and TKD mutants1
FLT3 signaling in disease1
Signaling by CSF3 (G-CSF)1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
lymphocyte differentiation2
natural killer cell activation2
regulation of DNA-templated transcription2
binding2
protein binding2
cell cycle1
mitotic nuclear division1
female gonad development1
ovulation cycle process1
lymphocyte proliferation1
transcription by RNA polymerase II1
DNA-templated transcription1
response to stress1
cell surface receptor signaling pathway via STAT1
multi-organism reproductive process1
multi-multicellular organism process1
body fluid secretion1
mammary gland development1
milk ejection reflex1
steroid metabolic process1
regulation of lipid metabolic process1
cell surface receptor signaling pathway1
cellular response to cytokine stimulus1
alkanesulfonate metabolic process1
nutrient storage1
B cell activation1
myeloid cell differentiation1
erythrocyte homeostasis1
epithelial cell differentiation1
regulation of cell differentiation1
regulation of multicellular organismal development1
response to lipid1
response to oxygen-containing compound1
positive regulation of cytokine production1
interleukin-2 production1
regulation of interleukin-2 production1
natural killer cell proliferation1
positive regulation of natural killer cell activation1

Protein interactions and networks

STRING

3734 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
STAT5BJAK2O60674997
STAT5BJAK1P23458986
STAT5BCRKLP46109983
STAT5BSTAT3P40763968
STAT5BJAK3P52333956
STAT5BEPORP19235947
STAT5BTYK2P29597934
STAT5BIL7P13232925
STAT5BIL2P01585916
STAT5BEGFRP00533907
STAT5BEZH2Q15910901
STAT5BGHRP10912897
STAT5BIL7RP16871885
STAT5BSTAT1P42224879
STAT5BCSF2P04141877

IntAct

126 interactions, top by confidence:

ABTypeScore
STAT5BMRPS6psi-mi:“MI:0915”(physical association)0.670
STAT5APDHA1psi-mi:“MI:0914”(association)0.640
STAT5BNMIpsi-mi:“MI:0915”(physical association)0.630
NMISTAT5Bpsi-mi:“MI:0915”(physical association)0.630
STAT5BSTAT5Bpsi-mi:“MI:0407”(direct interaction)0.620
ZNF410STAT5Bpsi-mi:“MI:0915”(physical association)0.560
STACSTAT5Bpsi-mi:“MI:0915”(physical association)0.560
STAT5BZNF410psi-mi:“MI:0915”(physical association)0.560
STAT5BLGALS14psi-mi:“MI:0915”(physical association)0.560
SUOXSTAT5Bpsi-mi:“MI:0915”(physical association)0.560
USP2STAT5Bpsi-mi:“MI:0915”(physical association)0.560
STAT5BCHAF1Apsi-mi:“MI:0915”(physical association)0.560
STAT5BMED25psi-mi:“MI:0915”(physical association)0.560
STAT5BSTACpsi-mi:“MI:0915”(physical association)0.560
STAT5BPIK3R3psi-mi:“MI:0915”(physical association)0.560
STAT5BTSSK3psi-mi:“MI:0915”(physical association)0.560
CDKN1ASTAT5Bpsi-mi:“MI:0915”(physical association)0.560
STAT5BLMO4psi-mi:“MI:0915”(physical association)0.560
STAT5BRBBP4psi-mi:“MI:0915”(physical association)0.560

BioGRID (126): MCMBP (Co-fractionation), STAT5B (Co-fractionation), STAT5B (Affinity Capture-MS), DLAT (Affinity Capture-MS), DLD (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), PDHA1 (Affinity Capture-MS), PDHB (Affinity Capture-MS), PDHX (Affinity Capture-MS), MVP (Affinity Capture-MS), KANSL3 (Affinity Capture-MS), ASF1B (Affinity Capture-MS), PUS7L (Affinity Capture-MS), GHR (Co-localization), CTLA4 (Co-localization)

ESM2 similar proteins: A0M8U1, A6H6W9, A6QL63, F1LSG8, O14639, P42229, P42230, P42232, P51692, P52632, P97875, Q12800, Q13330, Q1RLU8, Q2PG42, Q4V860, Q5RAN1, Q5RBB8, Q5ZKV9, Q62599, Q6AYJ2, Q6GQW0, Q6NRB5, Q6NZH6, Q6ZUT9, Q78E65, Q7T2U9, Q7Z6J6, Q8BR65, Q8CI71, Q8K4B0, Q8K4G5, Q8K4Q0, Q8N122, Q8R3S6, Q8WYK2, Q95115, Q9D2N4, Q9ERA0, Q9H7L9

Diamond homologs: O02799, P40763, P42224, P42225, P42227, P42228, P42229, P42230, P42231, P42232, P51692, P52630, P52631, P52632, P61635, Q14765, Q19S50, Q62771, Q6DV79, Q764M5, Q7ZXK3, Q95115, Q9PVX8, Q9TUM3, Q9TUZ0, Q9TUZ1, Q9WVL2, B5X561, Q24151, Q54BD4, O00910, P42226, P52633, Q61AP6, Q7QDU4, Q70GP4, Q9NAD6

SIGNOR signaling

13 interactions.

AEffectBMechanism
NCOA1up-regulatesSTAT5Bbinding
EGFRup-regulatesSTAT5Bphosphorylation
PTK6up-regulatesSTAT5Bphosphorylation
EGFR“up-regulates activity”STAT5Bphosphorylation
PTPN2“down-regulates activity”STAT5Bdephosphorylation
EPHA4“up-regulates activity”STAT5Bphosphorylation
LCK“up-regulates activity”STAT5Bphosphorylation
JAK2up-regulatesSTAT5Bphosphorylation
PTPN1down-regulatesSTAT5Bdephosphorylation
SRCup-regulatesSTAT5Bphosphorylation
PTPN1“down-regulates activity”STAT5Bdephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Growth hormone receptor signaling556.6×4e-06
Downstream signal transduction545.3×1e-05
Signaling by ALK in cancer638.8×3e-06
Signaling by ALK fusions and activated point mutants725.0×3e-06
Signaling by Interleukins710.7×2e-04
Diseases of signal transduction by growth factor receptors and second messengers79.5×3e-04
PIP3 activates AKT signaling58.0×6e-03
Cytokine Signaling in Immune system76.8×2e-03

GO biological processes:

GO termPartnersFoldFDR
cell surface receptor signaling pathway via JAK-STAT631.7×1e-05
negative regulation of cell population proliferation96.9×7e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — OVT.

Clinical variants and AI predictions

ClinVar

601 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic26
Likely pathogenic6
Uncertain significance282
Likely benign241
Benign18

Top pathogenic / likely-pathogenic (30)

Variant IDHGVSClassification
1074067NM_012448.4(STAT5B):c.121C>T (p.Gln41Ter)Pathogenic
1394582NM_012448.4(STAT5B):c.2065G>T (p.Glu689Ter)Pathogenic
1408216NM_012448.4(STAT5B):c.424_427del (p.Leu142fs)Pathogenic
1453821NM_012448.4(STAT5B):c.1009C>T (p.Gln337Ter)Pathogenic
1686232NM_012448.4(STAT5B):c.1718G>A (p.Trp573Ter)Pathogenic
2003395NM_012448.4(STAT5B):c.415C>T (p.Gln139Ter)Pathogenic
2018391NM_012448.4(STAT5B):c.16C>T (p.Gln6Ter)Pathogenic
2119313NM_012448.4(STAT5B):c.1749del (p.Lys583fs)Pathogenic
2425815NC_000017.10:g.(?40371710)(40371880_?)delPathogenic
2570987NM_012448.4(STAT5B):c.2135_2139dup (p.Ala714Ter)Pathogenic
2739237NM_012448.4(STAT5B):c.89_90dup (p.Arg31fs)Pathogenic
2840836NM_012448.4(STAT5B):c.1213_1229del (p.Tyr405fs)Pathogenic
2852676NM_012448.4(STAT5B):c.303C>A (p.Cys101Ter)Pathogenic
2869095NM_012448.4(STAT5B):c.1906C>T (p.Gln636Ter)Pathogenic
3384021NM_012448.4(STAT5B):c.1892G>A (p.Trp631Ter)Pathogenic
3641526NM_012448.4(STAT5B):c.245del (p.Leu82fs)Pathogenic
4718768NM_012448.4(STAT5B):c.240_241del (p.Leu82fs)Pathogenic
4804939NM_012448.4(STAT5B):c.1183G>T (p.Glu395Ter)Pathogenic
492931NM_012448.4(STAT5B):c.1421A>G (p.Gln474Arg)Pathogenic
522611NM_012448.4(STAT5B):c.530A>C (p.Gln177Pro)Pathogenic
5694NM_012448.4(STAT5B):c.1888G>C (p.Ala630Pro)Pathogenic
5695NM_012448.4(STAT5B):c.1191dup (p.Asn398fs)Pathogenic
5697NM_012448.4(STAT5B):c.454C>T (p.Arg152Ter)Pathogenic
5698NM_012448.4(STAT5B):c.1680+1delPathogenic
579749NM_012448.4(STAT5B):c.1102dup (p.Gln368fs)Pathogenic
840661NM_012448.4(STAT5B):c.1102del (p.Gln368fs)Pathogenic
1066569NM_012448.4(STAT5B):c.1906+1G>ALikely pathogenic
2446384NM_012448.4(STAT5B):c.1896G>T (p.Lys632Asn)Likely pathogenic
2955379NM_012448.4(STAT5B):c.1681-2A>GLikely pathogenic
3067804NM_012448.4(STAT5B):c.1474-2_1474delinsTLikely pathogenic

SpliceAI

3936 predictions. Top by Δscore:

VariantEffectΔscore
17:42201860:CAGGG:Cacceptor_gain1.0000
17:42201861:AGGG:Aacceptor_gain1.0000
17:42201862:GGG:Gacceptor_gain1.0000
17:42201863:GG:Gacceptor_gain1.0000
17:42201865:C:CCacceptor_gain1.0000
17:42201865:C:CGacceptor_loss1.0000
17:42201866:T:Cacceptor_gain1.0000
17:42201866:T:TCacceptor_gain1.0000
17:42202338:A:ACdonor_gain1.0000
17:42202339:C:CCdonor_gain1.0000
17:42202339:CTT:Cdonor_gain1.0000
17:42202341:T:TAdonor_gain1.0000
17:42202377:CAG:Cdonor_gain1.0000
17:42202379:G:Cdonor_gain1.0000
17:42202443:CAAAC:Cacceptor_gain1.0000
17:42202444:AAAC:Aacceptor_gain1.0000
17:42202445:AAC:Aacceptor_gain1.0000
17:42202446:AC:Aacceptor_gain1.0000
17:42202447:CC:Cacceptor_gain1.0000
17:42202448:C:CAacceptor_loss1.0000
17:42202448:C:CCacceptor_gain1.0000
17:42202449:T:Aacceptor_loss1.0000
17:42202755:A:ACdonor_gain1.0000
17:42202756:C:CCdonor_gain1.0000
17:42202756:CT:Cdonor_gain1.0000
17:42202809:C:CCacceptor_gain1.0000
17:42207605:T:TAdonor_gain1.0000
17:42207727:CT:Cacceptor_gain1.0000
17:42207729:C:CCacceptor_gain1.0000
17:42207736:A:Tacceptor_gain1.0000

AlphaMissense

5207 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:42202775:A:GI704T1.000
17:42202791:A:GY699H1.000
17:42207610:T:AK675N1.000
17:42207610:T:GK675N1.000
17:42207638:A:GL666P1.000
17:42207659:C:GR659P1.000
17:42207674:C:GR654P1.000
17:42207701:G:CP645R1.000
17:42207701:G:TP645H1.000
17:42207702:G:AP645S1.000
17:42207702:G:TP645T1.000
17:42207707:A:GL643P1.000
17:42210186:A:GW631R1.000
17:42210186:A:TW631R1.000
17:42210188:G:TA630D1.000
17:42210189:C:GA630P1.000
17:42210191:A:TI629N1.000
17:42210194:G:AT628I1.000
17:42210200:C:TG626D1.000
17:42210201:C:GG626R1.000
17:42210203:C:AG625V1.000
17:42210203:C:TG625D1.000
17:42210204:C:GG625R1.000
17:42210213:A:GS622P1.000
17:42210215:T:AD621V1.000
17:42210216:C:AD621Y1.000
17:42210216:C:GD621H1.000
17:42210217:A:CS620R1.000
17:42210217:A:TS620R1.000
17:42210218:C:AS620I1.000

dbSNP variants (sampled 300 via entrez): RS1000031391 (17:42275922 C>A,T), RS1000065696 (17:42276380 G>A,C), RS1000091526 (17:42199715 G>A), RS1000134836 (17:42268633 T>G), RS1000144168 (17:42282724 C>A), RS1000169291 (17:42237952 C>T), RS1000177069 (17:42283011 A>C), RS1000233049 (17:42214828 C>A,T), RS1000267014 (17:42231155 C>T), RS1000269340 (17:42257731 A>G), RS1000330321 (17:42244777 C>T), RS1000356067 (17:42244527 A>G), RS1000400701 (17:42231246 T>A,C), RS1000416868 (17:42276176 G>A), RS1000424638 (17:42289094 T>C)

Disease associations

OMIM: gene MIM:604260 | disease phenotypes: MIM:245590, MIM:618985

GenCC curated gene-disease

DiseaseClassificationInheritance
growth hormone insensitivity syndrome with immune dysregulationDefinitiveSemidominant
growth hormone insensitivity with immune dysregulation 1, autosomal recessiveStrongAutosomal recessive
growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominantStrongAutosomal dominant
growth hormone insensitivity syndromeLimitedAutosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

DiseaseClassificationInheritance
growth hormone insensitivity with immune dysregulation 1, autosomal recessiveDefinitiveAR
growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominantModerateAD

Mondo (4): growth hormone insensitivity with immune dysregulation 1, autosomal recessive (MONDO:0100211), growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant (MONDO:0100219), growth hormone insensitivity syndrome with immune dysregulation (MONDO:0100210), growth hormone insensitivity syndrome (MONDO:0015892)

Orphanet (1): Laron syndrome with immunodeficiency (Orphanet:220465)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000007Autosomal recessive inheritance
HP:0000212Gingival overgrowth
HP:0000225Gingival bleeding
HP:0000252Microcephaly
HP:0000421Epistaxis
HP:0000790Hematuria
HP:0000823Delayed puberty
HP:0000824Decreased response to growth hormone stimulation test
HP:0000964Eczematoid dermatitis
HP:0000967Petechiae
HP:0000978Bruising susceptibility
HP:0000979Purpura
HP:0001324Muscle weakness
HP:0001508Failure to thrive
HP:0001620Abnormally high-pitched voice
HP:0001824Weight loss
HP:0001873Thrombocytopenia
HP:0001875Decreased total neutrophil count
HP:0001876Pancytopenia
HP:0001882Decreased total leukocyte count
HP:0001892Abnormal bleeding
HP:0001903Anemia
HP:0001945Fever
HP:0001974Increased total leukocyte count
HP:0002027Abdominal pain
HP:0002039Anorexia
HP:0002098Respiratory distress
HP:0002321Vertigo
HP:0002608Celiac disease

GWAS associations

18 associations (top):

StudyTraitp-value
GCST001725_55Inflammatory bowel disease6.000000e-22
GCST003602_13Inflammatory bowel disease2.000000e-09
GCST004131_42Inflammatory bowel disease2.000000e-17
GCST004132_58Crohn’s disease2.000000e-11
GCST004133_53Ulcerative colitis1.000000e-10
GCST005038_98Allergic disease (asthma, hay fever or eczema)1.000000e-09
GCST007995_3Asthma (childhood onset)5.000000e-09
GCST009191_13Paracentral lobule volume8.000000e-06
GCST009720_67Asthma2.000000e-08
GCST010042_25Asthma3.000000e-11
GCST90002388_497Lymphocyte count6.000000e-09
GCST90002389_233Lymphocyte percentage of white cells4.000000e-10
GCST90002399_241Neutrophil percentage of white cells5.000000e-11
GCST90014325_64Asthma3.000000e-09
GCST90020024_517A body shape index2.000000e-08
GCST90020025_1437Waist-to-hip ratio adjusted for BMI8.000000e-13
GCST90020027_459Waist-hip index3.000000e-13
GCST90020029_484Waist circumference adjusted for body mass index5.000000e-08

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0004587lymphocyte count
EFO:0007993lymphocyte percentage of leukocytes
EFO:0007990neutrophil percentage of leukocytes
EFO:0007789BMI-adjusted waist circumference
EFO:0007788BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

DescriptorNameTree numbers
C537871Laron syndrome type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL4523625 (PROTEIN FAMILY), CHEMBL4523698 (PROTEIN-PROTEIN INTERACTION), CHEMBL5817 (SINGLE PROTEIN), CHEMBL6196141 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,743 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL413376SURAMIN HEXASODIUM32,743

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
4-(Nonanamidomethyl)-1,2-phenylene bis(dihydrogen phosphate) (6b)IC5024900 nM
4-((8-Methylnonanamido)methyl)-1,2-phenylene bis(dihydrogen phosphate) (6a)IC5026400 nM
2-Methoxy-4-(nonanamidomethyl)phenyl dihydrogen phosphate (3b)IC5098000 nM

ChEMBL bioactivities

68 potent at pChembl≥5 of 73 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.37Kd4.225nMCHEMBL5653589
8.35ED504.463nMCHEMBL5653589
7.70EC5020nMCHEMBL578201
7.40EC5040nMCHEMBL570002
7.40EC5040nMCHEMBL569720
7.38Kd42nMCHEMBL3358611
6.84Ki145.8nMCHEMBL3358611
6.81IC50154nMCHEMBL4088092
6.70Ki200nMCHEMBL6161430
6.66IC50220nMCHEMBL4104462
6.63IC50234nMCHEMBL4103576
6.62IC50240nMCHEMBL4085646
6.58IC50260nMCHEMBL4104019
6.57IC50270nMCHEMBL4080219
6.55IC50280nMCHEMBL4066274
6.54IC50290nMCHEMBL4086096
6.48IC50330nMCHEMBL4077592
6.46IC50350nMCHEMBL4093849
6.41IC50390nMCHEMBL4080740
6.40Ki400nMCHEMBL5395962
6.34IC50460nMCHEMBL4075745
6.28Ki520nMCHEMBL6169609
6.28Ki530nMCHEMBL6132917
6.23Ki590nMCHEMBL6169593
6.22Ki600nMCHEMBL4549938
6.21IC50620nMCHEMBL4062751
6.18IC50660nMCHEMBL4076474
6.17Ki670nMCHEMBL6148327
6.17Ki680nMCHEMBL6146875
6.10Ki800nMCHEMBL5428281
6.10Ki800nMCHEMBL6173206
6.00Ki1000nMCHEMBL5403493
6.00Ki1000nMCHEMBL5402407
6.00Ki1000nMCHEMBL6150217
5.89Ki1300nMCHEMBL5438554
5.85IC501400nMCHEMBL4483038
5.80Ki1600nMCHEMBL5416509
5.80Ki1600nMCHEMBL5398037
5.77Ki1700nMCHEMBL5395896
5.75Ki1800nMCHEMBL6170089
5.70Ki2000nMCHEMBL5396273
5.68Ki2100nMCHEMBL5430356
5.62Ki2400nMCHEMBL6165055
5.60IC502500nMCHEMBL1253351
5.60Ki2500nMCHEMBL5419146
5.55Ki2800nMCHEMBL1829862
5.54IC502900nMCHEMBL4555061
5.51Ki3100nMCHEMBL5395196
5.47Ki3400nMCHEMBL2023989
5.44Ki3600nMCHEMBL6152739

PubChem BioAssay actives

56 with measured affinity, of 157 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149504: Binding affinity to human STAT5A/STAT5B incubated for 45 mins by Kinobead based pull down assaykd0.0042uM
3-[[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]amino]-6-methyl-5-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazine-2-carbonitrile446092: Inhibition of erythropoietin-stimulated STAT5 expressed in human U2OS cellsec500.0200uM
3-[[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino]-5-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazine-2-carbonitrile446092: Inhibition of erythropoietin-stimulated STAT5 expressed in human U2OS cellsec500.0400uM
3-[[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino]-6-methyl-5-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazine-2-carbonitrile446092: Inhibition of erythropoietin-stimulated STAT5 expressed in human U2OS cellsec500.0400uM
4-[[2-[(4-chlorophenyl)methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]acetyl]-[(3,5-ditert-butylphenyl)methyl]amino]-2-hydroxybenzoic acid1171627: Binding affinity to full-length His-tagged STAT5B (unknown origin) by surface plasmon resonance assaykd0.0420uM
[4-[[[2-[6-(phenylcarbamoyl)naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.1540uM
[4-[[[2-[6-[(4-fluorophenyl)carbamoyl]naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2200uM
[4-[[[2-[6-[(3-fluorophenyl)carbamoyl]naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2340uM
[4-[[[2-[6-[(4-bromophenyl)carbamoyl]naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2400uM
[4-[[[2-[6-[(3-chlorophenyl)carbamoyl]naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2600uM
[4-[[[2-[6-[(4-chlorophenyl)carbamoyl]naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2700uM
[4-[[[2-[4-(phenylcarbamoyl)phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2800uM
[4-[[[2-[6-[(3-bromophenyl)carbamoyl]naphthalen-2-yl]oxyacetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.2900uM
[4-[[[2-[4-[(4-chlorophenyl)carbamoyl]phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.3300uM
[4-[(8-methylnonanoylamino)methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1801347: Fluorescence Polarization Assay from Article 10.1021/acschembio.5b00817: “Phosphorylation of Capsaicinoid Derivatives Provides Highly Potent and Selective Inhibitors of the Transcription Factor STAT5b.”ki0.3400uM
[4-[[[2-[4-[(4-fluorophenyl)carbamoyl]phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.3500uM
[4-[(nonanoylamino)methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1801347: Fluorescence Polarization Assay from Article 10.1021/acschembio.5b00817: “Phosphorylation of Capsaicinoid Derivatives Provides Highly Potent and Selective Inhibitors of the Transcription Factor STAT5b.”ki0.3900uM
[4-[[[2-[4-[(4-bromophenyl)carbamoyl]phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.3900uM
[[2-[[(2S)-1-[(2S)-2-[1,3-benzothiazol-5-yl-[3-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pent-4-ynylamino]-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki0.4000uM
[4-[[[2-[4-[(3-chlorophenyl)carbamoyl]phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.4600uM
4-[[5-(4-fluorophenyl)tetrazol-1-yl]methylamino]-1,2,5-oxadiazole-3-carboxylic acid1559612: Binding affinity to MBP-tagged recombinant STAT5b-SH2 domain (unknown origin) using carboxyfluoresceine-labeled phosphotyrosine octapeptide incubated for 12 hrs by fluorescence polarization assayki0.6000uM
[4-[[[2-[4-[(3-fluorophenyl)carbamoyl]phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.6200uM
[4-[[[2-[4-[(3-bromophenyl)carbamoyl]phenoxy]acetyl]amino]methyl]-2-phosphonooxyphenyl] dihydrogen phosphate1485961: Displacement of 5-carboxyfluorescein-GY(PO3H2)LVLDKW from STAT5B SH2 domain (unknown origin) pretreated for 1 hr followed by fluorescent tracer addition after 1 hr by fluorescence polarization assayic500.6600uM
[[2-[[(2S)-1-[(2S)-2-[1-benzothiophen-5-yl-[3-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pent-4-ynylamino]-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki0.8000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-naphthalen-2-ylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki1.0000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki1.0000uM
[[2-[[(2S)-1-[(2S)-2-[1,3-benzothiazol-5-yl-[3-(dimethylamino)-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki1.3000uM
4-(tetrazol-1-ylmethylamino)-1,2,5-oxadiazole-3-carboxylic acid1559612: Binding affinity to MBP-tagged recombinant STAT5b-SH2 domain (unknown origin) using carboxyfluoresceine-labeled phosphotyrosine octapeptide incubated for 12 hrs by fluorescence polarization assayic501.4000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki1.6000uM
[[2-[[(2S)-3-(4-bromophenyl)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki1.6000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-3-(4-fluorophenyl)-1-oxopropan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki1.7000uM
[[2-[[(2S)-1-[(2S)-2-[1-benzofuran-5-yl-[3-(dimethylamino)-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki2.0000uM
[[2-[[(2S)-1-[(2S)-2-[(4-bromophenyl)-[3-(dimethylamino)-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki2.1000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-[4-(trifluoromethyl)phenyl]propan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki2.5000uM
octasodium;4-[[3-[[3,5-bis[(2,4-disulfonatophenyl)carbamoyl]phenyl]carbamoylamino]-5-[(2,4-disulfonatophenyl)carbamoyl]benzoyl]amino]benzene-1,3-disulfonate1486489: Inhibition of 5-carboxyfluorescein-GpYLVLDKW-OH binding to STAT5B SH2 domain (unknown origin) pre-incubated for 1 hr before fluorescent-labelled peptide addition by fluorescence polarization assayic502.5000uM
4-[(4-cyclohexylphenyl)methyl-[2-[methyl-(2,4,6-trimethylphenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid658686: Displacement of 5-carboxyfluorescein-labeled GpYLVLDKW from the STAT5b-SH2 domain after 15 mins by fluorescent polarization assayki2.8000uM
4-[(5-benzyltetrazol-1-yl)methylamino]-1,2,5-oxadiazole-3-carboxylic acid1559612: Binding affinity to MBP-tagged recombinant STAT5b-SH2 domain (unknown origin) using carboxyfluoresceine-labeled phosphotyrosine octapeptide incubated for 12 hrs by fluorescence polarization assayic502.9000uM
[[2-[[(1S)-1-cyclopropyl-2-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki3.1000uM
4-[(4-cyclohexylphenyl)methyl-[2-[(4-methylphenyl)sulfonyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetyl]amino]-2-hydroxybenzoic acid658686: Displacement of 5-carboxyfluorescein-labeled GpYLVLDKW from the STAT5b-SH2 domain after 15 mins by fluorescent polarization assayki3.4000uM
2-hydroxy-4-[[4-[4-(3-methoxycarbonylphenyl)phenyl]phenyl]methyl-[2-[methyl-(4-methylphenyl)sulfonylamino]acetyl]amino]benzoic acid658686: Displacement of 5-carboxyfluorescein-labeled GpYLVLDKW from the STAT5b-SH2 domain after 15 mins by fluorescent polarization assayki3.8000uM
[[2-[[(1S)-2-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki4.0000uM
4-[(4-cyclohexylphenyl)methyl-[2-[methyl-(4-phenylphenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid658686: Displacement of 5-carboxyfluorescein-labeled GpYLVLDKW from the STAT5b-SH2 domain after 15 mins by fluorescent polarization assayki4.1000uM
[[2-[[(2S)-1-[(2S)-2-[(4-chlorophenyl)-[3-(dimethylamino)-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki4.2000uM
4-[(3,5-ditert-butylphenyl)methyl-[2-[methyl-(2,4,6-trimethylphenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid1171625: Inhibition of STAT5B SH2 domain (unknown origin)-5-FAM-GpYLVLDKW interaction compound treated for 15 mins by fluorescent polarization assayki4.7700uM
4-[[4-[4-(4-carbamoylphenyl)phenyl]phenyl]methyl-[2-[methyl-(4-methylphenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid658686: Displacement of 5-carboxyfluorescein-labeled GpYLVLDKW from the STAT5b-SH2 domain after 15 mins by fluorescent polarization assayki4.8000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-(4-phenylphenyl)carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki5.2000uM
[[2-[[(2S)-1-[(2S)-2-[[3-(dimethylamino)-3-oxopropyl]-[3-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki6.1000uM
[[2-[[(2S)-1-[(2S)-2-(3,4-dihydro-2H-quinoline-1-carbonyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki6.2000uM
[[2-[[(2S)-3,3-dimethyl-1-[(2S)-2-[methyl(phenyl)carbamoyl]pyrrolidin-1-yl]-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid2027879: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assayki6.2000uM
2-hydroxy-4-[[2-[methyl-(2,4,6-trimethylphenyl)sulfonylamino]acetyl]-(naphthalen-2-ylmethyl)amino]benzoic acid1171625: Inhibition of STAT5B SH2 domain (unknown origin)-5-FAM-GpYLVLDKW interaction compound treated for 15 mins by fluorescent polarization assayki6.6200uM

CTD chemical–gene interactions

85 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, decreases expression, affects expression9
tofacitinibdecreases reaction, increases phosphorylation, decreases phosphorylation4
trichostatin Aaffects cotreatment, decreases expression3
sodium arsenitedecreases expression, increases abundance, increases expression3
bisphenol Adecreases expression, decreases methylation, increases methylation2
WP1066decreases phosphorylation2
(+)-JQ1 compounddecreases phosphorylation, affects binding, decreases reaction, increases reaction, affects localization (+1 more)2
Arsenic Trioxidedecreases expression, decreases activity, decreases phosphorylation2
Vorinostatdecreases expression, affects cotreatment2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
Progesteroneincreases phosphorylation, increases reaction, increases expression, affects localization2
Tretinoindecreases expression2
2-hydroxy-1-(2-((9-(4-methylcyclohexyl)-9H-pyrido(4’,3’-4,5)pyrrolo(2,3-d)pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanonedecreases phosphorylation1
GSK-J4increases expression1
bisphenol Fdecreases methylation1
2,4,6-tribromophenoldecreases expression1
triphenyl phosphateaffects expression1
alpha-naphthoflavoneaffects binding, decreases activity, decreases reaction, increases activity, increases phosphorylation1
benzo(a)pyrene-3,6-quinoneincreases phosphorylation1
cobaltous chloridedecreases expression1
tetrabromobisphenol Adecreases expression1
nickel sulfateincreases expression1
benzo(a)pyrene-1,6-quinoneincreases phosphorylation1
tamibarotenedecreases expression1
norcantharidindecreases phosphorylation1
mono(2-ethyl-5-oxohexyl)phthalatedecreases methylation, increases abundance, increases expression1
CGP 52608affects binding, increases reaction1
RTKI cpddecreases activity, decreases reaction, increases activity, increases phosphorylation1
entinostatdecreases expression1
AG 1879decreases activity, decreases reaction, increases phosphorylation1

ChEMBL screening assays

55 unique, capped per target: 55 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4362110BindingEffect on STAT5a/b at Y694/Y699 phosphorylation level in human NCI-H1975 incubated for 12 hrs by human phosphokinase proteome profiler array relative to controlStructure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer. — Eur J Med Chem

Cellosaurus cell lines

15 cell lines: 10 cancer cell line, 5 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_A8CIHEK-Blue TPOTransformed cell lineFemale
CVCL_B2HLAbcam HeLa STAT5B KOCancer cell lineFemale
CVCL_B8QBAbcam HCT 116 STAT5B KOCancer cell lineMale
CVCL_B9SSAbcam A-549 STAT5B KOCancer cell lineMale
CVCL_C3ESNK-NJCancer cell lineMale
CVCL_D2HCAbcam MCF-7 STAT5B KOCancer cell lineFemale
CVCL_D8BNUbigene A-549 STAT5B KOCancer cell lineMale
CVCL_D8WHUbigene HCT 116 STAT5B KOCancer cell lineMale
CVCL_D9TAUbigene HEK293 STAT5B KOTransformed cell lineFemale
CVCL_E0Q6Ubigene HeLa STAT5B KOCancer cell lineFemale

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00368173PHASE2/PHASE3COMPLETEDIGF-I/IGFBP-3 Therapy in Children and Adolescents With Growth Hormone Insenitivity Syndrome (GHIS) Such as Laron Syndrome
NCT00571727PHASE2/PHASE3COMPLETEDLong-Term Treatment With rhIGF-1 in GHIS