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 is essential for mediating responses to ... See more...

Aliases for STAT4 Gene

Aliases for STAT4 Gene

  • Signal Transducer And Activator Of Transcription 4 2 3 4 5
  • Signal Transducer And Activator Of Transcription 4 Variant 3 3
  • SLEB11 3
  • STAT4 5

External Ids for STAT4 Gene

Previous GeneCards Identifiers for STAT4 Gene

  • GC02M190088
  • GC02M190596
  • GC02M191858
  • GC02M192096
  • GC02M191719
  • GC02M191602
  • GC02M183754
  • GC02M191894

Summaries for STAT4 Gene

Entrez Gene Summary for STAT4 Gene

  • 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 is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

GeneCards Summary for STAT4 Gene

STAT4 (Signal Transducer And Activator Of Transcription 4) is a Protein Coding gene. Diseases associated with STAT4 include Systemic Lupus Erythematosus 11 and Systemic Lupus Erythematosus. Among its related pathways are Immune response IL-23 signaling pathway and GPCR Pathway. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is STAT1.

UniProtKB/Swiss-Prot Summary for STAT4 Gene

  • Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for STAT4 Gene

Genomics for STAT4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for STAT4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around STAT4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for STAT4

Top Transcription factor binding sites by QIAGEN in the STAT4 gene promoter:
  • AP-1
  • Bach1
  • c-Fos
  • c-Jun
  • GATA-3
  • GR
  • GR-alpha
  • IRF-1
  • POU2F1
  • POU2F1a

Genomic Locations for STAT4 Gene

Genomic Locations for STAT4 Gene
chr2:191,029,576-191,172,684
(GRCh38/hg38)
Size:
143,109 bases
Orientation:
Minus strand
chr2:191,894,302-192,016,322
(GRCh37/hg19)
Size:
122,021 bases
Orientation:
Minus strand

Genomic View for STAT4 Gene

Genes around STAT4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
STAT4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for STAT4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for STAT4 Gene

Proteins for STAT4 Gene

  • Protein details for STAT4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14765-STAT4_HUMAN
    Recommended name:
    Signal transducer and activator of transcription 4
    Protein Accession:
    Q14765
    Secondary Accessions:
    • Q96NZ6

    Protein attributes for STAT4 Gene

    Size:
    748 amino acids
    Molecular mass:
    85941 Da
    Quaternary structure:
    • Forms a homodimer or a heterodimer with a related family member. Interacts with ARL2BP (By similarity). The SH2 domain interacts, in vitro, with IL12RB2 via a short cytoplasmic domain.

neXtProt entry for STAT4 Gene

Post-translational modifications for STAT4 Gene

  • Tyrosine phosphorylated. Serine phosphorylation is also required for maximal transcriptional activity (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Abcam antibodies for STAT4

Protein Products

  • Abcam proteins for STAT4

No data available for DME Specific Peptides for STAT4 Gene

Domains & Families for STAT4 Gene

Gene Families for STAT4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Suggested Antigen Peptide Sequences for STAT4 Gene

GenScript: Design optimal peptide antigens:
  • STAT4 (B7SIX5_HUMAN)
  • Signal transducer and activator of transcription 4, isoform CRA_a (D3DPI9_HUMAN)
  • STAT4 (Q53RU2_HUMAN)
  • Signal transducer and activator of transcription 4 (STAT4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14765

UniProtKB/Swiss-Prot:

STAT4_HUMAN :
  • Belongs to the transcription factor STAT family.
Family:
  • Belongs to the transcription factor STAT family.
genes like me logo Genes that share domains with STAT4: view

Function for STAT4 Gene

Molecular function for STAT4 Gene

UniProtKB/Swiss-Prot Function:
Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling.
GENATLAS Biochemistry:
signal transducer and activator of transcription 4,involved in IL12 signal transduction,expressed in spleen,heart,brain

Phenotypes From GWAS Catalog for STAT4 Gene

Gene Ontology (GO) - Molecular Function for STAT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IBA 21873635
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IEA,TAS 9284918
genes like me logo Genes that share ontologies with STAT4: view
genes like me logo Genes that share phenotypes with STAT4: view

Human Phenotype Ontology for STAT4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for STAT4 Gene

MGI Knock Outs for STAT4:

Animal Model Products

CRISPR Products

miRNA for STAT4 Gene

miRTarBase miRNAs that target STAT4

Transcription Factor Targets for STAT4 Gene

Selected GeneGlobe predicted Target genes for STAT4
Targeted motifs for STAT4 Gene
HOMER Transcription Factor Regulatory Elements motif STAT4
  • Consensus sequence: NTTTCCAGGAAA Submotif: canonical Cell Type: CD4 GEO ID: GSE22104

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STAT4

No data available for Enzyme Numbers (IUBMB) for STAT4 Gene

Localization for STAT4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for STAT4 Gene

Cytoplasm. Nucleus. Note=Translocated into the nucleus in response to phosphorylation.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for STAT4 gene
Compartment Confidence
nucleus 5
cytosol 4
extracellular 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endosome 2
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for STAT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IEA,IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with STAT4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for STAT4 Gene

Pathways & Interactions for STAT4 Gene

genes like me logo Genes that share pathways with STAT4: view

Pathways by source for STAT4 Gene

4 GeneGo (Thomson Reuters) pathways for STAT4 Gene
  • Immune response IL-12-induced IFN-gamma production
  • Immune response IL-22 signaling pathway
  • Immune response IL-23 signaling pathway
  • Immune response_IL-12 signaling pathway
12 Qiagen pathways for STAT4 Gene
  • CNTF Signaling
  • ErbB2-ErbB3 Heterodimers
  • FLT3 Signaling
  • GPCR Pathway
  • IL-3 Pathway
1 Cell Signaling Technology pathway for STAT4 Gene

SIGNOR curated interactions for STAT4 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for STAT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006952 defense response IBA 21873635
GO:0007165 signal transduction IEA --
GO:0007259 JAK-STAT cascade IBA 21873635
GO:0019221 cytokine-mediated signaling pathway IEA,TAS --
genes like me logo Genes that share ontologies with STAT4: view

Drugs & Compounds for STAT4 Gene

(5) Drugs for STAT4 Gene - From: PharmGKB, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Etanercept Approved, Investigational Pharma 454
Lisofylline Investigational Pharma 3

(4) Additional Compounds for STAT4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with STAT4: view

Transcripts for STAT4 Gene

mRNA/cDNA for STAT4 Gene

2 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STAT4

Alternative Splicing Database (ASD) splice patterns (SP) for STAT4 Gene

No ASD Table

Relevant External Links for STAT4 Gene

GeneLoc Exon Structure for
STAT4

Expression for STAT4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for STAT4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for STAT4 Gene

This gene is overexpressed in Whole Blood (x5.6) and Brain - Cortex (x4.3).

Protein differential expression in normal tissues from HIPED for STAT4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.0), CD8 Tcells (15.2), Lymph node (9.4), and NK cells (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for STAT4 Gene



Protein tissue co-expression partners for STAT4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for STAT4

SOURCE GeneReport for Unigene cluster for STAT4 Gene:

Hs.80642

Evidence on tissue expression from TISSUES for STAT4 Gene

  • Nervous system(3.8)
  • Blood(3.7)
  • Lymph node(3.1)
  • Spleen(3.1)
  • Intestine(2.8)
  • Bone marrow(2.7)
  • Heart(2.6)
  • Pancreas(2.5)
  • Skin(2.4)
  • Eye(2.4)
  • Muscle(2.4)
  • Thyroid gland(2.3)
  • Liver(2.2)
  • Kidney(2.2)
  • Lung(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for STAT4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • skull
  • tooth
Thorax:
  • esophagus
Abdomen:
  • intestine
  • large intestine
  • small intestine
  • stomach
Pelvis:
  • penis
  • testicle
  • vagina
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with STAT4: view

No data available for mRNA Expression by UniProt/SwissProt for STAT4 Gene

Orthologs for STAT4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for STAT4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia STAT4 30
  • 99.73 (n)
Cow
(Bos Taurus)
Mammalia STAT4 30 31
  • 91.89 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia STAT4 30
  • 91.8 (n)
Oppossum
(Monodelphis domestica)
Mammalia STAT4 31
  • 90 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Stat4 30 17 31
  • 88.37 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Stat4 30
  • 88.24 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia STAT4 31
  • 75 (a)
OneToOne
Chicken
(Gallus gallus)
Aves STAT4 30 31
  • 80.04 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia stat4 30
  • 69.75 (n)
Zebrafish
(Danio rerio)
Actinopterygii stat4 30 31
  • 64.55 (n)
OneToOne
Species where no ortholog for STAT4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for STAT4 Gene

ENSEMBL:
Gene Tree for STAT4 (if available)
TreeFam:
Gene Tree for STAT4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for STAT4: view image

Paralogs for STAT4 Gene

Paralogs for STAT4 Gene

(8) SIMAP similar genes for STAT4 Gene using alignment to 9 proteins:

  • STAT4_HUMAN
  • B7SIX5_HUMAN
  • C9JFG0_HUMAN
  • C9JM11_HUMAN
  • D3DPI9_HUMAN
  • E9PBE2_HUMAN
  • E9PG69_HUMAN
  • Q53RU2_HUMAN
  • Q53S87_HUMAN
genes like me logo Genes that share paralogs with STAT4: view

Variants for STAT4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for STAT4 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
708166 Benign: not provided 191,036,258(-) A/G SYNONYMOUS_VARIANT
712050 Likely Benign: not provided 191,069,730(-) G/A SYNONYMOUS_VARIANT
714164 Benign: not provided 191,148,090(-) A/G SYNONYMOUS_VARIANT
715628 Benign: not provided 191,039,295(-) G/T SYNONYMOUS_VARIANT
719170 Likely Benign: not provided 191,062,887(-) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for STAT4 Gene

Structural Variations from Database of Genomic Variants (DGV) for STAT4 Gene

Variant ID Type Subtype PubMed ID
esv25901 CNV loss 19812545
esv2657029 CNV deletion 23128226
esv2676475 CNV deletion 23128226
esv2721278 CNV deletion 23290073
esv2721279 CNV deletion 23290073
esv2721280 CNV deletion 23290073
esv3560730 CNV deletion 23714750
esv3593761 CNV loss 21293372
esv3593762 CNV gain 21293372
nsv1133282 CNV tandem duplication 24896259
nsv834493 CNV gain 17160897
nsv999391 CNV gain 25217958

Variation tolerance for STAT4 Gene

Residual Variation Intolerance Score: 31% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.09; 22.21% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for STAT4 Gene

Human Gene Mutation Database (HGMD)
STAT4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
STAT4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for STAT4 Gene

Disorders for STAT4 Gene

MalaCards: The human disease database

(23) MalaCards diseases for STAT4 Gene - From: OMIM, ClinVar, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
systemic lupus erythematosus 11
  • systemic lupus erythematosus, susceptibility to, 11
systemic lupus erythematosus
  • sle
lupus erythematosus
  • systemic lupus erythematosus
pediatric systemic lupus erythematosus
  • sle, pediatric onset
behcet syndrome
  • behcet disease; bd
- elite association - COSMIC cancer census association via MalaCards
Search STAT4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

STAT4_HUMAN
  • Systemic lupus erythematosus 11 (SLEB11) [MIM:612253]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269 PubMed:17804842, ECO:0000269 PubMed:19109131}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269 PubMed:17804842}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for STAT4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with STAT4: view

No data available for Genatlas for STAT4 Gene

Publications for STAT4 Gene

  1. Genetic risk factors in lupus nephritis and IgA nephropathy--no support of an overlap. (PMID: 20479942) Vuong MT … Padyukov L (PloS one 2010) 3 23 41
  2. Influence of STAT4 polymorphism in primary Sjögren's syndrome. (PMID: 20360187) Palomino-Morales RJ … Martín J (The Journal of rheumatology 2010) 3 23 41
  3. STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: a replication study. (PMID: 20153791) Diaz-Gallo LM … Martin J (Human immunology 2010) 3 23 41
  4. A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus. (PMID: 20169389) Yuan H … Ye DQ (Modern rheumatology 2010) 3 23 41
  5. Polymorphisms of signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) contribute to progression of childhood IgA nephropathy. (PMID: 20045654) Hahn WH … Kim SD (Cytokine 2010) 3 23 41

Products for STAT4 Gene

  • Addgene plasmids for STAT4

Sources for STAT4 Gene