STAT4

Summary

STAT4 (signal transducer and activator of transcription 4, HGNC:11365) is a protein-coding gene on chromosome 2q32.2-q32.3, encoding Signal transducer and activator of transcription 4 (Q14765). Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.

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.

Source: NCBI Gene 6775 — RefSeq curated summary.

At a glance

• Gene–disease (curated): disabling pansclerotic morphea of childhood (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 94
• Clinical variants (ClinVar): 531 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 193
• Druggable target: yes
• Transcription factor: yes — 33 downstream targets (CollecTRI)
• MANE Select transcript: NM_003151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11365
Approved symbol	STAT4
Name	signal transducer and activator of transcription 4
Location	2q32.2-q32.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138378
Ensembl biotype	protein_coding
OMIM	600558
Entrez	6775

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000358470, ENST00000392320, ENST00000409995, ENST00000413064, ENST00000432798, ENST00000450994, ENST00000463951, ENST00000470708, ENST00000495326, ENST00000495849, ENST00000647167, ENST00000714286, ENST00000714287, ENST00000714288, ENST00000714335, ENST00000714336, ENST00000960212, ENST00000960213, ENST00000960214, ENST00000960215, ENST00000960216, ENST00000960217, ENST00000960218

RefSeq mRNA: 2 — MANE Select: NM_003151 NM_001243835, NM_003151

CCDS: CCDS2310

Canonical transcript exons

ENST00000392320 — 24 exons

Exon	Start	End
ENSE00001372547	191029576	191029866
ENSE00001616842	191030972	191031080
ENSE00001788358	191031450	191031516
ENSE00001845053	191150947	191150994
ENSE00003459083	191054490	191054534
ENSE00003481696	191073098	191073190
ENSE00003487965	191033490	191033626
ENSE00003497169	191069693	191069771
ENSE00003498179	191032958	191033149
ENSE00003516088	191041065	191041148
ENSE00003523522	191034548	191034597
ENSE00003543489	191036164	191036299
ENSE00003563758	191148076	191148204
ENSE00003581307	191039199	191039297
ENSE00003584777	191062762	191062920
ENSE00003591717	191033911	191034005
ENSE00003601043	191061729	191061821
ENSE00003603366	191064807	191064958
ENSE00003610045	191058202	191058219
ENSE00003640858	191146613	191146757
ENSE00003652296	191066430	191066515
ENSE00003684846	191058018	191058111
ENSE00003688547	191058710	191058769
ENSE00003788940	191076227	191076325

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.60.

FANTOM5 (CAGE): breadth broad, TPM avg 10.9745 / max 558.7582, expressed in 734 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32938	6.7085	515
32939	3.1743	477
32937	0.6096	103
32936	0.2539	69
32935	0.0879	38
32931	0.0743	25
32930	0.0374	9
32941	0.0113	3
32940	0.0099	3
32942	0.0074	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.60	gold quality
sperm	CL:0000019	93.37	gold quality
middle temporal gyrus	UBERON:0002771	93.17	gold quality
male germ cell	CL:0000015	91.69	gold quality
blood	UBERON:0000178	90.24	gold quality
right atrium auricular region	UBERON:0006631	89.56	gold quality
cardiac atrium	UBERON:0002081	89.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.85	gold quality
left testis	UBERON:0004533	88.26	gold quality
right testis	UBERON:0004534	88.23	gold quality
pituitary gland	UBERON:0000007	87.71	gold quality
right frontal lobe	UBERON:0002810	87.04	gold quality
spleen	UBERON:0002106	86.78	gold quality
adenohypophysis	UBERON:0002196	86.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.52	gold quality
testis	UBERON:0000473	85.83	gold quality
Brodmann (1909) area 10	UBERON:0013541	85.77	gold quality
lymph node	UBERON:0000029	85.39	gold quality
primary visual cortex	UBERON:0002436	85.13	gold quality
prefrontal cortex	UBERON:0000451	85.10	gold quality
right lobe of liver	UBERON:0001114	84.86	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.51	gold quality
frontal cortex	UBERON:0001870	84.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.39	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.03	gold quality
bone marrow cell	CL:0002092	83.02	gold quality
neocortex	UBERON:0001950	82.59	gold quality
vermiform appendix	UBERON:0001154	81.84	gold quality
colonic epithelium	UBERON:0000397	81.53	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	29.69
E-MTAB-6678	yes	27.01
E-CURD-46	yes	20.91
E-MTAB-9067	yes	4.78
E-CURD-112	yes	3.41
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

33 targets.

Target	Regulation
AKT1
CD4	Activation
CD8A	Activation
CREBBP
CSF2	Activation
FATE1
FCGRT
HAND1
IFNA1
IFNG	Unknown
IL10	Activation
IL12B
IL12RB2	Activation
IL13	Unknown
IL17A	Unknown
IL21	Activation
IL2RA	Unknown
IRF1	Unknown
IRF4
LTA	Repression
MYC	Activation
NOS2	Activation
NOX1	Unknown
NOX4	Unknown
PIK3R1
PIM1	Unknown
PRF1	Activation
PRKCQ
S100A4	Activation
SOCS3	Repression

Upstream regulators (CollecTRI, top): CREB1, DNMT3A, GATA3, NFKB1, NFKB, PITX2, POU2F1, REL, RELA, SMAD3, SP1, STAT4, STAT6, TBX21

miRNA regulators (miRDB)

23 targeting STAT4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-4704-3P	98.28	69.33	1300

Literature-anchored findings (GeneRIF, showing 40)

• STAT4 regulates IL-12-induced expression of the perforin gene in NK cells (PMID:12372421)
• Active STAT4, essential for IL-12-mediated Th1 differentiation, is readily detectable in biopsies from Peyer’s patches and ileal mucosa, and STAT4-DNA binding activity is demonstrable by electrophoretic mobility-shift assay of lamina propria lymphocytes. (PMID:12496413)
• STAT4 is constitutively activated in Crohn’s patients but not in healthy volunteers (PMID:12615922)
• STAT4 is repressed by PIASx (PMID:12716907)
• requires the N-terminal domain for efficient phosphorylation (PMID:12805384)
• STAT4 signaling in human vascular endothelial cells is activated by interferon alpha but not by IL-12 (PMID:15087447)
• The STAT4 is transactivated by Ikaros (Ik) and Ik binding elements were revealed in its promoter. (PMID:16081070)
• identify and characterize the transcriptional regulatory elements in the promoter region of the human STAT4 gene. (PMID:16301617)
• these results indicate that STAT-4 can be finely tuned along with DC maturation through NF-kappaB activation and that its induction may be involved in preparing the DC to be receptive to the cytokine environment present in lymphoid organs. (PMID:17046972)
• IFNAR2 cytoplasmic domain serves to link STAT4 to the IFNAR as a pre-assembled complex that facilitates cytokine-driven STAT4 activation. (PMID:17095088)
• STAT-4 T90089C polymorphism might be the genetic factor for the risk of asthma in the Chinese population (PMID:17532201)
• A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. (PMID:17804842)
• A haplotype of the STAT4 gene shows consistent association with rheumatoid arthritis susceptibility across Whites and Asians. (PMID:17932559)
• Single nucleotide polymorphisms in the STAT4 gene are associated with primary Sjogren’s syndrome. (PMID:18273036)
• STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians. (PMID:18432273)
• STAT4 and the TRAF1/C5 loci are associated with rheumatoid arthritis susceptibility. (PMID:18434327)
• STAT4 contributes to the phenotypic heterogeneity of systemic lupus erythematosus, predisposing specifically to more severe disease. (PMID:18516230)
• We conclude that STAT4 is associated with RA and SLE in the Japanese. (PMID:18576330)
• Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data. (PMID:18576336)
• The SNP rs7582694 in STAT4 displayed a increased risk of systemic lupus erythematosus with two independent risk alleles of the IRF5. (PMID:18579578)
• study concludes that mutant alleles or genotypes of both TRAF1 and STAT4 polymorphisms are associated with the development of Rheumatoid arthritis in our population. (PMID:18625278)
• in a genetically homogeneous population, the STAT4 rs7574865 G/T polymorphism, which has been shown to be associated with several autoimmune diseases, is associated with susceptibility to type 1 diabetes (T1D) (PMID:18703106)
• The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin and described for the first time in both clinical forms of inflammatory bowel disease, Crohn’s disease, ulcerative colitis and type 1 diabetes mellitus. (PMID:18759272)
• T helper (Th) type 1 cells expressing transgenic STAT4 beta (an isoform lacking the C-terminal transactivation domain) secrete significantly more tumor necrosis factor-alpha upon T cell receptor stimulation than transgenic STAT4alpha-expressing Th1 cells. (PMID:18802110)
• The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. (PMID:18803832)
• Data confirm STAT4 as a susceptibility gene for systemic lupus erythematosus and suggest the presence of at least two functional variants affecting levels of STAT4 and also indicate that the genes STAT4 and IRF5 act additively to increase the risk for SLE (PMID:19019891)
• Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogren’s syndrome are reported. (PMID:19092842)
• The risk allele of STAT4 is associated with increased sensitivity to IFN-alpha signaling in systemic lupus erythematosus. (PMID:19109131)
• The age at diagnosis is lowest in the patients carrying the homozygotes of a minor allele, middle in the heterozygotes, and highest in the homozygotes of a major allele, suggesting the dosage effects of risk alleles on the age of onset of disease. (PMID:19120275)
• Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE (PMID:19225526)
• Genetic polymorphisms in the Jak-Stat signaling pathway are associated with an increased risk of new cardiovascular events in incident dialysis patients. (PMID:19282076)
• STAT4 influences the genetic predisposition to systemic sclerosis phenotype. (PMID:19286670)
• Our results do not support a major role of the STAT4 rs7574865 gene polymorphism in susceptibility to or clinical manifestations of giant cell arteritis. (PMID:19332627)
• STAT4 is likely to be a crucial component in systemic lupus erythematosus pathogenesis in multiple racial groups (PMID:19333953)
• STAT4 is required for optimal human Th1 lineage development (PMID:19359411)
• Focusing on how STAT4 work in concert with other transcription factors will hopefully provide a better mechanistic understanding of the pathogenesis of various autoimmune diseases. (PMID:19362457)
• STAT4 is not associated with type 2 diabetes in the genetically homogeneous population of Crete. (PMID:19371230)
• Our results replicate and firmly establish the association of STAT4 and CTLA4 with RA and provide highly suggestive evidence for IL2/IL21 loci as a risk factor for RA. (PMID:19404967)
• The results of this meta-analysis demonstrated that STAT4 rs7574865 single nucleotide polymorphism is significantly associated with rheumatoid arthritis and systemic lupus erythematosus. (PMID:19479340)
• single nucleotide polymorphism is associated with psoriasis in population of Crete, Greece (PMID:19500629)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stat4	ENSDARG00000028731
mus_musculus	Stat4	ENSMUSG00000062939
caenorhabditis_elegans		WBGENE00010251
caenorhabditis_elegans		WBGENE00013111

Paralogs (6): STAT1 (ENSG00000115415), STAT5A (ENSG00000126561), STAT6 (ENSG00000166888), STAT3 (ENSG00000168610), STAT2 (ENSG00000170581), STAT5B (ENSG00000173757)

Protein

Protein identifiers

Signal transducer and activator of transcription 4 — Q14765 (reviewed: Q14765)

All UniProt accessions (8): Q14765, A0A2R8Y693, A0AAQ5BHR1, A0AAQ5BHW3, C9JFG0, C9JM11, E9PBE2, E9PG69

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response. Plays a key role in the differentiation of T-helper 1 cells and the production of interferon-gamma. Also participates in multiple neutrophil functions including chemotaxis and production of the neutrophil extracellular traps. After IL12 binding to its receptor IL12RB2, STAT4 interacts with the intracellular domain of IL12RB2 and becomes tyrosine phosphorylated. Phosphorylated STAT4 then homodimerizes and migrates to the nucleus where it can recognize STAT target sequences present in IL12 responsive genes. Although IL12 appears to be the predominant activating signal, STAT4 can also be phosphorylated and activated in response to IFN-gamma stimulation via JAK1 and TYK2 and in response to different interleukins including IL23, IL2 and IL35. Transcription activation of IFN-gamma gene is mediated by interaction with JUN that forms a complex that efficiently interacts with the AP-1-related sequence of the IFN-gamma promoter. In response to IFN-alpha/beta signaling, acts as a transcriptional repressor and suppresses IL5 and IL13 mRNA expression during response to T-cell receptor (TCR) activation.

Subunit / interactions. Forms a homodimer or a heterodimer with a related family member. Interacts with ARL2BP. The SH2 domain interacts, in vitro, with IL12RB2 via a short cytoplasmic domain. Interacts with STAT1. Interacts with JUN; this complex efficiently interacts with the AP-1-related sequence of the IFN-gamma.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Acetylation at Lys-667 is required for JAK2-mediated phosphorylation and activation of STAT4. Tyrosine phosphorylated upon IL12 and IFN-alpha activation, but not by IFN-gamma in T-lymphocytes and NK cells. Serine phosphorylation is required for maximal transcriptional activity but not for DNA binding. Phosphorylation by MAP2K6 at Ser-721 is required for full transcriptional activity induced by IL12. However this serine phosphorylation is not required for cell proliferation although critical for IFN-gamma production.

Disease relevance. 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. Disease susceptibility is associated with variants 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Disabling pansclerotic morphea of childhood (DPMC) [MIM:620443] An autosomal dominant, severe systemic inflammatory disorder that is part of the juvenile localized scleroderma spectrum. DPMC is characterized by poor wound healing with rapidly progressive deep fibrosis involving the mucous membranes, dermis, subcutaneous fat, fascia, muscles, and bone, leading to contractures, musculoskeletal atrophy, and articular ankylosis. Systemic manifestations include cytopenias and hypogammaglobulinemia, but scleroderma-associated autoantibodies are usually not present. The disorder is associated with high morbidity and mortality due to squamous-cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the transcription factor STAT family.

RefSeq proteins (2): NP_001230764, NP_003142* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001217	STAT	Family
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR012345	STAT_TF_DNA-bd_N	Homologous_superfamily
IPR013799	STAT_TF_prot_interaction	Domain
IPR013800	STAT_TF_alpha	Domain
IPR013801	STAT_TF_DNA-bd	Domain
IPR015988	STAT_TF_CC	Homologous_superfamily
IPR029839	STAT4_DBD	Domain
IPR035856	STAT4_SH2	Domain
IPR036535	STAT_N_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR046991	STAT4_CC	Domain
IPR048988	STAT_linker	Domain

Pfam: PF00017, PF01017, PF02864, PF02865, PF21354

UniProt features (14 total): sequence variant 6, modified residue 3, mutagenesis site 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14765-F1	86.87	0.65

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 (3): 667, 693, 721

Mutagenesis-validated functional residues (2):

Position	Phenotype
693	abrogates phosphorylation and transcriptional activity.
721	about 50% loss of transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-8854691	Interleukin-20 family signaling
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-8984722	Interleukin-35 Signalling
R-HSA-9020591	Interleukin-12 signaling
R-HSA-9020933	Interleukin-23 signaling
R-HSA-9020958	Interleukin-21 signaling
R-HSA-9942503	Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-451927	Interleukin-2 family signaling

MSigDB gene sets: 696 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, AGGAAGC_MIR5163P, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, LU_IL4_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_45, MODULE_64, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, NIKOLSKY_OVERCONNECTED_IN_BREAST_CANCER, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (13): regulation of transcription by RNA polymerase II (GO:0006357), defense response (GO:0006952), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cytokine-mediated signaling pathway (GO:0019221), interleukin-12-mediated signaling pathway (GO:0035722), regulation of cell population proliferation (GO:0042127), response to peptide hormone (GO:0043434), T-helper 1 cell differentiation (GO:0045063), positive regulation of transcription by RNA polymerase II (GO:0045944), response to interleukin-6 (GO:0070741), regulation of DNA-templated transcription (GO:0006355), immune response (GO:0006955), signal transduction (GO:0007165)

GO Molecular Function (6): 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 factor activity (GO:0003700), identical protein binding (GO:0042802), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), nuclear body (GO:0016604), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Signaling by Interleukins	3
Interleukin-12 family signaling	3
Interleukin-12 signaling	1
Interleukin-2 family signaling	1
Differentiation of T cells	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of cellular process	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
intracellular membraneless organelle	2
response to stress	1
cell surface receptor signaling pathway via STAT	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-12	1
cell population proliferation	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
alpha-beta T cell activation involved in immune response	1
T cell differentiation involved in immune response	1
T-helper 1 type immune response	1
T-helper cell differentiation	1
positive regulation of DNA-templated transcription	1
response to cytokine	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
protein binding	1
nucleic acid binding	1
binding	1

Protein interactions and networks

STRING

2286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAT4	IL12RB2	Q99665	923
STAT4	IFNG	P01579	917
STAT4	IL12RB1	P42701	901
STAT4	TYK2	P29597	900
STAT4	STAT1	P42224	888
STAT4	TBX21	Q9UL17	885
STAT4	IRF5	Q13568	860
STAT4	IFNAR1	P17181	856
STAT4	IL6	P05231	845
STAT4	JAK1	P23458	845
STAT4	IL23R	Q5VWK5	822
STAT4	PTPN22	Q9Y2R2	819
STAT4	CD4	P01730	808
STAT4	GATA3	P23771	799
STAT4	IL18	Q14116	788

IntAct

49 interactions, top by confidence:

A	B	Type	Score
STAT4	STAT4	psi-mi:“MI:0407”(direct interaction)	0.560
KLF11	STAT4	psi-mi:“MI:0915”(physical association)	0.560
STAT4	NUP58	psi-mi:“MI:0915”(physical association)	0.560
STAT4	STAT1	psi-mi:“MI:0915”(physical association)	0.540
P/V/C	STAT1	psi-mi:“MI:0914”(association)	0.530
STAT4	IL12RB2	psi-mi:“MI:0914”(association)	0.530
STAT4		psi-mi:“MI:0915”(physical association)	0.500
	STAT3	psi-mi:“MI:0914”(association)	0.500
SH2D1B	STAT4	psi-mi:“MI:0915”(physical association)	0.490
CRK	STAT4	psi-mi:“MI:0915”(physical association)	0.490
STAT4	SH2D1B	psi-mi:“MI:0915”(physical association)	0.490
NMI	STAT4	psi-mi:“MI:0915”(physical association)	0.400
STAT4	LAMTOR5	psi-mi:“MI:0915”(physical association)	0.400
	STAT4	psi-mi:“MI:0915”(physical association)	0.400
STAT4	Kdm5a	psi-mi:“MI:0914”(association)	0.350
P/V/C	BCAS2	psi-mi:“MI:0914”(association)	0.350
STAT4	FLOT1	psi-mi:“MI:0914”(association)	0.350
ZNF136	STAT4	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): STAT4 (Co-fractionation), STAT4 (Two-hybrid), STAT4 (Two-hybrid), STAT4 (Affinity Capture-Western), STAT4 (Reconstituted Complex), STAT4 (Affinity Capture-Western), STAT4 (Affinity Capture-Western), STAT4 (Affinity Capture-MS), STAT1 (Affinity Capture-MS), IL12RB2 (Protein-peptide), STAT4 (Affinity Capture-MS), STAT1 (Proximity Label-MS), KMT2D (Proximity Label-MS), SEC16A (Proximity Label-MS), SEC24A (Proximity Label-MS)

ESM2 similar proteins: A2AF47, A2AHJ4, O14795, O46469, O54828, O75916, O94810, P16258, P22059, P31266, P42228, P49805, Q06330, Q14765, Q2M146, Q2TAF4, Q3B7Z2, Q3SZ41, Q4QR86, Q5JSL3, Q5PNP1, Q5R8B7, Q5RFK6, Q5RHQ8, Q5U4W6, Q5ZL23, Q62717, Q62739, Q62769, Q6GLR7, Q6NXD8, Q6PCM2, Q80TJ1, Q80ZD1, Q86UW7, Q8BYR5, Q8BZN6, Q8K394, Q91880, Q91WS7

Diamond homologs: B5X561, Q14765, Q56XZ1, Q764M5, O02799, P40763, P42224, P42225, P42227, P42228, P52630, P52631, P61635, Q19S50, Q6DV79, Q7ZXK3, Q9PVX8, Q9WVL2, P42229, P42230, P42231, P42232, P51692, P52632, Q62771, Q95115, Q9TUM3, Q9TUZ0, Q9TUZ1, Q24151, Q54BD4, O00910, Q70GP4, P42226, P52633, Q61AP6, Q7QDU4, Q9NAD6

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
JAK2	up-regulates	STAT4	phosphorylation
MAPK14	up-regulates	STAT4	phosphorylation
STAT4	“up-regulates quantity by expression”	PRF1	“transcriptional regulation”
STAT4	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
STAT4	“up-regulates activity”	LAMTOR5	binding
TYK2	“up-regulates activity”	STAT4	phosphorylation
IL12A	“up-regulates activity”	STAT4	binding
STAT4	“up-regulates activity”	IFNG	“transcriptional regulation”
IL23R	up-regulates	STAT4
MAP2K6	“up-regulates activity”	STAT4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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:

Pathway	Partners	Fold	FDR
Diseases of signal transduction by growth factor receptors and second messengers	5	16.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of gene expression	5	10.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	229
Likely benign	250
Benign	22

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2572048	NM_003151.4(STAT4):c.1867C>T (p.His623Tyr)	Pathogenic
2572046	NM_003151.4(STAT4):c.1904C>T (p.Ala635Val)	Likely pathogenic

SpliceAI

3942 predictions. Top by Δscore:

Variant	Effect	Δscore
2:191032956:A:C	donor_gain	1.0000
2:191033147:CCCCT:C	acceptor_gain	1.0000
2:191033148:CCCT:C	acceptor_gain	1.0000
2:191033151:T:C	acceptor_gain	1.0000
2:191033489:CCA:C	donor_gain	1.0000
2:191033904:AACTT:A	donor_loss	1.0000
2:191033905:ACTTA:A	donor_loss	1.0000
2:191033906:CTT:C	donor_loss	1.0000
2:191033907:TTACC:T	donor_loss	1.0000
2:191033908:T:TG	donor_loss	1.0000
2:191033909:A:AC	donor_gain	1.0000
2:191033909:AC:A	donor_gain	1.0000
2:191033909:ACC:A	donor_gain	1.0000
2:191033909:ACCC:A	donor_loss	1.0000
2:191033910:C:CC	donor_gain	1.0000
2:191033910:C:CT	donor_loss	1.0000
2:191033910:CC:C	donor_gain	1.0000
2:191033910:CCC:C	donor_gain	1.0000
2:191033910:CCCAT:C	donor_gain	1.0000
2:191034001:TGTTC:T	acceptor_gain	1.0000
2:191034004:TC:T	acceptor_gain	1.0000
2:191034004:TCCT:T	acceptor_loss	1.0000
2:191034005:CC:C	acceptor_gain	1.0000
2:191034006:CTA:C	acceptor_loss	1.0000
2:191034007:T:A	acceptor_loss	1.0000
2:191034010:A:T	acceptor_gain	1.0000
2:191036158:TCTCA:T	donor_loss	1.0000
2:191036159:CTCA:C	donor_loss	1.0000
2:191036160:TCA:T	donor_loss	1.0000
2:191036161:CA:C	donor_loss	1.0000

AlphaMissense

4973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:191033511:A:G	W611R	1.000
2:191033511:A:T	W611R	1.000
2:191033546:A:G	F599S	1.000
2:191033549:C:G	R598T	1.000
2:191033557:A:C	F595L	1.000
2:191033557:A:T	F595L	1.000
2:191033558:A:G	F595S	1.000
2:191033559:A:G	F595L	1.000
2:191033582:A:G	L587P	1.000
2:191033611:A:C	F577L	1.000
2:191033611:A:T	F577L	1.000
2:191033612:A:G	F577S	1.000
2:191033613:A:G	F577L	1.000
2:191033616:C:G	G576R	1.000
2:191033921:A:G	W569R	1.000
2:191033921:A:T	W569R	1.000
2:191061758:T:A	K335N	1.000
2:191061758:T:G	K335N	1.000
2:191148077:A:G	W43R	1.000
2:191148077:A:T	W43R	1.000
2:191032990:A:G	F671S	0.999
2:191033001:T:A	K667N	0.999
2:191033001:T:G	K667N	0.999
2:191033020:A:G	L661P	0.999
2:191033029:A:G	L658P	0.999
2:191033029:A:T	L658Q	0.999
2:191033122:G:T	P627H	0.999
2:191033542:A:C	S600R	0.999
2:191033542:A:T	S600R	0.999
2:191033543:C:A	S600I	0.999

dbSNP variants (sampled 300 via entrez): RS1000005308 (2:191075354 A>G), RS1000019127 (2:191214760 C>T), RS1000042334 (2:191136489 C>T), RS1000056234 (2:191053845 C>T), RS1000062838 (2:191127406 C>A), RS1000093706 (2:191164667 C>G), RS1000096258 (2:191032357 T>G), RS1000098164 (2:191074968 C>A), RS1000108923 (2:191099266 G>A), RS1000126035 (2:191081697 T>C), RS1000132287 (2:191086366 T>A), RS1000137003 (2:191133922 A>C), RS1000174011 (2:191081330 G>T), RS1000184936 (2:191168129 C>T), RS1000195559 (2:191210787 C>G,T)

Disease associations

OMIM: gene MIM:600558 | disease phenotypes: MIM:612253, MIM:620443

GenCC curated gene-disease

Disease	Classification	Inheritance
disabling pansclerotic morphea of childhood	Strong	Autosomal dominant
systemic lupus erythematosus	Supportive	Unknown

Mondo (3): systemic lupus erythematosus, susceptibility to, 11 (MONDO:0012835), disabling pansclerotic morphea of childhood (MONDO:0957497), systemic lupus erythematosus (MONDO:0007915)

Orphanet (0):

HPO phenotypes

193 total (30 of 193 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000031	Epididymitis
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000100	Nephrotic syndrome
HP:0000123	Nephritis
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000554	Uveitis
HP:0000572	Visual loss
HP:0000585	Band keratopathy
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000737	Irritability
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000951	Abnormality of the skin
HP:0000969	Edema
HP:0000988	Skin rash
HP:0000992	Cutaneous photosensitivity
HP:0001061	Acne
HP:0001094	Iridocyclitis

GWAS associations

94 associations (top):

Study	Trait	p-value
GCST000144_5	Systemic lupus erythematosus	9.000000e-14
GCST000216_8	Systemic lupus erythematosus	8.000000e-11
GCST000507_11	Systemic lupus erythematosus	5.000000e-42
GCST000650_3	Systemic sclerosis	3.000000e-09
GCST000677_2	Rheumatoid arthritis	2.000000e-06
GCST000987_9	Celiac disease or Rheumatoid arthritis	4.000000e-10
GCST000996_2	Systemic lupus erythematosus	2.000000e-20
GCST000996_6	Systemic lupus erythematosus	8.000000e-06
GCST001010_12	Primary biliary cholangitis	2.000000e-19
GCST001146_1	Systemic sclerosis	2.000000e-13
GCST001160_2	Systemic sclerosis	9.000000e-08
GCST001277_21	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-11
GCST001685_3	Primary biliary cholangitis	1.000000e-06
GCST001708_1	Systemic lupus erythematosus	4.000000e-14
GCST001725_73	Inflammatory bowel disease	3.000000e-11
GCST001768_2	Behcet’s disease	6.000000e-09
GCST001768_3	Behcet’s disease	4.000000e-08
GCST001775_2	Hepatocellular carcinoma in hepatitis B infection	2.000000e-10
GCST001795_19	Systemic lupus erythematosus	1.000000e-21
GCST001804_2	Behcet’s disease	1.000000e-09
GCST002069_10	Systemic lupus erythematosus and Systemic sclerosis	3.000000e-11
GCST002217_2	Sjögren’s syndrome	2.000000e-17
GCST002318_44	Rheumatoid arthritis	1.000000e-12
GCST002318_45	Rheumatoid arthritis	2.000000e-08
GCST002318_60	Rheumatoid arthritis	4.000000e-19
GCST002463_12	Systemic lupus erythematosus	5.000000e-09
GCST003103_1	Systemic lupus erythematosus	4.000000e-07
GCST003129_7	Primary biliary cholangitis	2.000000e-14
GCST003155_43	Systemic lupus erythematosus	6.000000e-122
GCST003156_10	Systemic lupus erythematosus	9.000000e-17

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:1001017	limited scleroderma
EFO:0008536	anti-centromere-antibody-positive systemic scleroderma
EFO:0009087	non-typhoidal Salmonella bacteremia
EFO:0009933	Thyroid preparation use measurement
EFO:0004842	eosinophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523296 (SINGLE PROTEIN), CHEMBL4523706 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7574865	Efficacy	3	etanercept	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7574865	STAT4	3	2.50	1	etanercept

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.44	IC50	360	nM	CHEMBL6144023
6.00	Kd	1000	nM	CHEMBL4452527
5.96	IC50	1100	nM	CHEMBL4452527

PubChem BioAssay actives

2 with measured affinity, of 13 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[[2-[[(5S,8S,10aR)-8-[[(2S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl]carbamoyl]-3-[8-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]oct-7-ynoyl]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl]-1H-indol-5-yl]-difluoromethyl]phosphonic acid	1559101: Binding affinity to recombinant human His/SUMO-tagged STAT4 (133 to 705 residues) expressed in Escherichia coli Rosetta (DE3) incubated for 1 hr by fluorescence polarization assay	kd	1.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Benzene	increases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, affects response to substance	3
perfluorooctanoic acid	increases activity, increases expression	2
nickel sulfate	increases expression	2
Arsenic	increases methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression, affects binding, increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
leptomycin B	affects localization	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
arsenic disulfide	decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Allergens	increases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4356793	Binding	Binding affinity to recombinant human His/SUMO-tagged STAT4 (133 to 705 residues) expressed in Escherichia coli Rosetta (DE3) incubated for 1 hr by fluorescence polarization assay	Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein. — J Med Chem

Cellosaurus cell lines

11 cell lines: 5 cancer cell line, 3 embryonic stem cell, 2 transformed cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6U5	SEES3-1V human STAT4, clone1	Embryonic stem cell	Male
CVCL_A6U6	SEES3-1V human STAT4, clone2	Embryonic stem cell	Male
CVCL_A6U7	SEES3-1V human STAT4, clone3	Embryonic stem cell	Male
CVCL_B7ZM	Abcam Raji STAT4 KO	Cancer cell line	Male
CVCL_C0AF	Abcam THP-1 STAT4 KO	Cancer cell line	Male
CVCL_C3KJ	N/Tert-1 STAT4	Telomerase immortalized cell line	Male
CVCL_C7C3	Abcam PC-3 STAT4 KO	Cancer cell line	Male
CVCL_D8BL	Ubigene A-549 STAT4 KO	Cancer cell line	Male
CVCL_D8WG	Ubigene HCT 116 STAT4 KO	Cancer cell line	Male
CVCL_D9T9	Ubigene HEK293 STAT4 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients