STAT3 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human STAT3 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene STAT3, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene STAT3, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene STAT3 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene STAT3 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene STAT3, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene STAT3, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene STAT3, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene STAT3 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene STAT3, summarize transcription factor regulatory data. If STAT3 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate STAT3 — names with evidence type (ChIP-seq / predicted / experimentally validated) If STAT3 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene STAT3 protein as a drug target, summarize pharmacology data. If STAT3 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If STAT3 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene STAT3, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene STAT3, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in STAT3: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor and central hub of JAK-STAT signaling, activated downstream of cytokines, growth factors, and oncogenic kinases; its importance spans immunity, development, and cancer. The gene sits on chromosome 17 (GRCh38: 42,313,324–42,388,568, minus strand) and is virtually ubiquitous, expressed in 301 of 303 profiled tissues with a maximum expression score of 99.31. Dominant-negative or gain-of-function mutations cause two well-characterized Mendelian disorders — autosomal dominant Hyper-IgE syndrome and STAT3-related early-onset multisystem autoimmune disease — and ~839 ClinVar variants have been catalogued. GWAS signals reach genome-wide significance for multiple sclerosis (p = 2.0e-28), inflammatory bowel disease (p = 6.0e-22), and Crohn’s disease (p = 2.0e-15). STAT3 is a VIP pharmacogene in PharmGKB, with over 100 targeting molecules in development; momelotinib, an approved JAK1/JAK2 inhibitor that blocks STAT3 activation, represents the most advanced therapeutic. The protein interacts with ~8,628 partners in STRING, with highest-confidence physical associations to JAK1, JAK2, and SRC.
Gene identifiers
- HGNC ID: HGNC:11364
- Approved symbol: STAT3
- Ensembl gene ID: ENSG00000168610
- NCBI Entrez Gene ID: 6774
- OMIM gene/locus ID: 102582
- Genomic location (GRCh38):
- Chromosome: 17
- Start position: 42,313,324
- End position: 42,388,568
- Strand: − (minus)
Transcript identifiers
Ensembl transcripts (ENST)
Total: 94 transcripts
| ENST ID | Biotype |
|---|---|
| ENST00000264657 | protein_coding |
| ENST00000389272 | protein_coding |
| ENST00000404395 | protein_coding |
| ENST00000462269 | retained_intron |
| ENST00000462286 | protein_coding_CDS_not_defined |
| ENST00000471989 | retained_intron |
| ENST00000478276 | retained_intron |
| ENST00000491272 | protein_coding_CDS_not_defined |
| ENST00000498330 | retained_intron |
| ENST00000585360 | retained_intron |
| ENST00000585517 | protein_coding |
| ENST00000588969 | protein_coding |
| ENST00000590776 | protein_coding_CDS_not_defined |
| ENST00000676636 | nonsense_mediated_decay |
| ENST00000677002 | protein_coding |
| ENST00000677030 | protein_coding |
| ENST00000677152 | protein_coding |
| ENST00000677270 | retained_intron |
| ENST00000677271 | nonsense_mediated_decay |
| ENST00000677308 | nonsense_mediated_decay |
| ENST00000677346 | protein_coding_CDS_not_defined |
| ENST00000677421 | protein_coding |
| ENST00000677442 | protein_coding |
| ENST00000677479 | protein_coding |
| ENST00000677500 | protein_coding_CDS_not_defined |
| ENST00000677603 | protein_coding |
| ENST00000677723 | protein_coding |
| ENST00000677763 | retained_intron |
| ENST00000677820 | nonsense_mediated_decay |
| ENST00000678043 | protein_coding |
| ENST00000678044 | protein_coding |
| ENST00000678048 | protein_coding |
| ENST00000678108 | retained_intron |
| ENST00000678445 | nonsense_mediated_decay |
| ENST00000678529 | retained_intron |
| ENST00000678535 | protein_coding |
| ENST00000678572 | protein_coding |
| ENST00000678659 | retained_intron |
| ENST00000678674 | protein_coding |
| ENST00000678764 | retained_intron |
| ENST00000678792 | protein_coding |
| ENST00000678827 | protein_coding |
| ENST00000678905 | protein_coding |
| ENST00000678906 | protein_coding |
| ENST00000678913 | protein_coding |
| ENST00000678960 | protein_coding |
| ENST00000679014 | protein_coding |
| ENST00000679166 | protein_coding |
| ENST00000679185 | protein_coding |
| ENST00000679231 | retained_intron |
| ENST00000715205 | protein_coding |
| ENST00000858552 | protein_coding |
| ENST00000858553 | protein_coding |
| ENST00000858554 | protein_coding |
| ENST00000858555 | protein_coding |
| ENST00000858556 | protein_coding |
| ENST00000858557 | protein_coding |
| ENST00000858558 | protein_coding |
| ENST00000858559 | protein_coding |
| ENST00000858560 | protein_coding |
| ENST00000858561 | protein_coding |
| ENST00000858562 | protein_coding |
| ENST00000922763 | protein_coding |
| ENST00000922764 | protein_coding |
| ENST00000922765 | protein_coding |
| ENST00000922766 | protein_coding |
| ENST00000922767 | protein_coding |
| ENST00000922768 | protein_coding |
| ENST00000922769 | protein_coding |
| ENST00000922770 | protein_coding |
| ENST00000943782 | protein_coding |
| ENST00000943783 | protein_coding |
| ENST00000943784 | protein_coding |
| ENST00000943785 | protein_coding |
| ENST00000943786 | protein_coding |
| ENST00000943787 | protein_coding |
| ENST00000943788 | protein_coding |
| ENST00000943789 | protein_coding |
| ENST00000943790 | protein_coding |
| ENST00000943791 | protein_coding |
| ENST00000943792 | protein_coding |
| ENST00000943793 | protein_coding |
| ENST00000943794 | protein_coding |
| ENST00000943795 | protein_coding |
| ENST00000943796 | protein_coding |
| ENST00000943797 | protein_coding |
| ENST00000943798 | protein_coding |
| ENST00000943799 | protein_coding |
| ENST00000943800 | protein_coding |
| ENST00000943801 | protein_coding |
| ENST00000943802 | protein_coding |
| ENST00000943803 | protein_coding |
| ENST00000943804 | protein_coding |
| ENST00000943805 | protein_coding |
RefSeq transcripts (Human, NM_ accessions)
Total: 20 mRNA transcripts
| NM Accession | MANE Select |
|---|---|
| NM_139276 | ✓ |
| NM_003150 | |
| NM_001384993 | |
| NM_001384992 | |
| NM_001384991 | |
| NM_001384990 | |
| NM_001384989 | |
| NM_001384988 | |
| NM_001384987 | |
| NM_001384986 | |
| NM_001384985 | |
| NM_001384984 | |
| NM_001369520 | |
| NM_001369519 | |
| NM_001369518 | |
| NM_001369517 | |
| NM_001369516 | |
| NM_001369514 | |
| NM_001369513 | |
| NM_001369512 |
CCDS identifiers
Total: 11 IDs
- CCDS32656
- CCDS32657
- CCDS59288
- CCDS92309
- CCDS92310
- CCDS92311
- CCDS92312
- CCDS92313
- CCDS92314
- CCDS92315
- CCDS92316
Canonical/MANE SELECT transcript exons
Transcript: ENST00000264657 (MANE Select: NM_139276)
Total exons: 24
| Exon ID | Start | End | Coordinates (GRCh38) |
|---|---|---|---|
| ENSE00001835049 | 42313324 | 42315800 | chr17:42313324-42315800 (−) |
| ENSE00002832033 | 42317182 | 42317224 | chr17:42317182-42317224 (−) |
| ENSE00001179541 | 42322282 | 42322494 | chr17:42322282-42322494 (−) |
| ENSE00000950725 | 42323004 | 42323143 | chr17:42323004-42323143 (−) |
| ENSE00003463278 | 42323260 | 42323354 | chr17:42323260-42323354 (−) |
| ENSE00003504262 | 42323573 | 42323625 | chr17:42323573-42323625 (−) |
| ENSE00003534325 | 42324711 | 42324846 | chr17:42324711-42324846 (−) |
| ENSE00003503687 | 42324963 | 42325061 | chr17:42324963-42325061 (−) |
| ENSE00000950720 | 42326116 | 42326199 | chr17:42326116-42326199 (−) |
| ENSE00000950719 | 42329410 | 42329457 | chr17:42329410-42329457 (−) |
| ENSE00001228108 | 42329554 | 42329647 | chr17:42329554-42329647 (−) |
| ENSE00001228116 | 42329747 | 42329776 | chr17:42329747-42329776 (−) |
| ENSE00001228122 | 42331472 | 42331531 | chr17:42331472-42331531 (−) |
| ENSE00001228128 | 42333673 | 42333765 | chr17:42333673-42333765 (−) |
| ENSE00001228134 | 42333891 | 42334049 | chr17:42333891-42334049 (−) |
| ENSE00001228140 | 42337435 | 42337586 | chr17:42337435-42337586 (−) |
| ENSE00001505324 | 42337763 | 42337857 | chr17:42337763-42337857 (−) |
| ENSE00001505325 | 42338731 | 42338812 | chr17:42338731-42338812 (−) |
| ENSE00000725380 | 42339314 | 42339409 | chr17:42339314-42339409 (−) |
| ENSE00003551986 | 42345559 | 42345657 | chr17:42345559-42345657 (−) |
| ENSE00003631188 | 42346569 | 42346713 | chr17:42346569-42346713 (−) |
| ENSE00001302308 | 42348389 | 42348539 | chr17:42348389-42348539 (−) |
| ENSE00003466416 | 42316789 | 42316901 | chr17:42316789-42316901 (−) |
| ENSE00002972150 | 42388279 | 42388442 | chr17:42388279-42388442 (−) |
Protein identifiers
UniProt Accessions
Reviewed (Canonical):
- P40763 – Signal transducer and activator of transcription 3
Unreviewed (Isoforms/Variants):
- A0A7I2V2G1
- A0A7I2V2T1
- A0A7I2V395
- A0A7I2V3V0
- A0A7I2V444
- A0A7I2V4C8
- A0A7I2V4F6
- A0A7I2V4R2
- A0A7I2V4R3
- A0A7I2V552
- A0A7I2V5N9
- A0A7I2YQD2
- A0A7I2YQI1
- A0A7I2YQR5
- G8JLH9
RefSeq Protein Accessions (NP_)
- NP_001356441
- NP_001356442
- NP_001356443
- NP_001356445
- NP_001356446
- NP_001356447
- NP_001356448
- NP_001356449
- NP_001371913
- NP_001371914
- NP_001371915
- NP_001371916
- NP_001371917
- NP_001371918
- NP_001371919
- NP_001371920
- NP_001371921
- NP_001371922
- NP_003141
- NP_644805
Protein Domains and Families
InterPro
| ID | Name | Type |
|---|---|---|
| IPR000980 | SH2 domain | Domain |
| IPR001217 | Transcription factor STAT | Family |
| IPR008967 | p53-like transcription factor, DNA-binding domain superfamily | Homologous superfamily |
| IPR012345 | STAT transcription factor, DNA-binding, N-terminal | Homologous superfamily |
| IPR013799 | STAT transcription factor, protein interaction | Domain |
| IPR013800 | STAT transcription factor, all-alpha domain | Domain |
| IPR013801 | STAT transcription factor, DNA-binding | Domain |
| IPR015988 | STAT transcription factor, coiled coil | Homologous superfamily |
| IPR035855 | STAT3, SH2 domain | Domain |
| IPR036535 | STAT transcription factor, N-terminal domain superfamily | Homologous superfamily |
| IPR036860 | SH2 domain superfamily | Homologous superfamily |
| IPR048988 | Signal transducer and activator of transcription, linker domain | Domain |
Pfam
| ID |
|---|
| PF00017 |
| PF01017 |
| PF02864 |
| PF02865 |
| PF21354 |
SMART
| ID |
|---|
| SM00964 |
CDD (Conserved Domain Database)
| ID |
|---|
| CD10374 |
| CD16847 |
| CD16853 |
Antibody Availability
STAT3 antibodies are available through:
- Human Protein Atlas (HPA) – Antibodies with tissue expression and subcellular localization data
- Cross-referenced in UniProt through BindingDB and related antibody databases
Human Protein Atlas provides multiple validated STAT3 antibodies with immunohistochemistry and immunofluorescence data across human tissues.
Structure
Experimental Structures (PDB)
Total: 6 structures
| PDB ID | Method | Resolution | Description |
|---|---|---|---|
| 5AX3 | X-ray diffraction | 2.984 Å | ERK2 complexed with allosteric and ATP-competitive inhibitors |
| 5U5S | Solution NMR | — | Brd2 second bromodomain in complex with STAT3 peptide |
| 6NJS | X-ray diffraction | 2.7 Å | STAT3 core in complex with compound SD36 |
| 6NUQ | X-ray diffraction | 3.15 Å | STAT3 core in complex with compound SI109 |
| 6QHD | X-ray diffraction | 2.85 Å | Lysine acetylated and tyrosine phosphorylated STAT3 in complex with DNA |
| 6TLC | X-ray diffraction | 2.9 Å | Unphosphorylated human STAT3 in complex with MS3-6 monobody |
Predicted Structures
AlphaFold
- Model ID: P40763
- pLDDT (mean confidence): 85.80
- High-confidence residues (pLDDT > 70): 70%
Cross-species orthologs
| Organism | Gene ID | Gene Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000004040 (Entrez: 20848) | Stat3 |
| Rat (Rattus norvegicus) | ENSRNOG00000019742 (Entrez: 25125) | Stat3 |
| Zebrafish (Danio rerio) | ENSDARG00000022712 (Entrez: 30767) | stat3 |
| Fruit fly (Drosophila melanogaster) | FBGN0016917 (Entrez: 42428) | Stat92E |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
Clinical Variants (ClinVar)
Variant Summary
- Total variants: ~839
- Classification breakdown (from sampled data):
- Pathogenic: ~10
- Likely Pathogenic: ~8
- Uncertain Significance: ~50
- Likely Benign: ~100
- Benign: ~50
- Conflicting classifications: ~3
Top 30 Pathogenic/Likely Pathogenic Variants
| Variant ID | HGVS Notation | Classification | Associated Condition |
|---|---|---|---|
| 1005984 | c.2141C>T (p.Thr714Ile) | Pathogenic | STAT3 gain of function |
| 1012305 | c.1699A>G (p.Asn567Asp) | Likely Pathogenic | Hyper-IgE syndrome |
| 1039785 | c.1228C>T (p.His410Tyr) | Pathogenic | STAT3 deficiency |
| 1068485 | c.1859C>G (p.Thr620Ser) | Pathogenic | Hyper-IgE syndrome |
| 1067042 | c.1182G>A (p.Met394Ile) | Likely Pathogenic | STAT3 deficiency |
| 1067430 | c.1924A>G (p.Lys642Glu) | Likely Pathogenic | Hyper-IgE syndrome |
| 1176687 | c.1177G>T (p.Val393Leu) | Likely Pathogenic | STAT3 deficiency |
| 1398166 | c.1110-2A>G | Pathogenic | Immunodeficiency |
| 1429110 | c.2116C>A (p.Leu706Met) | Pathogenic | Hyper-IgE syndrome |
| 1429145 | c.1915C>G (p.Pro639Ala) | Pathogenic | STAT3 deficiency |
| 144030 | c.1175A>G (p.Lys392Arg) | Pathogenic | Hyper-IgE syndrome |
| 144031 | c.1938C>G (p.Asn646Lys) | Pathogenic | STAT3 deficiency |
| 144032 | c.1974G>C (p.Lys658Asn) | Pathogenic | Hyper-IgE syndrome |
| 1339186 | c.2123C>G (p.Thr708Ser) | Likely Pathogenic | Immunodeficiency |
| 1470407 | c.861G>T (p.Leu287Phe) | Likely Pathogenic | STAT3 deficiency |
| 1701323 | c.994C>T (p.His332Tyr) | Pathogenic/Likely Pathogenic | Hyper-IgE syndrome |
AI-Based Predictions
SpliceAI Predictions
- Total variants with predictions: 3,192
- Effect types: Donor gain/loss, acceptor gain/loss
- Top 30 by predicted impact (highest delta scores):
| Variant | Effect | Score |
|---|---|---|
| 17:42316787:AC:A | Donor gain | 0.99 |
| 17:42317180:A:AC | Donor gain | 1.00 |
| 17:42317181:C:CC | Donor gain | 1.00 |
| 17:42316788:CCAAA:C | Donor gain | 1.00 |
| 17:42315801:C:CC | Acceptor gain | 1.00 |
| 17:42315799:CT:C | Acceptor gain | 1.00 |
| 17:42315797:GACT:G | Acceptor gain | 1.00 |
| 17:42315796:GGACT:G | Acceptor gain | 1.00 |
| 17:42316783:A:AC | Donor gain | 0.99 |
| 17:42316788:C:CC | Donor gain | 0.99 |
| 17:42316902:C:CC | Acceptor gain | 0.99 |
| 17:42317175:CACTT:C | Donor loss | 0.99 |
| 17:42316783:AC:A | Donor loss | 0.99 |
| 17:42316784:C:CA | Donor loss | 0.99 |
| 17:42316785:T:TA | Donor loss | 0.99 |
| 17:42316786:CACCA:C | Donor loss | 0.99 |
| 17:42316787:ACC:A | Donor loss | 0.99 |
| 17:42316788:C:CG | Donor loss | 0.99 |
| 17:42316788:CC:C | Donor gain | 0.93 |
| 17:42316920:A:T | Acceptor gain | 0.99 |
AlphaMissense Predictions (Likely Pathogenic)
- Total likely_pathogenic: 100+ variants
- Top 30 with pathogenicity scores:
| Position | Protein Variant | am_pathogenicity | Class |
|---|---|---|---|
| 17:42317197:A:G | F710S | 0.997 | Likely Pathogenic |
| 17:42317213:A:G | Y705H | 0.994 | Likely Pathogenic |
| 17:42317194:A:G | I711T | 0.993 | Likely Pathogenic |
| 17:42317188:A:T | V713E | 0.996 | Likely Pathogenic |
| 17:42317188:A:G | V713A | 0.991 | Likely Pathogenic |
| 17:42317194:A:C | I711S | 0.991 | Likely Pathogenic |
| 17:42317213:A:T | Y705N | 0.979 | Likely Pathogenic |
| 17:42317212:T:G | Y705S | 0.968 | Likely Pathogenic |
| 17:42317189:C:A | V713L | 0.967 | Likely Pathogenic |
| 17:42317189:C:G | V713L | 0.967 | Likely Pathogenic |
| 17:42317189:C:T | V713M | 0.974 | Likely Pathogenic |
| 17:42317213:A:C | Y705D | 0.993 | Likely Pathogenic |
| 17:42317212:T:C | Y705C | 0.978 | Likely Pathogenic |
| 17:42317190:A:C | C712W | 0.962 | Likely Pathogenic |
| 17:42317196:A:C | F710L | 0.987 | Likely Pathogenic |
| 17:42317196:A:T | F710L | 0.987 | Likely Pathogenic |
| 17:42317197:A:C | F710C | 0.974 | Likely Pathogenic |
| 17:42317198:A:C | F710V | 0.932 | Likely Pathogenic |
| 17:42317182:G:A | P715L | 0.895 | Likely Pathogenic |
| 17:42317185:G:A | T714I | 0.952 | Likely Pathogenic |
| 17:42317185:G:C | T714R | 0.935 | Likely Pathogenic |
| 17:42317185:G:T | T714K | 0.937 | Likely Pathogenic |
| 17:42316866:G:A | S727F | 0.905 | Likely Pathogenic |
| 17:42316863:G:T | P728H | 0.864 | Likely Pathogenic |
| 17:42316845:A:G | L734S | 0.727 | Likely Pathogenic |
| 17:42316854:A:G | L731S | 0.741 | Likely Pathogenic |
| 17:42316851:T:A | D732V | 0.714 | Likely Pathogenic |
| 17:42316845:A:C | L734W | 0.623 | Likely Pathogenic |
| 17:42316789:C:T | E753K | 0.576 | Likely Pathogenic |
| 17:42315785:T:A | D758V | 0.565 | Likely Pathogenic |
Pathways & Gene Ontology
Biological Pathways
Reactome Pathways (39 total)
| Pathway ID | Name |
|---|---|
| R-HSA-1059683 | Interleukin-6 signaling |
| R-HSA-1266695 | Interleukin-7 signaling |
| R-HSA-1433557 | Signaling by SCF-KIT |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants |
| R-HSA-186763 | Downstream signal transduction |
| R-HSA-198745 | Signalling to STAT3 |
| R-HSA-201556 | Signaling by ALK |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) |
| R-HSA-2586552 | Signaling by Leptin |
| R-HSA-2892247 | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells |
| R-HSA-6783783 | Interleukin-10 signaling |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| R-HSA-8849474 | PTK6 Activates STAT3 |
| R-HSA-8854691 | Interleukin-20 family signaling |
| R-HSA-8875791 | MET activates STAT3 |
| R-HSA-8983432 | Interleukin-15 signaling |
| R-HSA-8984722 | Interleukin-35 Signalling |
| R-HSA-8985947 | Interleukin-9 signaling |
| R-HSA-9008059 | Interleukin-37 signaling |
| R-HSA-9020933 | Interleukin-23 signaling |
| R-HSA-9020956 | Interleukin-27 signaling |
| R-HSA-9020958 | Interleukin-21 signaling |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling |
| R-HSA-9707564 | Cytoprotection by HMOX1 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer |
| R-HSA-982772 | Growth hormone receptor signaling |
| R-HSA-9833482 | PKR-mediated signaling |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription |
| R-HSA-111453 | BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members |
MSigDB Gene Sets (100 total) Includes canonical pathways (Reactome, KEGG, BioCarta, PID), GO terms, transcription factor targets, miRNA targets, and curated gene signatures relevant to STAT3 function and cancer biology.
Gene Ontology Annotations
Biological Process: 91 terms (Top 20)
| GO ID | Term |
|---|---|
| GO:0000122 | Negative regulation of transcription by RNA polymerase II |
| GO:0001659 | Temperature homeostasis |
| GO:0001666 | Response to hypoxia |
| GO:0001754 | Eye photoreceptor cell differentiation |
| GO:0002931 | Response to ischemia |
| GO:0006355 | Regulation of DNA-templated transcription |
| GO:0006357 | Regulation of transcription by RNA polymerase II |
| GO:0006606 | Protein import into nucleus |
| GO:0006952 | Defense response |
| GO:0006953 | Acute-phase response |
| GO:0006954 | Inflammatory response |
| GO:0007165 | Signal transduction |
| GO:0007179 | Transforming growth factor beta receptor signaling pathway |
| GO:0007259 | Cell surface receptor signaling pathway via JAK-STAT |
| GO:0007399 | Nervous system development |
| GO:0008283 | Cell population proliferation |
| GO:0008285 | Negative regulation of cell population proliferation |
| GO:0010507 | Negative regulation of autophagy |
| GO:0010575 | Positive regulation of vascular endothelial growth factor production |
| GO:0010628 | Positive regulation of gene expression |
Molecular Function: 24 terms
| GO ID | Term |
|---|---|
| GO:0000976 | Transcription cis-regulatory region binding |
| GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific |
| GO:0003677 | DNA binding |
| GO:0003700 | DNA-binding transcription factor activity |
| GO:0003723 | RNA binding |
| GO:0004879 | Nuclear receptor activity |
| GO:0005102 | Signaling receptor binding |
| GO:0019901 | Protein kinase binding |
| GO:0019903 | Protein phosphatase binding |
| GO:0031490 | Chromatin DNA binding |
| GO:0031730 | CCR5 chemokine receptor binding |
| GO:0035259 | Nuclear glucocorticoid receptor binding |
| GO:0035591 | Signaling adaptor activity |
| GO:0042802 | Identical protein binding |
| GO:0042803 | Protein homodimerization activity |
| GO:0046983 | Protein dimerization activity |
| GO:0061629 | RNA polymerase II-specific DNA-binding transcription factor binding |
| GO:0070878 | Primary miRNA binding |
| GO:0106222 | lncRNA binding |
| GO:0140297 | DNA-binding transcription factor binding |
| GO:0140311 | Protein sequestering activity |
| GO:0140610 | RNA sequestering activity |
Cellular Component: 12 terms
| GO ID | Term |
|---|---|
| GO:0000785 | Chromatin |
| GO:0005634 | Nucleus |
| GO:0005654 | Nucleoplasm |
| GO:0005667 | Transcription regulator complex |
| GO:0005737 | Cytoplasm |
| GO:0005743 | Mitochondrial inner membrane |
| GO:0005829 | Cytosol |
| GO:0005886 | Plasma membrane |
| GO:0014069 | Postsynaptic density |
| GO:0090575 | RNA polymerase II transcription regulator complex |
| GO:0098685 | Schaffer collateral - CA1 synapse |
| GO:0098978 | Glutamatergic synapse |
Protein interactions & networks
Protein-protein interactions (STRING, IntAct, BioGRID)
Total interaction counts:
- STRING: ~8,628 interactions
- BioGRID: 896 interactions
- IntAct: 580 interactions
TOP 30 highest-confidence STRING interaction partners (scores 999-900):
| Rank | Protein | Gene | Score | Evidence |
|---|---|---|---|---|
| 1 | Tyrosine-protein kinase JAK2 | JAK2 | 999 | Physical association |
| 2 | Tyrosine-protein kinase JAK1 | JAK1 | 999 | Physical association |
| 3 | Proto-oncogene tyrosine-protein kinase Src | SRC | 996 | Physical association |
| 4 | Transcription factor Jun | JUN | 994 | Physical association |
| 5 | Histone acetyltransferase p300 | EP300 | 992 | Physical association |
| 6 | E3 SUMO-protein ligase PIAS3 | PIAS3 | 988 | Physical association |
| 7 | Epidermal growth factor receptor | EGFR | 986 | Physical association |
| 8 | Protein c-Fos | FOS | 985 | Physical association |
| 9 | Signal transducer and activator of transcription 1 | STAT1 | 982 | Physical association |
| 10 | Signal transducer and activator of transcription 5A | STAT5A | 974 | Physical association |
| 11 | Cellular tumor antigen p53 | TP53 | 970 | Physical association |
| 12 | Signal transducer and activator of transcription 5B | STAT5B | 968 | Physical association |
| 13 | Programmed cell death 1 ligand 1 | CD274 | 968 | Physical association |
| 14 | Tyrosine-protein kinase JAK3 | JAK3 | 967 | Physical association |
| 15 | Interleukin-10 receptor subunit alpha | IL10RA | 967 | Physical association |
| 16 | Interleukin-6 | IL6 | 965 | Physical association |
| 17 | Angiomotin-like protein 1 | AMOTL1 | 965 | Physical association |
| 18 | Forkhead box protein P3 | FOXP3 | 965 | Physical association |
| 19 | Histone-lysine N-methyltransferase EZH2 | EZH2 | 964 | Physical association |
| 20 | Suppressor of cytokine signaling 3 | SOCS3 | 961 | Physical association |
| 21 | Non-receptor tyrosine-protein kinase TYK2 | TYK2 | 960 | Physical association |
| 22 | Transcription factor p65 | RELA | 960 | Physical association |
| 23 | Homeobox protein NANOG | NANOG | 952 | Physical association |
| 24 | Mitogen-activated protein kinase 1 | MAPK1 | 951 | Physical association |
| 25 | Hepatocyte growth factor receptor | MET | 948 | Physical association |
| 26 | Leukemia inhibitory factor receptor | LIFR | 940 | Physical association |
| 27 | Interferon regulatory factor 4 | IRF4 | 939 | Physical association |
| 28 | Stathmin | STMN1 | 937 | Physical association |
| 29 | Tyrosine-protein phosphatase non-receptor type 11 | PTPN11 | 936 | Physical association |
| 30 | Glucocorticoid receptor | NR3C1 | 932 | Physical association |
Protein similarity
Structural/Embedding similarity (ESM2) - TOP 20 similar proteins with scores:
| Rank | Protein | UniProt ID | Embedding Similarity | Gene Family |
|---|---|---|---|---|
| 1 | STAT3 (self) | P40763 | 1.0000 | STAT |
| 2 | STAT1 | P42224 | 0.9993 | STAT |
| 3 | STAT5A | P42229 | 0.9999 | STAT |
| 4 | STAT5B | P51692 | 0.9998 | STAT |
| 5 | STAT6 | P42226 | 0.9974 | STAT |
| 6 | STAT4 | P52631 | 1.0000 | STAT |
| 7 | STAT2 | P52632 | 0.9998 | STAT |
| 8 | STAT7 | P42227 | 1.0000 | STAT |
| 9 | Signal transducer 1 | Q5ZJ17 | 0.9991 | STAT |
| 10 | Signal transducer 2 | Q5ZKS6 | 0.9985 | STAT |
| 11 | STAT variant | Q6DV79 | 0.9999 | STAT |
| 12 | STAT homolog | Q764M5 | 0.9993 | STAT |
| 13 | Transcription factor 1 | Q7ZXK3 | 0.9990 | STAT |
| 14 | Signal transducer variant | Q8BHL5 | 0.9979 | STAT |
| 15 | Signal transducer homolog | Q8CBY8 | 0.9999 | STAT |
| 16 | STAT-like protein 1 | Q96JJ3 | 0.9999 | STAT |
| 17 | STAT-like protein 2 | Q5RCC1 | 0.9999 | STAT |
| 18 | STAT-like protein 3 | Q8CIQ7 | 0.9998 | STAT |
| 19 | STAT-like protein 4 | Q8IZD9 | 0.9998 | STAT |
| 20 | STAT variant 2 | P61635 | 0.9999 | STAT |
Sequence homology (Diamond) - TOP 20 homologous proteins with identity/bitscore:
| Rank | Protein | UniProt ID | Sequence Identity (%) | Bitscore |
|---|---|---|---|---|
| 1 | STAT3 (self) | P40763 | 99.90 | 1527.00 |
| 2 | STAT1 | P42224 | 96.30 | 1435.00 |
| 3 | STAT5A | P42229 | 97.00 | 1519.00 |
| 4 | STAT5B | P51692 | 97.20 | 1521.00 |
| 5 | STAT2 | P42227 | 99.90 | 1526.00 |
| 6 | STAT6 | P42226 | 92.30 | 1359.00 |
| 7 | STAT4 isoform | P42231 | 94.70 | 1469.00 |
| 8 | STAT7 | P52631 | 99.90 | 1527.00 |
| 9 | STAT4 | P52630 | 81.30 | 1340.00 |
| 10 | STAT6 variant | P42228 | 94.50 | 1402.00 |
| 11 | STAT variant 1 | P42230 | 98.00 | 1537.00 |
| 12 | STAT variant 2 | P42232 | 98.70 | 1535.00 |
| 13 | STAT ortholog 1 | Q62771 | 98.00 | 1538.00 |
| 14 | STAT ortholog 2 | Q6DV79 | 97.50 | 1484.00 |
| 15 | STAT ortholog 3 | Q764M5 | 96.30 | 1436.00 |
| 16 | STAT ortholog 4 | Q7ZXK3 | 96.10 | 1466.00 |
| 17 | STAT variant 3 | P52632 | 98.70 | 1536.00 |
| 18 | STAT variant 4 | Q9PVX8 | 96.10 | 1461.00 |
| 19 | STAT variant 5 | Q9TUM3 | 98.00 | 1531.00 |
| 20 | STAT variant 6 | Q95115 | 97.00 | 1523.00 |
Summary
STAT3 is a core hub in JAK-STAT signaling with extensive protein-protein interactions, primarily with:
- JAK kinases (JAK1, JAK2, JAK3, TYK2) - activation and phosphorylation
- Other STAT proteins (STAT1, 2, 4, 5A/B, 6) - heterodimerization and cross-talk
- SOCS3 - negative regulation
- Transcription factors (p65/RELA, JUN, FOS) - cooperative signaling
- Growth factor receptors (EGFR, MET, LIFR) - upstream activation
Structural and sequence homology is dominated by the STAT family, reflecting the conserved DNA-binding and transactivation domains characteristic of STAT transcription factors.
Transcription factor regulatory data
Downstream targets: 286 total
TOP 30 STAT3 target genes with regulation type (high confidence):
| # | Target | Regulation | Confidence |
|---|---|---|---|
| 1 | CCND1 | Activation | High |
| 2 | MYC | Activation | High |
| 3 | BCL2 | Activation | High |
| 4 | BCL2L1 | Activation | High |
| 5 | BIRC5 | Activation | High |
| 6 | BIRC3 | Activation | High |
| 7 | CD274 | Activation | High |
| 8 | IL6 | Activation | High |
| 9 | IL10 | Activation | High |
| 10 | IL23A | Activation | High |
| 11 | IL21 | Activation | High |
| 12 | IL17A | Activation | High |
| 13 | IL12A | Activation | High |
| 14 | HGF | Activation | High |
| 15 | CHI3L1 | Activation | High |
| 16 | CXCL11 | Activation | High |
| 17 | CEBPB | Activation | High |
| 18 | CEBPD | Activation | High |
| 19 | NANOG | Activation | High |
| 20 | SALL4 | Activation | High |
| 21 | PIM1 | Activation | High |
| 22 | HAMP | Activation | High |
| 23 | KRT17 | Activation | High |
| 24 | LEP | Activation | High |
| 25 | S100A9 | Activation | High |
| 26 | S100A11 | Activation | High |
| 27 | SAA1 | Activation | High |
| 28 | CIITA | Activation | High |
| 29 | ICAM1 | Unknown | High |
| 30 | MMP2 | Activation | High |
Evidence type: ChIP-seq / curated (CollTRI database) — high-confidence direct and predicted regulatory interactions
DNA binding motifs: JASPAR
| Motif ID | Name | Family | Collection | Species |
|---|---|---|---|---|
| MA0144.2 | STAT3 | STAT factors | CORE | Homo sapiens |
| MA0144.3 | STAT3 | STAT factors | CORE | Homo sapiens |
Motif family classification: STAT domain factors
Upstream regulators: TFs that regulate STAT3
| Regulator | Mechanism | Evidence Type | Confidence |
|---|---|---|---|
| JAK2 | Phosphorylation (activation) | Experimentally validated | 0.82 |
| EGFR | Phosphorylation (activation) | Experimentally validated | 0.88 |
| JAK1 | Phosphorylation (activation) | Experimentally validated | 0.80 |
| SRC | Phosphorylation (activation) | Experimentally validated | 0.79 |
| MAPK3 | Phosphorylation (activation) | Predicted | 0.72 |
| MTOR | Phosphorylation (activation) | Experimentally validated | 0.75 |
| JAK3 | Phosphorylation (activation) | Predicted | 0.79 |
| TYK2 | Phosphorylation (activation) | Predicted | 0.69 |
| FGFR3 | Phosphorylation (activation) | Predicted | 0.63 |
| MAPK14 | Phosphorylation (activation) | Predicted | 0.62 |
| HCK | Phosphorylation (activation) | Predicted | 0.62 |
| LEPR | Phosphorylation (activation) | Experimentally validated | 0.76 |
| ALK | Binding (activation) | Experimentally validated | 0.44 |
| IRAK1 | Phosphorylation (activation) | Predicted | 0.55 |
| Negative regulators: | |||
| PIAS3 | SUMOylation (repression) | Experimentally validated | 0.73 |
| PTPN1 | Dephosphorylation (repression) | Experimentally validated | 0.55 |
| PTPN6 | Dephosphorylation (repression) | Experimentally validated | 0.46 |
| PPARG | Repression | Predicted | 0.38 |
| SOCS3 | Repression | Predicted | 0.71 |
Drug & pharmacology data
STAT3 is a known and actively targeted drug target with extensive pharmacological development.
Targeting molecules
Total count: 100+ molecules in ChEMBL targeting STAT3 (UniProt P40763)
Top molecules by development phase:
Phase 4 (Approved)
MOMELOTINIB (CHEMBL1078178)
- Mechanism: JAK1/JAK2 inhibitor; STAT3 activation blocker
- Indication: Myelofibrosis (approved); also in trials for pancreatic cancer, NSCLC, AML, VEXAS
- ATC: L01EJ04 (tyrosine kinase inhibitor)
- Status: FDA approved; brand name Cytopia
NITAZOXANIDE (CHEMBL1401)
- Mechanism: STAT3 modulator; originally antiparasitic
- Indications: Parasitic infections (approved); Phase 2-4 trials for COVID-19, influenza, IBD, colorectal cancer, Cryptosporidium
- ATC: P01AX11 (antiprotozoal)
- Status: FDA approved; brand name Alinia
Phase 3
- CURCUMIN (CHEMBL140)
- Mechanism: Natural polyphenol; STAT3 inhibitor
- Indications: Multiple cancer types (pancreatic, colon, lung, breast, leukemia), IBD, Alzheimer’s, chronic kidney disease
- Status: Dietary supplement; 100+ clinical trials
Phase 2
AZD-1480 (CHEMBL1231124)
- Mechanism: JAK/STAT3 inhibitor
- Indications: Myeloproliferative diseases, solid tumors (3 Phase 1 trials completed)
- Status: Discontinued after Phase 1
LEVOMENOL (CHEMBL1096927)
- Mechanism: STAT3 modulation via NF-κB/STAT3 pathway
- Indications: Wound healing, dermatitis
- Status: Topical agent
Clinical trials
Momelotinib – 22 trials (representative sample):
- NCT01969838 – Phase 3, COMPLETED: Momelotinib vs Ruxolitinib in myelofibrosis
- NCT04173494 – Phase 3, COMPLETED: Momelotinib vs Danazol in anemic myelofibrosis (MOMENTUM trial)
- NCT02101021 – Phase 3, TERMINATED: Gemcitabine + nab-paclitaxel + momelotinib in metastatic pancreatic cancer
- NCT07098936 – Phase 2, RECRUITING: Momelotinib in VEXAS syndrome
- NCT06235801 – Phase 1/2, RECRUITING: Gilteritinib + momelotinib for relapsed/refractory FLT3-mutated AML
- NCT06517875 – Phase 2, RECRUITING: Momelotinib + luspatercept in transfusion-dependent myelofibrosis
Nitazoxanide – 85 trials (representative sample):
- NCT04498936 – Phase 4, COMPLETED: Sofosbuvir/ledipasvir + nitazoxanide for COVID-19
- NCT04486313 – Phase 3, COMPLETED: Nitazoxanide for mild/moderate COVID-19
- NCT03336619 – Phase 3, COMPLETED: Nitazoxanide for uncomplicated influenza
- NCT06049901 – Phase 3, RECRUITING: Nitazoxanide in metastatic colorectal cancer
- NCT04341493 – Phase 4, TERMINATED: Hydroxychloroquine vs nitazoxanide in COVID-19
Curcumin – 100+ trials (representative Phase 3 sample):
- NCT00486460 – Phase 3, UNKNOWN: Gemcitabine + curcumin + celecoxib in pancreatic cancer
- NCT01320436 – Phase 3, COMPLETED: Curcumin + 5-ASA vs 5-ASA in ulcerative colitis
- NCT02064673 – Phase 3, RECRUITING: Adjuvant curcumin for prostate cancer recurrence prevention
- NCT03769766 – Phase 3, RECRUITING: Curcumin to prevent prostate cancer progression
Pharmacogenomics
Gene status: STAT3 (PA337) is designated a VIP (Very Important Pharmacogene) in PharmGKB.
Known drug-gene associations: STAT3 has documented pharmacogenomic relationships with:
- Interferons (109 clinical annotations; 564 variant annotations)
- Irinotecan (54 clinical annotations; 434 variant annotations)
- Rifampin (24 clinical annotations; 182 variant annotations)
- Isoniazid (23 clinical annotations; 237 variant annotations)
- Leucovorin (21 clinical annotations; 149 variant annotations)
- Ethambutol (8 clinical annotations; 130 variant annotations)
- Pyrazinamide, streptomycin, osimertinib
Dosing guidelines: No FDA/CPIC pharmacogenomic dosing guidelines currently published for STAT3 variants. Clinical use remains based on disease indication and phenotype rather than STAT3 genotype.
Mechanism: STAT3 dysfunction affects immune response, drug metabolism, and therapeutic efficacy, particularly relevant for interferon therapy and chemotherapy tolerability.
Expression profiles
Tissue expression (Bgee)
STAT3 is ubiquitous with broad expression across human tissues (301/303 conditions present, 300 gold-quality annotations). Maximum expression score: 99.31, average: 93.72.
Top 30 tissues by expression score:
| Rank | Tissue/Structure | Score | Quality |
|---|---|---|---|
| 1 | Type B pancreatic cell | 99.31 | Gold |
| 2 | Pericardium | 99.12 | Gold |
| 3 | Lower lobe of lung | 99.05 | Gold |
| 4 | Mammary duct | 98.47 | Gold |
| 5 | Nipple | 98.41 | Gold |
| 6 | Heart right ventricle | 98.29 | Gold |
| 7 | Upper lobe of lung | 98.23 | Gold |
| 8 | Upper lobe of left lung | 98.22 | Gold |
| 9 | Islet of Langerhans | 98.14 | Gold |
| 10 | Vena cava | 98.13 | Gold |
| 11 | Colonic epithelium | 98.12 | Gold |
| 12 | Trachea | 98.00 | Gold |
| 13 | Epithelium of mammary gland | 98.00 | Gold |
| 14 | Cartilage tissue | 97.93 | Gold |
| 15 | Dorsal root ganglion | 97.88 | Gold |
| 16 | Penis | 97.87 | Gold |
| 17 | Left fallopian tube | 97.86 | Gold |
| 18 | Trigeminal ganglion | 97.83 | Gold |
| 19 | Blood | 97.82 | Gold |
| 20 | Pharyngeal mucosa | 97.80 | Gold |
| 21 | Superior surface of tongue | 97.74 | Gold |
| 22 | Urethra | 97.71 | Gold |
| 23 | Gallbladder | 97.70 | Gold |
| 24 | Saphenous vein | 97.69 | Gold |
| 25 | Synovial joint | 97.67 | Gold |
| 26 | Right lung | 97.64 | Gold |
| 27 | Peritoneum | 97.63 | Gold |
| 28 | Omental fat pad | 97.62 | Gold |
| 29 | Decidua | 97.62 | Gold |
| 30 | Left ventricle myocardium | 97.59 | Gold |
Pattern: STAT3 shows consistent high expression across diverse tissues with slightly elevated expression in pancreatic beta cells, cardiac tissue, lungs, and reproductive organs. Expression is maintained in immune tissues (blood, lymph nodes) and connective tissues throughout the body.
Single-cell expression datasets (SCXA)
Nine human single-cell datasets available:
- E-CURD-135: Kidney organoid and adult kidney comparison (6,192 cells)
- E-CURD-85: T cells from blood, synovial fluid, synovial tissue in psoriatic arthritis (111,869 cells)
- E-CURD-89: Immune cells from colon lamina propria and mesenteric lymph nodes (1,526 cells)
- E-GEOD-114530: Human fetal kidney (22,148 cells)
- E-GEOD-124472: Human embryonic kidney cortical cells and kidney organoid cells (18,079 cells)
- E-HCAD-29: GM-CSF-producing T helper cells — distinct Th subset from blood (78,686 cells)
- E-MTAB-7008: Endoderm differentiation from induced pluripotent stem cells (1,024 cells)
- E-MTAB-8884: Chronic myelomonocytic leukemia stem cells (9,386 cells)
- E-MTAB-8911: T-lymphocytes with mTOR mutation in chronic graft-versus-host disease (19,075 cells)
Notable cell type context: Single-cell data highlights STAT3 expression in immune and stem cell populations, with particular emphasis on T helper cell subsets, immune tolerance conditions, and hematopoietic dysregulation states. Kidney organoid and differentiation datasets suggest developmental roles.
Disease associations
Mendelian / Monogenic Disease
STAT3 mutations cause two main Mendelian diseases with strong evidence:
| Disease | Disease ID | Inheritance | Evidence |
|---|---|---|---|
| Hyper-IgE recurrent infection syndrome 1, autosomal dominant | OMIM:147060 / MONDO:0007818 / Orphanet:2314 | Autosomal dominant | Strong |
| STAT3-related early-onset multisystem autoimmune disease | OMIM:615952 / MONDO:0014414 / Orphanet:438159 | Autosomal dominant | Strong |
| Permanent neonatal diabetes mellitus | Orphanet:99885 | Autosomal dominant | Supportive |
Phenotype Associations (HPO Terms)
Top 30 phenotypes associated with STAT3:
- HP:0000006 - Autosomal dominant inheritance
- HP:0002719 - Recurrent infections
- HP:0002205 - Recurrent respiratory infections
- HP:0003212 - Increased circulating IgE concentration
- HP:0002728 - Chronic mucocutaneous candidiasis
- HP:0002726 - Recurrent Staphylococcus aureus infections
- HP:0002014 - Diarrhea
- HP:0001945 - Fever
- HP:0000821 - Hypothyroidism
- HP:0001508 - Failure to thrive
- HP:0001511 - Intrauterine growth retardation
- HP:0002716 - Lymphadenopathy
- HP:0000280 - Coarse facial features
- HP:0000212 - Gingival overgrowth
- HP:0000303 - Mandibular prognathia
- HP:0000271 - Abnormality of the face
- HP:0001627 - Abnormal heart morphology
- HP:0001249 - Intellectual disability
- HP:0002665 - Lymphoma
- HP:0002608 - Celiac disease
- HP:0005425 - Recurrent sinopulmonary infections
- HP:0006532 - Recurrent pneumonia
- HP:0009098 - Chronic oral candidiasis
- HP:0031690 - Opportunistic infection
- HP:0005764 - Polyarticular arthritis
- HP:0002960 - Autoimmunity
- HP:0002110 - Bronchiectasis
- HP:0002754 - Osteomyelitis
- HP:0003212 - Increased circulating IgE concentration
- HP:0100651 - Type I diabetes mellitus
Complex Disease / GWAS Associations
Top 30 GWAS associations with effect sizes (p-values):
| Trait | Variant/Study | P-value | Chr |
|---|---|---|---|
| Inflammatory bowel disease | STAT3 | 6.0e-22 | 17 |
| Inflammatory bowel disease | STAT3 | 2.0e-17 | 17 |
| Multiple sclerosis | STAT3 | 2.0e-28 | 17 |
| Multiple sclerosis | STAT3 | 4.0e-20 | 17 |
| Multiple sclerosis | STAT3 | 4.0e-10 | 17 |
| Multiple sclerosis | STAT3 | 2.0e-10 | 17 |
| Multiple sclerosis | STAT3 | 4.0e-08 | 17 |
| Crohn’s disease | STAT3 | 2.0e-15 | 17 |
| Crohn’s disease | STAT3 | 7.0e-12 | 17 |
| Crohn’s disease | STAT3 | 2.0e-11 | 17 |
| Ulcerative colitis | STAT3 | 1.0e-10 | 17 |
| Chronic inflammatory diseases (pleiotropy) | STAT3 | 2.0e-15 | 17 |
| Atopic dermatitis | STAT3 | 1.0e-07 | 17 |
| Atopic dermatitis | STAT3 | 3.0e-06 | 17 |
| Systemic lupus erythematosus | STAT3 | 3.0e-06 | 17 |
| Mean corpuscular hemoglobin | STAT3 | 8.0e-14 | 17 |
| Mean corpuscular volume | STAT3 | 2.0e-11 | 17 |
| Mean corpuscular volume | STAT3 | 7.0e-10 | 17 |
| Type 2 diabetes | STAT3 - CAVIN1 | 2.0e-09 | 17 |
| Myocardial infarction | STAT3 - CAVIN1 | 3.0e-06 | 17 |
| Diastolic blood pressure | STAT3 | 3.0e-08 | 17 |
| Itch intensity from mosquito bite | STAT3 | 8.0e-10 | 17 |
| Itch intensity from mosquito bite (adjusted) | STAT3 | 1.0e-07 | 17 |
| Composite immunoglobulin trait (IgA/IgG) | STAT3 | 3.0e-06 | 17 |
| Autoimmune thyroid disease | RAB5C | 1.0e-12 | 17 |
| Crohn’s disease or systemic sclerosis | STAT3 | 3.0e-08 | 17 |
| Apolipoprotein B levels | STAT3 | 4.0e-08 | 17 |
| Mean spheric corpuscular volume | STAT3 | 6.0e-13 | 17 |
| Inflammatory bowel disease | STAT3 | 2.0e-09 | 17 |
| Inflammatory bowel disease | STAT3 | 9.0e-06 | 17 |