STAT3

Chr 17AD

signal transducer and activator of transcription 3

Also known as: ADMIO, ADMIO1, APRF, HIES

The protein encoded by this gene is a member of the STAT protein family. 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 activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

Autoimmune disease, multisystem, infantile-onset, 1MIM #615952
AD
Hyper-IgE syndrome 1, autosomal dominant, with recurrent infectionsMIM #147060
AD
8
Active trials
0
ClinVar variants
0
Pathogenic / LP
5.0
Missense Z· constrained
0.10
LOEUF· LoF intolerant
13
Pubs (2 yr)
Clinical SummarySTAT3
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Gene-Disease Validity (ClinGen)
STAT3-related early-onset multisystem autoimmune disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — STAT3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.10LOEUF
pLI 1.000
Z-score 6.43
OE 0.02 (0.010.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.99Z-score
OE missense 0.31 (0.270.36)
131 obs / 418.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.010.10)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.31 (0.270.36)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
01.21.6
LoF obs/exp: 1 / 50.1Missense obs/exp: 131 / 418.5Syn Z: 0.24

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

STAT3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

Autoimmune disease, multisystem, infantile-onset, 1

MIM #615952

Molecular basis of disorder known

Autosomal dominant

Hyper-IgE syndrome 1, autosomal dominant, with recurrent infections

MIM #147060

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Targeting the STAT3 pathway with STAT3 degraders.
Wang Z et al.·Trends Pharmacol Sci
2024
T Stat3
Xu YX et al.·Zhonghua Xue Ye Xue Za Zhi
2025
The Pulmonary Effects of STAT3 Deficiency.
Gilje EA et al.·J Allergy Clin Immunol
2023
STAT3 T
Liu HL et al.·Zhonghua Xue Ye Xue Za Zhi
2021
STAT3 Signaling Pathway in Health and Disease
Samad MA et al.·MedComm (2020)
2025
Perspective: mitochondrial STAT3 in cardioprotection
Kleinbongard P·Basic Res Cardiol
2023
Top 10 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Inflammatory Breast Cancer (IBC)

Study Of Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer

ACTIVE NOT RECRUITING
NCT02876302Phase PHASE2Dana-Farber Cancer InstituteStarted 2018-01-24
RuxolitinibPaclitaxelDoxorubicin
Esophageal AdenocarcinomaOesophageal AdenocarcinomaResectable Carcinoma

Blood-borne Assessment of Stromal Activation in Esophageal Adenocarcinoma to Guide Tocilizumab Therapy

ACTIVE NOT RECRUITING
NCT04554771Phase PHASE2Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Started 2021-01-27
Tocilizumab 20 Mg/mL Intravenous SolutionPaclitaxelCarboplatin
Type1 Diabetes Mellitus

EXtremely Early-onset Type 1 Diabetes EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)

RECRUITING
NCT03369821University of ExeterStarted 2017-09-19
Beta Cell Loss and Immune FunctionImmune Function with RNAseq
Overweight and ObesityLupus Erythematosus

Methyl-donor Nutrient Supplementation and Methylation Profile in Lupus Patients With Obesity

ENROLLING BY INVITATION
NCT05097365Phase NAUniversity of Sao PauloStarted 2022-01-01
Vitamin B12 + folic acid supplementationPlacebo supplementation
Primary Immunodeficiency Diseases (PID)

Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders

RECRUITING
NCT07261891Phase NAprof. dr. Rik SchrijversStarted 2024-11-21
blood sampling
Lung CancerNSCLC

Modulatory Effect of Prodigiosin or Pioglitazone on TIME and the Crosstalk to Immune-Checkpoint Protein(s)

NOT YET RECRUITING
NCT06502249Ain Shams UniversityStarted 2026-06
DOK 8STAT1GATA2

Genetic Analysis of Immune Disorders

RECRUITING
NCT00001467National Institute of Allergy and Infectious Diseases (NIAID)Started 1995-06-06
Psoriatic Arthritis

Rewiring the Brain-Immune Axis for Chronic Pain Using Transcranial Magnetic Stimulation in Psoriatic Arthritis

NOT YET RECRUITING
NCT07403890Phase NANHS Greater Glasgow and ClydeStarted 2026-03-01
Active Repetitive Transcranial Magnetic Stimulation (rTMS)Control Repetitive Transcranial Magnetic Stimulation (rTMS)