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STAT3

signal transducer and activator of transcription 3

The STAT3 gene provides instructions for a protein crucial in cellular signalling pathways, influencing cell growth, division, and immune system function. The STAT3 gene is a key component of the STAT gene family, which encodes proteins involved in essential cellular signalling.

Chromosome 17q21.2 Autosomal dominant HGNC:11364 Tier C
STAT3 17q21.2 p arm q arm 17

STAT3 is located on the long (q) arm of chromosome 17, at band 17q21.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 17 in the library →

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Clinical tests that include this

KNOVA NIPT
STAT3 is 1 of 56 genes on this panel
Prenatal NIPT screening (trisomies, microdeletions, single-gene conditions)

Overview

The STAT3 gene, or signal transducer and activator of transcription 3, is a vital gene in the human genome. It produces a protein that plays a central role in numerous cellular processes, including cell proliferation, migration, and programmed cell death. Dysregulation of STAT3 function can have significant implications for health, particularly concerning the immune system and cellular development.

What the gene does

The STAT3 protein functions as a transcription factor, meaning it helps to control whether specific genes are switched on or off. When activated by various chemical signals, STAT3 moves into the cell's nucleus and binds to particular DNA regions. This binding action regulates gene expression, thereby influencing a wide array of cellular functions.

Its involvement is critical for the maturation of immune cells, such as T cells and B cells, which are essential for the body's defence against infections. Furthermore, STAT3 contributes to the regulation of inflammation and cellular processes involved in allergic reactions. In the skeletal system, it is important for the formation of cells that build and break down bone tissue, ensuring proper bone development and maintenance.

Video: Genetics 101

Chromosome location

The STAT3 gene is situated on chromosome 17 at position 17q21.2. This specific genomic location places it within a region that is frequently studied for its association with various genetic conditions.

Protein structure

The STAT3 protein comprises 770 amino acids and includes several important functional regions. An essential Motif, located between amino acids 150-162, is critical for the protein's transport into the cell nucleus. Additionally, an SH2 Domain, spanning amino acids 580-670, is vital for protein-protein interactions and the binding of phosphotyrosine residues, which is key for its activation and signalling capabilities.

Domain map · 770 amino acids
Essential for nuclear import (150–162)SH2 (580–670)Essential for nuclear 150–162SH2580–6701~385770
Motif - short conserved sequence
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:P40763Length:770 aaStructure:AlphaFold

Key variants

Genetic variations within the STAT3 gene can alter the function of the STAT3 protein, leading to a range of health conditions. These variants can either reduce (loss-of-function) or enhance (gain-of-function) the protein's activity. The specific effect of a variant often dictates the clinical presentation of an associated condition.

912
Total variants catalogued in ClinVar
View all on ClinVar →
101 Pathogenic / Likely pathogenic 332 Uncertain significance 440 Benign / Likely benign 39 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1003C>T
single nucleotide variant
 p.Arg335Trp Pathogenic/Likely pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1144C>T
single nucleotide variant
 p.Arg382Trp Pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1145G>A
single nucleotide variant
 p.Arg382Gln Pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1243G>A
single nucleotide variant
 p.Glu415Lys Pathogenic/Likely pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1261G>A
single nucleotide variant
 p.Gly421Arg Pathogenic/Likely pathogenic ★★☆☆ STAT3-related early-onset multisystem autoimmune disease
c.1268G>A
single nucleotide variant
 p.Arg423Gln Pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1384GTG[1]
Microsatellite
 p.Val463del Pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1397A>C
single nucleotide variant
 p.Asn466Thr Pathogenic/Likely pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1397A>G
single nucleotide variant
 p.Asn466Ser Pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant
c.1863C>A
single nucleotide variant
 p.Phe621Leu Pathogenic/Likely pathogenic ★★☆☆ Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Mutations in the STAT3 gene are associated with several inherited conditions. These include Autosomal Dominant Hyper-IgE Syndrome (AD-HIES), an immune disorder characterised by recurrent infections and skeletal abnormalities. Additionally, specific variants can lead to STAT3 gain-of-function disease, which presents with different clinical features.

Inheritance pattern

Conditions caused by pathogenic STAT3 variants typically follow autosomal dominant inheritance.

♀ Affected parent 1 altered copy ♂ Unaffected parent 2 typical copies Affected Unaffected Unaffected Affected Affected Carrier Unaffected Circles = females · Squares = males

Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.

UK clinical status

In the UK, the STAT3 gene is recognised on several NHS Genomic Medicine Service national test panels, indicating its clinical significance. It is listed on panels for conditions such as COVID-19 research, Diabetes with additional phenotypes, Familial diabetes, and Primary immunodeficiency or monogenic inflammatory bowel disease, among others. Its inclusion on these panels highlights its established role in diagnosing and understanding a variety of health issues.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Neonatal diabetes · R143 NHS GMS → Primary immunodeficiency or monogenic inflammatory bowel disease · R15 NHS GMS → Rare genetic inflammatory skin disorders · R332 NHS GMS → Rare syndromic craniosynostosis or isolated multisuture synostosis · R100 NHS GMS → Haematological malignancies cancer susceptibility NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What does the STAT3 gene do?

The STAT3 gene produces a protein that acts as a transcription factor, controlling the activation or deactivation of other genes. This function is critical for cell growth, division, migration, and particularly for the development and function of the immune system.

What is Autosomal Dominant Hyper-IgE Syndrome?

Autosomal Dominant Hyper-IgE Syndrome (AD-HIES) is an inherited immune disorder caused by mutations in the STAT3 gene. It typically leads to recurrent skin and lung infections, as well as characteristic abnormalities affecting bones, teeth, and blood vessels.

How does the STAT3 protein regulate gene activity?

When activated by specific chemical signals, the STAT3 protein translocates into the cell's nucleus. There, it binds directly to particular regions of DNA, which allows it to either promote or inhibit the expression of nearby genes, thereby regulating various cellular processes.

References

  1. Hox V, O'Connell MP, Lyons JJ. Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. The Journal of allergy and clinical immunology. 2016. PMID: 26948077
  2. Haapaniemi EM, Kaustio M, Rajala HL. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3. Blood. 2015. PMID: 25349174
  3. Milner JD, Vogel TP, Forbes L. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood. 2015. PMID: 25359994
  4. Kane A, Deenick EK, Ma CS. STAT3 is a central regulator of lymphocyte differentiation and function. Current opinion in immunology. 2014. PMID: 24594518
  5. Siegel AM, Stone KD, Cruse G. Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation. The Journal of allergy and clinical immunology. 2013. PMID: 24184145
  6. Jerez A, Clemente MJ, Makishima H. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood. 2012. PMID: 22859607
  7. Frank DA. STAT3 as a central mediator of neoplastic cellular transformation. Cancer letters. 2007. PMID: 17129668
  8. Gao H, Ward PA. STAT3 and suppressor of cytokine signaling 3: potential targets in lung inflammatory responses. Expert opinion on therapeutic targets. 2007. PMID: 17614756
  9. Minegishi Y, Saito M, Tsuchiya S. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007. PMID: 17676033
  10. Holland SM, DeLeo FR, Elloumi HZ. STAT3 mutations in the hyper-IgE syndrome. The New England journal of medicine. 2007. PMID: 17881745
  11. Levy DE, Loomis CA. STAT3 signaling and the hyper-IgE syndrome. The New England journal of medicine. 2007. PMID: 17881746
  12. Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. European journal of cancer (Oxford, England : 1990). 2005. PMID: 16199153
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .