STAT1

Chr 2ADAR

signal transducer and activator of transcription 1

Also known as: CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91

NCBI Gene: 6772ENSG00000115415UniProt: P42224

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. The protein encoded by this gene can be activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6. This protein mediates the expression of a variety of genes, which is thought to be important for cell viability in response to different cell stimuli and pathogens. The protein plays an important role in immune responses to viral, fungal and mycobacterial pathogens. Mutations in this gene are associated with Immunodeficiency 31B, 31A, and 31C. [provided by RefSeq, Jun 2020]

Primary Disease Associations & Inheritance

Immunodeficiency 31A, mycobacteriosis, autosomal dominantMIM #614892
AD
Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessiveMIM #613796
AR
Immunodeficiency 31C, chronic mucocutaneous candidiasis, autosomal dominantMIM #614162
AD
555
ClinVar variants
59
Pathogenic / LP
1.00
pLI score· haploinsufficient
5
Active trials
Clinical Summary— STAT1
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency 31B · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

3 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.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 193 VUS of 555 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
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.
0.19LOEUF
pLI 1.000
Z-score 5.95
OE 0.08 (0.04–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
5.15Z-score
OE missense 0.28 (0.24–0.33)
114 obs / 406.0 exp
Constrained

Extremely missense-constrained (top ~0.01%)

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.0.08 (0.04–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.28 (0.24–0.33)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 4 / 48.9Missense obs/exp: 114 / 406.0Syn Z: -0.23

ClinVar Variant Classifications

555 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic22
VUS193
Likely Benign276
Benign27
37
Pathogenic
22
Likely Pathogenic
193
VUS
276
Likely Benign
27
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
12
14
0
37
Likely Pathogenic
5
15
2
0
22
VUS
3
147
36
7
193
Likely Benign
0
4
147
125
276
Benign
0
0
27
0
27
Total19178226132555

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STAT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

STAT1-related immunodeficiency

limited
ARUndeterminedAltered Gene Product Structure
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency 31A, mycobacteriosis, autosomal dominant

MIM #614892

Molecular basis of disorder known

Autosomal dominant

Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive

MIM #613796

Molecular basis of disorder known

Autosomal recessive

Immunodeficiency 31C, chronic mucocutaneous candidiasis, autosomal dominant

MIM #614162

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — STAT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The PRMT6/STAT1/ACSL1 axis promotes ferroptosis in diabetic nephropathy.
Hong J et al.·Cell Death Differ
2024
Single cell immunoprofile of synovial fluid in rheumatoid arthritis with TNF/JAK inhibitor treatment.
Xia X et al.·Nat Commun
2025
JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences.
Ott N et al.·J Clin Immunol
2023Review
STAT1 and STAT3 gain of function: clinically heterogenous immune regulatory disorders.
Olbrich P et al.·Curr Opin Allergy Clin Immunol
2024Review
ID1 expressing macrophages support cancer cell stemness and limit CD8(+) T cell infiltration in colorectal cancer.
Shang S et al.·Nat Commun
2023
Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype.
Toubiana J et al.·Blood
2016
Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer.
Palakurthi B et al.·Nat Commun
2023
TNIP3 protects against pathological cardiac hypertrophy by stabilizing STAT1.
Shi H et al.·Cell Death Dis
2024
Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1.
Zang X et al.·Mol Cancer
2024
Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
López-Nevado M et al.·Front Immunol
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
TGEV activates RIG-I/IFN-β/STAT1 axis to promote NLRC5-mediated SLA-I upregulation.
Wang W et al.·Vet Res
2026
Phenolic Fraction of Elsholtzia penduliflora W.W.Sm. Ameliorates Influenza A virus-Induced Acute Lung Injury by Inhibiting the IDO-1-Mitochondria-STAT1 Signaling Axis.
Liu Y et al.·J Ethnopharmacol
2026
Integration of multi-omics and machine learning to reveal the anti-osteoporosis effects of Hederagenin by inhibiting lipid peroxidation via the GPX4/p-STAT1/PTGS2 axis.
Lu J et al.·Biochem Pharmacol
2026
LncRNA NORAD Enhances Inflammatory Injury in Sepsis-Associated Acute Lung Damage Through miR-150-5p/STAT1-Dependent NF-κB Activation.
Liu H et al.·Kaohsiung J Med Sci
2026
BATF Drives Cervical Cancer Progression and Immune Evasion by Regulating the STAT1-PD-L1 Axis.
Zhang J et al.·Iran J Immunol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Enteric FeverAcute Febrile IllnessTyphoid

Transcriptomic Responses for the Identification of Pathogens

RECRUITING
NCT04878549University of SheffieldStarted 2022-05-02
5-gene transcription signature
Lassa Fever

ISTH/ANRS 0409s INTEGRATE Lassa Fever Study

RECRUITING
NCT06212336Phase PHASE2, PHASE3Irrua Specialist Teaching HospitalStarted 2025-05-02
FavipiravirRibavirinDexamethasone
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
DOK 8STAT1GATA2

Genetic Analysis of Immune Disorders

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

The Role of B7-H4 in Tumor Vaccine

RECRUITING
NCT06156150Huashan HospitalStarted 2023-11-26
tumor vaccine

External Resources

Links to major genomics databases and tools