STAT4

signal transducer and activator of transcription 4, the group of SH2 domain containing

Basic information

Region (hg38): 2:191029576-191178435

Links

ENSG00000138378 ∙ NCBI:6775 ∙ OMIM:600558 ∙ HGNC:11365 ∙ Uniprot:Q14765 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• disabling pansclerotic morphea of childhood (Limited), mode of inheritance: AD
• systemic lupus erythematosus (Supportive), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Disabling pansclerotic morphea of childhood	AD	Allergy/Immunology/Infectious; Oncologic	The condition involves multisystem sequelae, including cytopenias, fibrosis, hypogammaglobulinemi, poor wound healing, and squamous-cell carcinoma, and surveillance for complications as well as medical management (eg, with the JAK inhibitor ruxolitinib) has been reported as beneficial	Allergy/Immunology/Infectious; Dermatologic; Oncologic	37256972

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAT4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAT4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	89	4	97
missense			138	5	1	144
nonsense						0
start loss						0
frameshift			1			1
inframe indel			2			2
splice donor/acceptor (+/-2bp)			2			2
splice region			9	19	8	36
non coding			3	80	7	90
Total	0	0	150	174	12

Variants in STAT4

This is a list of pathogenic ClinVar variants found in the STAT4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-191029849-A-G			Likely benign (Oct 26, 2022)
2-191030962-G-A			Likely benign (Nov 21, 2024)
2-191030973-G-A			Uncertain significance (Mar 08, 2021)
2-191030975-A-C			Likely benign (Aug 11, 2021)
2-191030975-A-G			Likely benign (Dec 18, 2021)
2-191030979-T-G			Uncertain significance (Jul 19, 2022)
2-191030982-ATTG-A			Uncertain significance (Oct 24, 2022)
2-191030984-T-A			Likely benign (Oct 29, 2024)
2-191030985-G-T			Uncertain significance (Nov 28, 2023)
2-191030989-T-C		not specified	Uncertain significance (May 11, 2023)
2-191031014-C-T			Likely benign (Jan 08, 2025)
2-191031018-T-C			Uncertain significance (Sep 06, 2024)
2-191031020-C-A			Likely benign (Jan 22, 2023)
2-191031041-A-C			Likely benign (Aug 02, 2024)
2-191031065-T-C			Likely benign (Feb 24, 2024)
2-191031067-T-C			Uncertain significance (Oct 01, 2024)
2-191031078-C-T			Uncertain significance (Dec 08, 2024)
2-191031079-G-A			Uncertain significance (Sep 08, 2024)
2-191031093-A-G			Uncertain significance (Nov 03, 2024)
2-191031094-C-T			Likely benign (Feb 22, 2022)
2-191031096-A-C			Likely benign (Jun 02, 2023)
2-191031097-G-C			Likely benign (Mar 17, 2023)
2-191031432-G-A			Likely benign (Aug 07, 2024)
2-191031440-C-T			Likely benign (Jan 08, 2024)
2-191031451-T-C		not specified	Uncertain significance (Jun 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAT4	protein_coding	protein_coding	ENST00000392320	23	122021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.766	0.234	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.74	237	389	0.609	0.0000191	4951
Missense in Polyphen		56	136.98	0.40882		1771
Synonymous	1.25	120	139	0.864	0.00000736	1347
Loss of Function	5.15	10	48.8	0.205	0.00000239	577

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000713	0.0000703
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000701	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:17804842, ECO:0000269|PubMed:19109131}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:17804842}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;JAK-STAT-Core;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;no2-dependent il-12 pathway in nk cells;Interferon type I signaling pathways;Interleukin-12 family signaling;Signaling by Interleukins;il12 and stat4 dependent signaling pathway in th1 development;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;IL-12 signaling;IL12 signaling mediated by STAT4;Immune System;IL-23 signaling;Interleukin-23 signaling;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;IL2;Interleukin-12 signaling;IL23-mediated signaling events;IL27-mediated signaling events;Downstream signaling in naïve CD8+ T cells;IL12-mediated signaling events;TSLP (Consensus)

Recessive Scores

• pRec: 0.262

Intolerance Scores

• loftool: 0.339
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.897
• hipred: Y
• hipred_score: 0.655
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Stat4
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Gene ontology

• Biological process: JAK-STAT cascade;cytokine-mediated signaling pathway;interleukin-12-mediated signaling pathway;interleukin-21-mediated signaling pathway;interleukin-23-mediated signaling pathway;positive regulation of transcription by RNA polymerase II;interleukin-35-mediated signaling pathway
• Cellular component: nucleoplasm;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;identical protein binding