STAT4
Basic information
Region (hg38): 2:191029576-191178435
Links
Phenotypes
GenCC
Source:
- disabling pansclerotic morphea of childhood (Limited), mode of inheritance: AD
- systemic lupus erythematosus (Supportive), mode of inheritance: Unknown
Clinical Genomic Database
Source:
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
- not_provided (407 variants)
- not_specified (42 variants)
- STAT4-related_disorder (10 variants)
- Disabling_pansclerotic_morphea_of_childhood (4 variants)
- Systemic_lupus_erythematosus,_susceptibility_to,_11 (1 variants)
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. These statistics are base on transcript: NM_000003151.4. Only rare variants are included in the table.
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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 98 | 106 | ||||
missense | 173 | 11 | 188 | |||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 1 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
Total | 2 | 1 | 182 | 109 | 5 |
GnomAD
Source:
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:
- 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