STAT6

signal transducer and activator of transcription 6, the group of SH2 domain containing

Basic information

Region (hg38): 12:57095407-57132139

Links

ENSG00000166888 ∙ NCBI:6778 ∙ OMIM:601512 ∙ HGNC:11368 ∙ Uniprot:P42226 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections	AD	Allergy/Immunology/Infectious	The condition can manifest with multisystem immunologic features, incluidng frequent infections, and medical management (eg, with IL4 inhibitors or JAK inhibitors) as well as early and aggressive treatment of infections, may be beneficial; Individuals have been described with anaphylactic allergic reactions, and awareness may allow identification and triggers and avoidance and prompt management of allergic reactions; The condition can involve cerebrovascular anomalies, and early identification may improve outcomes;	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary	36758835; 36884218; 37316763

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAT6 gene.

• Inborn genetic diseases (26 variants)
• not provided (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAT6 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				6	1	7
missense			27	1	2	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	2	3
Total	0	0	27	8	5

Variants in STAT6

This is a list of pathogenic ClinVar variants found in the STAT6 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-57096634-G-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
12-57096708-G-T			Likely benign (Jun 29, 2018)
12-57096945-A-G			Likely benign (Mar 01, 2023)
12-57096947-C-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
12-57097086-A-G		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
12-57097131-G-A		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
12-57098510-G-A			Benign (Jan 05, 2018)
12-57098524-C-T			Benign (Jun 29, 2018)
12-57099333-T-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
12-57099365-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
12-57099366-G-A		Inborn genetic diseases	Uncertain significance (Dec 16, 2022)
12-57099375-C-T		Inborn genetic diseases	Uncertain significance (Nov 24, 2021)
12-57099437-G-C		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
12-57099758-T-G			Likely benign (Aug 17, 2018)
12-57099781-A-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
12-57099793-A-G			Uncertain significance (Dec 13, 2022)
12-57099819-G-A			Benign/Likely benign (Mar 01, 2023)
12-57100014-C-T		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
12-57100048-C-G		Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections	Pathogenic (Jan 31, 2024)
12-57100088-C-A		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
12-57102294-T-C		Inborn genetic diseases	Uncertain significance (Feb 02, 2022)
12-57102300-T-A		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
12-57102405-T-C		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
12-57102490-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
12-57102832-C-T			Likely benign (Apr 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAT6	protein_coding	protein_coding	ENST00000300134	21	36732

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0115	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.41	336	486	0.692	0.0000271	5516
Missense in Polyphen		93	198.98	0.46739		2347
Synonymous	0.204	190	194	0.981	0.0000106	1715
Loss of Function	5.41	8	48.7	0.164	0.00000261	499

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling. {ECO:0000269|PubMed:17210636}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);JAK-STAT-Core;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Adipogenesis;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;PDGFR-beta pathway;Interleukin-4 and 13 signaling;Signal Transduction;Signaling by Interleukins;il 4 signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;STING mediated induction of host immune responses;Signaling by PDGF;STAT6-mediated induction of chemokines;Innate Immune System;Immune System;IL-4 signaling;JAK STAT MolecularVariation 2;Signaling events mediated by TCPTP;JAK STAT pathway and regulation;Downstream signal transduction;IL4;Cytosolic sensors of pathogen-associated DNA ;Signaling by Receptor Tyrosine Kinases;IL9;IL4-mediated signaling events;IL12-mediated signaling events;IL-13 signaling;TSLP (Consensus)

Recessive Scores

• pRec: 0.752

Intolerance Scores

• loftool: 0.0386
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.27

Haploinsufficiency Scores

• pHI: 0.950
• hipred: Y
• hipred_score: 0.595
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stat6
• Phenotype: hematopoietic system phenotype; reproductive 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); neoplasm; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;T-helper 1 cell lineage commitment;negative regulation of type 2 immune response;regulation of transcription by RNA polymerase II;signal transduction;cytokine-mediated signaling pathway;positive regulation of type I interferon production;mammary gland epithelial cell proliferation;interleukin-4-mediated signaling pathway;regulation of cell population proliferation;positive regulation of transcription by RNA polymerase II;positive regulation of isotype switching to IgE isotypes;mammary gland morphogenesis;cellular response to hydrogen peroxide;positive regulation of cold-induced thermogenesis;cellular response to reactive nitrogen species
• Cellular component: nuclear chromatin;nucleoplasm;cytosol;nuclear membrane;membrane raft
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;protein phosphatase binding;identical protein binding