STAT6 signal transducer and activator of transcription 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: STAT6provided by HGNC
Official Full Name: signal transducer and activator of transcription 6provided by HGNC
Primary source: HGNC:HGNC:11368
See related: Ensembl:ENSG00000166888 MIM:601512; AllianceGenome:HGNC:11368
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HIES6; STAT6B; STAT6C; D12S1644; IL-4-STAT
Summary: The protein encoded by this gene is a member of the STAT family of transcription factors. 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. This protein plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
Expression: Ubiquitous expression in spleen (RPKM 48.4), skin (RPKM 47.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (57095408..57111362, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (57063280..57079195, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (57489191..57505145, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases.
Title: STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases.
The aryl hydrocarbon receptor shapes monocyte transcriptional responses to interleukin-4 by prolonging STAT6 binding to promoters.
Title: The aryl hydrocarbon receptor shapes monocyte transcriptional responses to interleukin-4 by prolonging STAT6 binding to promoters.
NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors.
Title: NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors.
Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.
Title: Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.
STAT6 mutations enriched at diffuse large B-cell lymphoma relapse reshape the tumor microenvironment.
Title: STAT6 mutations enriched at diffuse large B-cell lymphoma relapse reshape the tumor microenvironment.
Major vault protein regulates tumor-associated macrophage polarization through interaction with signal transducer and activator of transcription 6.
Title: Major vault protein regulates tumor-associated macrophage polarization through interaction with signal transducer and activator of transcription 6.
Human germline gain-of-function in STAT6: from severe allergic disease to lymphoma and beyond.
Title: Human germline gain-of-function in STAT6: from severe allergic disease to lymphoma and beyond.
STAT6 promoting oxalate crystal deposition-induced renal fibrosis by mediating macrophage-to-myofibroblast transition via inhibiting fatty acid oxidation.
Title: STAT6 promoting oxalate crystal deposition-induced renal fibrosis by mediating macrophage-to-myofibroblast transition via inhibiting fatty acid oxidation.
Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma.
Title: Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma.
Lactobacillus rhamnosus 76 alleviates airway inflammation in ovalbumin-allergic mice and improves mucus secretion by down-regulating STAT6/SPDEF pathway.
Title: Lactobacillus rhamnosus 76 alleviates airway inflammation in ovalbumin-allergic mice and improves mucus secretion by down-regulating STAT6/SPDEF pathway.

Submit: New GeneRIF Correction See all GeneRIFs (296)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections MedGen: C5848786 OMIM: 620532 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 5q22 associate with pediatric eosinophilic esophagitis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of sensory disturbances in the inferior alveolar nerve after bilateral sagittal split ramus osteotomy. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS identifies four novel eosinophilic esophagitis loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Activation of IL-4/STAT6 signaling partially contributes to HIV-1 Tat-induced Kaposi's sarcoma-associated herpes virus (KSHV) replication	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_2391-2392:991932733:1 (e-PCR)
- UniSTS:230919

STAT6_856 (e-PCR)
- UniSTS:277775

STAT6_V164 (e-PCR)
- UniSTS:277775

RH44534 (e-PCR)
- UniSTS:7955

G32703 (e-PCR)
- UniSTS:117285

G54117 (e-PCR)
- UniSTS:109354

STS-X70991 (e-PCR)
- UniSTS:30515

D12S1691 (e-PCR)
- UniSTS:54837

D12S1644 (e-PCR), detects polymorphism
- UniSTS:13907

RH70573 (e-PCR)
- UniSTS:9453

A009O16 (e-PCR)
- UniSTS:77301

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coactivator binding	EXP Inferred from Experiment more info	PubMed

Process	Evidence Code	Pubs
involved_in T-helper 1 cell lineage commitment	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway via JAK-STAT	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to reactive nitrogen species	IEA Inferred from Electronic Annotation more info
involved_in cytokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytokine-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response	IBA Inferred from Biological aspect of Ancestor more info
involved_in growth hormone receptor signaling pathway via JAK-STAT	IBA Inferred from Biological aspect of Ancestor more info
involved_in interleukin-4-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in interleukin-4-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in isotype switching to IgE isotypes	IEA Inferred from Electronic Annotation more info
involved_in mammary gland epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in mammary gland morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of type 2 immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of isotype switching to IgE isotypes	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of mast cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to peptide hormone	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of RNA polymerase II transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info
part_of RNA polymerase II transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed
part_of RNA polymerase II transcription regulator complex	NAS Non-traceable Author Statement more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: signal transducer and activator of transcription 6

Names: STAT, interleukin4-induced; signal transducer and activator of transcription 6, interleukin-4 induced; transcription factor IL-4 STAT

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_021272.2 RefSeqGene

Range

25778..41732

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1369

mRNA and Protein(s)

NM_001178078.2 → NP_001171549.1 signal transducer and activator of transcription 6 isoform 1

See identical proteins and their annotated locations for NP_001171549.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Variants 1, 2 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC023237, AI082533, AK290431

Consensus CDS

CCDS8931.1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4

UniProtKB/TrEMBL

A8K4S9, B2R680

Related

ENSP00000401486.3, ENST00000454075.7

Conserved Domains (5) summary

cd10377
Location:517 → 646

SH2_STAT6; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 proteins

smart00964
Location:2 → 115

STAT_int; STAT protein, protein interaction domain

pfam14596
Location:655 → 847

STAT6_C; STAT6 C-terminal

pfam01017
Location:124 → 271

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:273 → 526

STAT_bind; STAT protein, DNA binding domain
NM_001178079.2 → NP_001171550.1 signal transducer and activator of transcription 6 isoform 1

See identical proteins and their annotated locations for NP_001171550.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC023237, AI082533, AK291044

Consensus CDS

CCDS8931.1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4

UniProtKB/TrEMBL

A8K4S9, B2R680

Related

ENSP00000438451.2, ENST00000543873.6

Conserved Domains (5) summary

cd10377
Location:517 → 646

SH2_STAT6; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 proteins

smart00964
Location:2 → 115

STAT_int; STAT protein, protein interaction domain

pfam14596
Location:655 → 847

STAT6_C; STAT6 C-terminal

pfam01017
Location:124 → 271

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:273 → 526

STAT_bind; STAT protein, DNA binding domain
NM_001178080.2 → NP_001171551.1 signal transducer and activator of transcription 6 isoform 2

See identical proteins and their annotated locations for NP_001171551.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the 5' UTR, lacks an alternate in-frame exon in the 5' coding region and uses a downstream start codon compared to variant 1. The resulting protein (isoform 2 )has a shorter N-terminus compared to isoform 1. Variants 4 and 5 encode the same protein.

Source sequence(s)

AC023237, AK316142

Consensus CDS

CCDS53804.1

UniProtKB/TrEMBL

B7ZAC1

Related

ENSP00000444530.2, ENST00000537215.6

Conserved Domains (4) summary

cd10377
Location:407 → 536

SH2_STAT6; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 proteins

pfam01017
Location:14 → 161

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:163 → 416

STAT_bind; STAT protein, DNA binding domain

pfam14596
Location:545 → 737

STAT6_C; STAT6 C-terminal
NM_001178081.2 → NP_001171552.1 signal transducer and activator of transcription 6 isoform 2

See identical proteins and their annotated locations for NP_001171552.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR, lacks two alternate in-frame exons in the 5' coding region and uses a downstream start codon compared to variant 1. The resulting protein (isoform 2) has a shorter N-terminus compared to isoform 1. Variants 4 and 5 encode the same protein.

Source sequence(s)

AC023237, AI082533, AK298721

Consensus CDS

CCDS53804.1

UniProtKB/TrEMBL

B7ZAC1

Related

ENSP00000445409.2, ENST00000538913.6

Conserved Domains (4) summary

cd10377
Location:407 → 536

SH2_STAT6; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 proteins

pfam01017
Location:14 → 161

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:163 → 416

STAT_bind; STAT protein, DNA binding domain

pfam14596
Location:545 → 737

STAT6_C; STAT6 C-terminal
NM_003153.5 → NP_003144.3 signal transducer and activator of transcription 6 isoform 1

See identical proteins and their annotated locations for NP_003144.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC023237, AI082533, BC005823

Consensus CDS

CCDS8931.1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4

UniProtKB/TrEMBL

A8K4S9, B2R680

Related

ENSP00000300134.3, ENST00000300134.8

Conserved Domains (5) summary

cd10377
Location:517 → 646

SH2_STAT6; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 6 proteins

smart00964
Location:2 → 115

STAT_int; STAT protein, protein interaction domain

pfam14596
Location:655 → 847

STAT6_C; STAT6 C-terminal

pfam01017
Location:124 → 271

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:273 → 526

STAT_bind; STAT protein, DNA binding domain

RNA

NR_033659.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an alternate 5' exon compared to variant 1. This variant is represented as non-coding because use of the 5'-most supported translation start codon, as used in variant #, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC023237, AI082533, AK299094

Related

ENST00000554764.6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

57095408..57111362 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047429473.1 → XP_047285429.1 signal transducer and activator of transcription 6 isoform X1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4

Related

ENSP00000452203.2, ENST00000553397.6
XM_047429475.1 → XP_047285431.1 signal transducer and activator of transcription 6 isoform X1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4

Related

ENSP00000491116.2, ENST00000640254.2
XM_047429474.1 → XP_047285430.1 signal transducer and activator of transcription 6 isoform X1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4

Related

ENSP00000450732.2, ENST00000553275.2
XM_047429477.1 → XP_047285433.1 signal transducer and activator of transcription 6 isoform X3
XM_047429476.1 → XP_047285432.1 signal transducer and activator of transcription 6 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

57063280..57079195 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054373093.1 → XP_054229068.1 signal transducer and activator of transcription 6 isoform X1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4
XM_054373095.1 → XP_054229070.1 signal transducer and activator of transcription 6 isoform X1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4
XM_054373094.1 → XP_054229069.1 signal transducer and activator of transcription 6 isoform X1

UniProtKB/Swiss-Prot

A8K316, B7ZA27, F5GXI9, P42226, Q5FBW5, Q71UP4
XM_054373097.1 → XP_054229072.1 signal transducer and activator of transcription 6 isoform X3
XM_054373096.1 → XP_054229071.1 signal transducer and activator of transcription 6 isoform X2