Disorders of immune dysregulation

Gene: STAT3

Green List (high evidence)

STAT3 (signal transducer and activator of transcription 3)
EnsemblGeneIds (GRCh38): ENSG00000168610
EnsemblGeneIds (GRCh37): ENSG00000168610
OMIM: 102582, Gene2Phenotype
STAT3 is in 14 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Well-established disease-gene association for hyper-IgE syndrome; identified heterozygous STAT3 variants in over 50 familial and sporadic cases; dominant-negative loss of function; multiple mouse models Hyper IgE individuals presented with the triad of staphylococcal abscesses, pneumonia with pneumatocele formation, and extremely elevated IgE.

15 unrelated families with Autoimmune disease, multisystem, infantile-onset, 1; 13 STAT3 variants identified (5 were de novo); gain of function; multiple mouse models Autoimmune disease, multisystem, infantile-onset, 1 individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature. STAT3 monoallelic variants were missense and in-frame deletions in both diseases.

(Hyper IgE- Loss of Function AND Autoimmune disease- Gain of function)
Created: 12 Aug 2021, 8:28 a.m. | Last Modified: 12 Aug 2021, 8:28 a.m.
Panel Version: 0.8776

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hyper-IgE recurrent infection syndrome MIM# 147060; Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952

Publications

Danielle Ariti (University of Melbourne)

Green List (high evidence)

18 individuals from 15 unrelated families; Multiple mouse models

All 13 heterozygous variants reported have been missense or in-frame deletions that result in a gain of function; 5 of these de novo

Individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature.
Created: 12 Aug 2021, 6:28 a.m. | Last Modified: 12 Aug 2021, 6:28 a.m.
Panel Version: 0.92

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Lymphoproliferation; solid organ autoimmunity; recurrent infections; short stature; eczema; delayed puberty; dental abnormalities; autoimmune interstitial lung disease; juvenile-onset arthritis; primary hypothyroidism

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review Green
  • Melbourne Genomics Health Alliance Immunology Flagship
  • Victorian Clinical Genetics Services
  • Victorian Clinical Genetics Services
Phenotypes
  • Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952
  • Lymphoproliferation
  • solid organ autoimmunity
  • recurrent infections
  • short stature
  • eczema
  • delayed puberty
  • dental abnormalities
  • autoimmune interstitial lung disease
  • juvenile-onset arthritis
  • primary hypothyroidism
OMIM
102582
Clinvar variants
Variants in STAT3
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

12 Aug 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: stat3 has been classified as Green List (High Evidence).

12 Aug 2021, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: STAT3 were changed from to Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Lymphoproliferation; solid organ autoimmunity; recurrent infections; short stature; eczema; delayed puberty; dental abnormalities; autoimmune interstitial lung disease; juvenile-onset arthritis; primary hypothyroidism

12 Aug 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: STAT3 were set to

12 Aug 2021, Gel status: 3

Set mode of pathogenicity

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of pathogenicity for gene: STAT3 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

12 Aug 2021, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: STAT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: STAT3 was added gene: STAT3 was added to Disorders of immune dysregulation_MGHA_AGHA_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Immunology Flagship Mode of inheritance for gene: STAT3 was set to Unknown