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Primary immunodeficiency

Gene: IL6ST

Amber List (moderate evidence)

IL6ST (interleukin 6 signal transducer)
EnsemblGeneIds (GRCh38): ENSG00000134352
EnsemblGeneIds (GRCh37): ENSG00000134352
OMIM: 600694, Gene2Phenotype
IL6ST is in 2 panels

6 reviews

Eleanor Williams (Genomics England Curator)

PMID: 33517393 - Materna-Kiryluk et al 2021 - describe a patient with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphic features. The patient was found using exome sequencing to have a de novo IL6ST Tyr186_Tyr190del variant, which was present as a mosaic. It was found in around 15–40% of cells depending on the tissue (blood, urine sediment, hair bulbs and buccal swab).
Created: 4 May 2021, 6:26 p.m. | Last Modified: 4 May 2021, 6:26 p.m.
Panel Version: 2.419

Publications

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Created: 20 Oct 2020, 3:05 p.m. | Last Modified: 20 Oct 2020, 3:05 p.m.
Panel Version: 2.342

Sarah Leigh (Genomics England Curator)

Comment on list classification: Based on expert review and the reporting of additional variants.
Created: 5 May 2020, 4:07 p.m. | Last Modified: 5 May 2020, 4:07 p.m.
Panel Version: 2.158
Comment on phenotypes: Eosinophilia;Eczema;Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis;Abnormal acute-phase responses;Recurrent infections;Elevated IgE;Combined immunodeficiencies with associated or syndromic features
Created: 5 May 2020, 4:03 p.m. | Last Modified: 5 May 2020, 4:03 p.m.
Panel Version: 2.157

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed.
Created: 10 Apr 2020, 8:20 a.m. | Last Modified: 10 Apr 2020, 8:20 a.m.
Panel Version: 2.51

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.; Hyper-IgE syndrome, autosomal dominant

Publications

Louise Daugherty (Genomics England Curator)

I don't know

Added publication referenced by IUIS december 2019 update
Created: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Comment on list classification: New gene added for review
Created: 26 Feb 2020, 4:30 p.m. | Last Modified: 26 Feb 2020, 4:30 p.m.
Panel Version: 2.5
New gene suggested by expert reviewer- unable to do a full curational review (Green rating recommended) as we are waiting for new PanelApp features before this gene can be added to this GMS panel.
Created: 22 Jan 2020, 11:36 a.m. | Last Modified: 22 Jan 2020, 11:36 a.m.
Panel Version: 2.0

Publications

Owen Siggs (Flinders University)

Green List (high evidence)

At least two unrelated cases with homozygous loss-of-function variants and compelling functional support.
Created: 18 Jan 2020, 7:44 a.m. | Last Modified: 18 Jan 2020, 7:44 a.m.
Panel Version: 2.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyper-IgE syndrome

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • IUIS Classification December 2019
Phenotypes
  • Hyper-IgE recurrent infection syndrome 4, autosomal recessive 618523
  • Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.
  • Hyper-IgE syndrome, autosomal dominant
Tags
for-review
OMIM
600694
Clinvar variants
Variants in IL6ST
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: il6st has been classified as Amber List (Moderate Evidence).

20 Oct 2020, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: IL6ST.

5 May 2020, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: il6st has been classified as Green List (High Evidence).

5 May 2020, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: IL6ST were changed from Eosinophilia; Eczema; Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis; Abnormal acute-phase responses; Recurrent infections; Elevated IgE; Combined immunodeficiencies with associated or syndromic features to Hyper-IgE recurrent infection syndrome 4, autosomal recessive 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.; Hyper-IgE syndrome, autosomal dominant

5 May 2020, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: IL6ST were set to 31235509; 32086639; 30309848; 28747427; 32048120

28 Feb 2020, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene IL6ST were updated from 32048120; 31235509; 32086639 to 31235509; 32086639; 30309848; 28747427; 32048120

28 Feb 2020, Gel status: 1

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to IL6ST. Added phenotypes Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis; Combined immunodeficiencies with associated or syndromic features for gene: IL6ST Publications for gene IL6ST were updated from 31235509 to 32048120; 31235509; 32086639

26 Feb 2020, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: il6st has been classified as Red List (Low Evidence).

18 Jan 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Owen Siggs (Flinders University)

gene: IL6ST was added gene: IL6ST was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL6ST were set to 31235509 Phenotypes for gene: IL6ST were set to Recurrent infections; Abnormal acute-phase responses; Elevated IgE; Eczema; Eosinophilia Review for gene: IL6ST was set to GREEN