Diabetes - neonatal onset

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 17 panels

4 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: Previous phenotypes:
Neonatal diabetes and additional multi-organ autoimmunity;permanent neonatal diabetes;Neonatal diabetes and early-onset multi-organ autoimmune disease
Created: 3 Mar 2021, 2:45 p.m. | Last Modified: 3 Mar 2021, 2:45 p.m.
Panel Version: 2.29
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: STAT3; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Neonatal diabetes and early-onset multi-organ autoimmune disease.
Created: 11 Jan 2019, 4:27 p.m.

Elisa De Franco (University of Exeter Medical School)

After the initial paper describing 4 patients, we have identified 3 additional patients with neonatal diabetes caused by a STAT3 mutation
Created: 29 May 2017, 8:34 a.m.

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as Ready: 29th May 2017.
Created: 29 May 2017, 8:51 a.m.
Comment on list classification: Updated rating from Red to Green: Green review, marked as diagnostic by Sian Ellard. Publication plus Elisa De Franco reports >3 cases of neonatal diabetes with STAT3 mutation.
Created: 29 May 2017, 8:51 a.m.
PMID:25038750 (Flanagan et al., 2014) identified a de-novo heterozygous STAT3 mutation in 1 individual with permanent neonatal diabetes (in addition to 4 individuals with polyautoimmune disease).
Created: 25 Apr 2017, 3:05 p.m.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

Gain of function mutations cause neonatal diabetes
Created: 26 Oct 2015, 10:53 p.m.

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

History Filter Activity

3 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: STAT3 were changed from Neonatal diabetes and additional multi-organ autoimmunity; permanent neonatal diabetes; Neonatal diabetes and early-onset multi-organ autoimmune disease to Autoimmune disease, multisystem, infantile-onset, 1, OMIM:615952

15 Jul 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: STAT3 were changed from Neonatal diabetes and additional multi-organ autoimmunity; permanent neonatal diabetes to Neonatal diabetes and additional multi-organ autoimmunity; permanent neonatal diabetes; Neonatal diabetes and early-onset multi-organ autoimmune disease

11 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to STAT3. Rating Changed from Green List (high evidence) to Green List (high evidence)

31 May 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

Promoted panel to Version 1: 31st May 2017. This panel is largely aligned with the Exeter Molecular Genetics Laboratory neonatal diabetes screen. Note that 8 genes feature on the Exeter 8-gene panel for patients with 'neonatal diabetes and autoimmune disease' (FOXP3, IL2RA, ITCH, LRBA, SIRT1, STAT1, STAT3 and STAT5). ITCH, SIRT1, STAT1 and STAT5A/B do not feature on this panel following correspondance with Elisa De-Franco (University of Exeter Medical School) that, at the time of curation, none of the patients with mutations in ITCH, SIRT1, STAT1 and STAT5b had diabetes diagnosed in the neonatal period, and therefore there is currently insufficient evidence to include these genes in this neonatal diabetes panel.

30 May 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for STAT3 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

30 May 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for STAT3 were set to Neonatal diabetes and additional multi-organ autoimmunity; permanent neonatal diabetes

29 May 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

29 May 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

25 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for STAT3 were set to 25038750

17 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

STAT3 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing

17 Aug 2015, Gel status: 1

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene STAT3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

17 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

STAT3 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN