Disorders of immune dysregulation

Gene: SH2B3

Green List (high evidence)

SH2B3 (SH2B adaptor protein 3)
EnsemblGeneIds (GRCh38): ENSG00000111252
EnsemblGeneIds (GRCh37): ENSG00000111252
OMIM: 605093, Gene2Phenotype
SH2B3 is in 5 panels

3 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related

Peter McNaughton (Queensland Children's Hospital)

Green List (high evidence)

2x unrelated patients with haematopoietic manifestations with predominantly myeloproliferative features. Both patients developed clinically significant extra‐haematopoietic multi‐organ autoimmune manifestations throughout life including autoimmune hypothyroidism, autoimmune hepatitis, alopecia areata and autoimmune diabetes mellitus.
Sources: Literature
Created: 26 Jul 2024, 3:43 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immune

Publications

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Created: 1 Feb 2024, 12:29 a.m. | Last Modified: 1 Feb 2024, 12:29 a.m.
Panel Version: 1.1502

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Predisposition to haematological malignancies
  • Myeloproliferation and multi-organ autoimmunity
  • juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
OMIM
605093
Clinvar variants
Variants in SH2B3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Aug 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: sh2b3 has been classified as Green List (High Evidence).

2 Aug 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SH2B3 were changed from Immune to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related

2 Aug 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: sh2b3 has been classified as Green List (High Evidence).

26 Jul 2024, Gel status: 0

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

Peter McNaughton (Queensland Children's Hospital)

gene: SH2B3 was added gene: SH2B3 was added to Disorders of immune dysregulation. Sources: Literature Mode of inheritance for gene: SH2B3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SH2B3 were set to PMID: 37206266 Phenotypes for gene: SH2B3 were set to Immune Review for gene: SH2B3 was set to GREEN