Haematological malignancies cancer susceptibility
Gene: SH2B3

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

5 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: no clinical guidelines to manage the findings.
Created: 12 Mar 2026, 9:51 a.m. | Last Modified: 12 Mar 2026, 9:51 a.m.

Panel Version: 4.39

Created: 12 Mar 2026, 9:51 a.m.
Last Modified: 12 Mar 2026, 9:51 a.m.
Panel version: 4.40

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Numerous SH2B3 variants are associated with myeloproliferative neoplasms (PMID: 28484264; 27237057). In the myeloproliferative neoplasms, the SH2B3 variants can be germline or somatic within the neoplasm. Germline homozygous SH2B3 variants are also associated with acute lymphoblastic leukemia (PMID: 23908464).
Created: 12 May 2025, 4:44 p.m. | Last Modified: 12 May 2025, 4:44 p.m.

Panel Version: 4.24

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
SH2B3 associated susceptibility to acute lymphoblastic leukemia; SH2B3 associated susceptibility to myeloproliferative neoplasms

Publications

Created: 12 May 2025, 4:44 p.m.
Last Modified: 12 May 2025, 4:44 p.m.
Panel version: 4.24

Lauma Freimane (Children's Clinical University Hospital)

Green List (high evidence)

Created: 15 Jun 2023, 11:43 a.m.
Last Modified: 15 Jun 2023, 11:43 a.m.
Panel version: 4.2

Ellen McDonagh (Genomics England Curator)

Comment on publications: PMID: 23908464 - key point "SH2B3 is a recessive tumor suppressor gene with germline and somatic mutations in ALL".
Created: 30 Jan 2018, 11:53 a.m.

Comment on list classification: Demoted to amber after discussion with Clare Turnbull - does not seem to be enough evidence for this gene currently, and unclear mode of inheritance.
Created: 30 Jan 2018, 11:51 a.m.

Comment on mode of inheritance: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790510/
Created: 24 Jan 2018, 1:42 p.m.

Created: 24 Jan 2018, 1:42 p.m.

Panel version: 0.13

Clare Turnbull (Queen Mary University London)

Green List (high evidence)

Created: 26 Jul 2017, 11:15 a.m.

Panel version: 0.8

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Curated sources

Phenotypes

Class: familial predisp to leukaemia (typ AD)
SH2B3-related familial ALL
ALL
Autoimmunity
No other known cancer risks

OMIM

605093

Clinvar variants

Variants in SH2B3

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

12 Mar 2026, Gel status: 2

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_ promote_green was removed from gene: SH2B3.

1 Jul 2025, Gel status: 2

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_ MOI was removed from gene: SH2B3.

12 May 2025, Gel status: 2