SH2B2
protein-codingSH2B adaptor protein 2, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes|SH2 domain containing
Gene summary
The protein encoded by this gene is expressed in B lymphocytes and contains pleckstrin homology and src homology 2 (SH2) domains. In Burkitt's lymphoma cell lines, it is tyrosine-phosphorylated in response to B cell receptor stimulation. Because it binds Shc independent of stimulation and Grb2 after stimulation, it appears to play a role in signal transduction from the receptor to the Shc/Grb2 pathway. [provided by RefSeq, Jun 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SH2B2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001359228.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 2 | 2 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 4 | 0 | 0 | 4 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001346157.1 | 8 | MANE Select | |
| Ensembl | ENSP00000401883.3 | 8 | MANE Select | |
| RefSeq | NP_001346158.1 | 8 | Standard | |
| RefSeq | NP_001346159.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neurotrophin signaling pathway - Homo sapiens (human)
- Insulin signaling pathway - Homo sapiens (human)
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
- Kit receptor signaling pathway
- Insulin Signaling
Biological Process
- B-1 B cell homeostasis
- signal transduction
- nervous system development
- blood coagulation
- insulin receptor signaling pathway
Molecular Function
- transmembrane receptor protein tyrosine kinase adaptor activity
- SH3/SH2 adaptor activity
- protein binding
- JAK pathway signal transduction adaptor activity
- identical protein binding
Cellular Component
- stress fiber
- ruffle
- cytoplasm
- cytosol
- actin filament
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000536178
- Coding exons
- 10
- Length
- 33774
- Individuals with no LoFs
- 124667
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 124690
- p
- 0.0000922
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.84 | 237 | 331 | 0.715 | 0.0000229 | 4181 |
| Missense (PolyPhen) | 95 | 119.44 | 0.7954 | 1439 | ||
| Synonymous | 1.93 | 121 | 151 | 0.800 | 0.0000122 | 1433 |
| Loss of Function | 1.93 | 11 | 20.4 | 0.538 | 8.76e-7 | 261 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000076 | 0.000064 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000095 | 0.000093 | rare |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3. {ECO:0000269|PubMed:10374881, ECO:0000269|PubMed:12400014, ECO:0000269|PubMed:15378031, ECO:0000269|PubMed:9989826}.;
Essentials
- Essential (CRISPR2)
- S
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |