GAB2
protein-codingGRB2 associated binding protein 2, the group of Pleckstrin homology domain containing
Gene summary
This gene is a member of the GRB2-associated binding protein (GAB) gene family. These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. They act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. Two alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~203.1 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 GAB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_080491.3. 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 | 1 | 2 | 3 | |||
| missense | 105 | 1 | 2 | 108 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 108 | 2 | 4 | 114 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_536739.1 | 10 | MANE Select | |
| Ensembl | ENSP00000354952.4 | 10 | MANE Select | |
| RefSeq | NP_036428.1 | 9 | Standard | |
| Ensembl | ENSP00000343959.2 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chronic myeloid leukemia - Homo sapiens (human)
- Fc epsilon RI signaling pathway - Homo sapiens (human)
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- Sphingolipid signaling pathway - Homo sapiens (human)
Biological Process
- transmembrane receptor protein tyrosine kinase signaling pathway
- axon guidance
- positive regulation of cell population proliferation
- cytokine-mediated signaling pathway
- osteoclast differentiation
Molecular Function
- transmembrane receptor protein tyrosine kinase adaptor activity
- protein binding
- phosphatidylinositol-3,4,5-trisphosphate binding
- 1-phosphatidylinositol-3-kinase activity
- phosphatidylinositol-3,4-bisphosphate binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361507
- Coding exons
- 10
- Length
- 203052
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125747
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.622 | 426 | 391 | 1.09 | 0.0000228 | 4433 |
| Missense (PolyPhen) | 102 | 99.855 | 1.0215 | 1283 | ||
| Synonymous | 0.423 | 144 | 151 | 0.956 | 0.00000883 | 1340 |
| Loss of Function | 4.41 | 4 | 30.1 | 0.133 | 0.00000200 | 312 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis. {ECO:0000269|PubMed:15750601, ECO:0000269|PubMed:19172738}.;
Recessive Scores
- pRec
- 0.454
Intolerance Scores
- LoFtool
- 0.292
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.77
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.791
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |