GRB2
protein-codinggrowth factor receptor bound protein 2, the group of SH2 domain containing
Gene summary
The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~87.6 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 GRB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002086.5. 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 | 1 | ||||
| missense | 8 | 8 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 10 | 0 | 1 | 11 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002077.1 | 5 | MANE Select | |
| Ensembl | ENSP00000339007.4 | 5 | MANE Select | |
| RefSeq | NP_987102.1 | 4 | Standard | |
| Ensembl | ENSP00000317360.5 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Non-small cell lung cancer - Homo sapiens (human)
- Chronic myeloid leukemia - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
Biological Process
- MAPK cascade
- epidermal growth factor receptor signaling pathway
- Ras protein signal transduction
- cell-cell signaling
- axon guidance
Molecular Function
- phosphotyrosine residue binding
- RNA binding
- SH3/SH2 adaptor activity
- Ras guanyl-nucleotide exchange factor activity
- epidermal growth factor receptor binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
- endosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392562
- Coding exons
- 5
- Length
- 87634
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125738
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.85 | 41 | 134 | 0.306 | 0.00000788 | 1454 |
| Missense (PolyPhen) | 3 | 47.203 | 0.063555 | 534 | ||
| Synonymous | 1.34 | 38 | 50.0 | 0.760 | 0.00000320 | 385 |
| Loss of Function | 3.12 | 1 | 13.3 | 0.0753 | 8.34e-7 | 125 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.;
Recessive Scores
- pRec
- 0.905
Intolerance Scores
- LoFtool
- 0.520
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |