GRB10
protein-codinggrowth factor receptor bound protein 10, the group of SH2 domain containing|Pleckstrin homology domain containing
Gene summary
The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~203.4 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 GRB10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001350814.2. 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 | 7 | 2 | 9 | |||
| missense | 49 | 4 | 4 | 57 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 59 | 11 | 6 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001337743.1 | 16 | MANE Select | |
| Ensembl | ENSP00000385770.1 | 16 | MANE Select | |
| RefSeq | NP_001001549.1 | 15 | Standard | |
| RefSeq | NP_001001550.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- IGF-Ncore
- Kit receptor signaling pathway
- PI3K-AKT-mTOR signaling pathway and therapeutic opportunities
- VEGFA-VEGFR2 Signaling Pathway
Biological Process
- axon guidance
- negative regulation of Wnt signaling pathway
- positive regulation of vascular endothelial growth factor receptor signaling pathway
- negative regulation of phosphorylation
- negative regulation of glucose import
Molecular Function
- SH3/SH2 adaptor activity
- insulin receptor binding
- protein binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398812
- Coding exons
- 16
- Length
- 203400
- Individuals with no LoFs
- 124776
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 124796
- p
- 0.0000801
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.53 | 255 | 334 | 0.764 | 0.0000207 | 3916 |
| Missense (PolyPhen) | 33 | 93.263 | 0.35384 | 1077 | ||
| Synonymous | 0.0592 | 138 | 139 | 0.994 | 0.00000947 | 1123 |
| Loss of Function | 4.57 | 6 | 35.3 | 0.170 | 0.00000182 | 387 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00032 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin- stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin- stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2. {ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:16434550, ECO:0000269|PubMed:17376403}.;
Recessive Scores
- pRec
- 0.674
Intolerance Scores
- LoFtool
- 0.197
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 43.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.876
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |