GRB2
growth factor receptor bound protein 2, the group of SH2 domain containing
Basic information
Region (hg38): 17:75318075-75405709
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1 variants)
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRB2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 1 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 1 | 0 | 1 |
Variants in GRB2
This is a list of pathogenic ClinVar variants found in the GRB2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-75321730-C-T | not specified | Uncertain significance (Nov 12, 2021) | ||
| 17-75325960-G-A | Benign (Dec 31, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GRB2 | protein_coding | protein_coding | ENST00000392562 | 5 | 87634 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.939 | 0.0606 | 125736 | 0 | 2 | 125738 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.85 | 41 | 134 | 0.306 | 0.00000788 | 1454 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.00000880 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.;
- Pathway
- 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);mTOR signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Gap junction - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;Insulin Signalling;IL-5 Signaling Pathway;Angiogenesis overview;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Prolactin Signaling Pathway;IL-9 Signaling Pathway;Pilocytic astrocytoma;Signaling Pathways in Glioblastoma;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;Interleukin-11 Signaling Pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Alpha 6 Beta 4 signaling pathway;JAK-STAT;IL-3 Signaling Pathway;nerve growth factor pathway (ngf);Kit receptor signaling pathway;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;Rac1-Pak1-p38-MMP-2 pathway;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;TGF-beta Signaling Pathway;BDNF-TrkB Signaling;Association Between Physico-Chemical Features and Toxicity Associated Pathways;MAPK Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PDGFR-beta pathway;miRNA regulation of prostate cancer signaling pathways;p38 MAPK Signaling Pathway;Endometrial cancer;PI3K-Akt Signaling Pathway;MET in type 1 papillary renal cell carcinoma;Ras Signaling;EMT transition in Colorectal Cancer;EGF-EGFR Signaling Pathway;Insulin Signaling;IL-2 Signaling Pathway;EPO Receptor Signaling;ErbB Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;DNA Damage Response (only ATM dependent);SHC1 events in ERBB2 signaling;Developmental Biology;Signaling by GPCR;FRS-mediated FGFR2 signaling;Negative regulation of FGFR2 signaling;Signaling by FGFR2;Regulation of Ras family activation;SHC-mediated cascade:FGFR2;FRS-mediated FGFR3 signaling;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;SHC-mediated cascade:FGFR3;PI-3K cascade:FGFR4;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;Signal Transduction;FRS-mediated FGFR4 signaling;SHC-mediated cascade:FGFR4;Downstream signaling of activated FGFR4;Signaling by Interleukins;DAP12 signaling;DAP12 interactions;Negative regulation of FGFR4 signaling;Signaling by FGFR4;Signaling by FGFR;inhibition of cellular proliferation by gleevec;Spry regulation of FGF signaling;bioactive peptide induced signaling pathway;role of erk5 in neuronal survival pathway;the co-stimulatory signal during t-cell activation;Vesicle-mediated transport;links between pyk2 and map kinases;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;egf signaling pathway;il 2 signaling pathway;trefoil factors initiate mucosal healing;transcription factor creb and its extracellular signals;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;integrin signaling pathway;il-2 receptor beta chain in t cell activation;phospholipids as signalling intermediaries;il 4 signaling pathway;multiple antiapoptotic pathways from igf-1r signaling lead to bad phosphorylation;pten dependent cell cycle arrest and apoptosis;vegf hypoxia and angiogenesis;mcalpain and friends in cell motility;nfat and hypertrophy of the heart ;il 6 signaling pathway;sprouty regulation of tyrosine kinase signals;cbl mediated ligand-induced downregulation of egf receptors pathway;phosphorylation of mek1 by cdk5/p35 down regulates the map kinase pathway;trka receptor signaling pathway;insulin signaling pathway;t cell receptor signaling pathway;Membrane Trafficking;bcr signaling pathway;calcium signaling by hbx of hepatitis b virus;erk1/erk2 mapk signaling pathway;role of erbb2 in signal transduction and oncology;keratinocyte differentiation;Prolactin;Cytokine Signaling in Immune system;map kinase inactivation of smrt corepressor;Alpha6Beta4Integrin;B cell receptor signaling;Signal attenuation;CD28 dependent Vav1 pathway;CD28 co-stimulation;PI3K Cascade;Costimulation by the CD28 family;SOS-mediated signalling;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Signaling by the B Cell Receptor (BCR);SHC1 events in EGFR signaling;Signaling by PDGF;CD4 T cell receptor signaling-ERK cascade;igf-1 signaling pathway;Fcgamma receptor (FCGR) dependent phagocytosis;GRB2:SOS provides linkage to MAPK signaling for Integrins ;Integrin alphaIIb beta3 signaling;il 3 signaling pathway;HGF;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Infectious disease;Oncostatin_M;IGF signaling;Innate Immune System;Immune System;Interleukin-15 signaling;Ghrelin;RHO GTPases Activate WASPs and WAVEs;FGF;Interleukin receptor SHC signaling;Interleukin-2 family signaling;IL5-mediated signaling events;Signaling by FGFR2 in disease;Adaptive Immune System;KitReceptor;Fibroblast growth factor-1;insulin Mam;MET activates RAP1 and RAC1;BCR;ErbB4 signaling events;pdgf signaling pathway;EGFR downregulation;Signaling by EGFR;epo signaling pathway;Platelet Aggregation (Plug Formation);Signalling to RAS;Platelet activation, signaling and aggregation;Regulation of KIT signaling;RHO GTPase Effectors;Signaling by Rho GTPases;tpo signaling pathway;Clathrin-mediated endocytosis;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;fc epsilon receptor i signaling in mast cells;Activated NTRK2 signals through RAS;Signaling by NTRK2 (TRKB);Signaling by NTRKs;BDNF;EGFR1;SHP2 signaling;Tie2 Signaling;Integrin signaling;growth hormone signaling pathway;ErbB1 downstream signaling;Cell surface interactions at the vascular wall;Hemostasis;GAB1 signalosome;the igf-1 receptor and longevity;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;BCR signaling pathway;Signaling events mediated by TCPTP;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PDGF;IL2;GRB2 events in ERBB2 signaling;Regulation of actin dynamics for phagocytic cup formation;EGFR Transactivation by Gastrin;NCAM signaling for neurite out-growth;VEGFR3 signaling in lymphatic endothelium;NGF;Signaling events regulated by Ret tyrosine kinase;IL3;a6b1 and a6b4 Integrin signaling;IL2-mediated signaling events;Gastrin;Downstream signal transduction;Cargo recognition for clathrin-mediated endocytosis;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by EGFRvIII in Cancer;Signaling by EGFR in Cancer;Angiopoietin receptor Tie2-mediated signaling;EGFR-dependent Endothelin signaling events;GRB2 events in EGFR signaling;IL4;EPO signaling pathway;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR4 in disease;RET signaling;Axon guidance;Signaling by FGFR3 fusions in cancer;Signaling by FGFR3 in disease;Signaling by SCF-KIT;Signaling by FGFR in disease;IL5;Leptin;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K events in ERBB2 signaling;Signaling by ERBB2;SHC1 events in ERBB4 signaling;PI3K/AKT Signaling in Cancer;Signaling by ERBB4;IL6;SHC-related events triggered by IGF1R;IRS-related events triggered by IGF1R;IGF1R signaling cascade;TNFalpha;MET activates RAS signaling;MET activates PI3K/AKT signaling;MET promotes cell motility;Signaling by cytosolic FGFR1 fusion mutants;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Negative regulation of MET activity;Signaling by MET;Constitutive Signaling by EGFRvIII;Signaling by Receptor Tyrosine Kinases;Signal regulatory protein family interactions;Cell-Cell communication;Gastrin-CREB signalling pathway via PKC and MAPK;G alpha (q) signalling events;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Signaling by Ligand-Responsive EGFR Variants in Cancer;EGF;MET activates PTPN11;ErbB2/ErbB3 signaling events;Intracellular signaling by second messengers;GMCSF-mediated signaling events;IL2 signaling events mediated by STAT5;Insulin Pathway;Neurotrophic factor-mediated Trk receptor signaling;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;Internalization of ErbB1;Signaling events mediated by focal adhesion kinase;IL2 signaling events mediated by PI3K;TCR signaling in naïve CD8+ T cells;EPHB forward signaling;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);Plasma membrane estrogen receptor signaling;Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;IL4-mediated signaling events;Signaling events mediated by PTP1B;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);EPHA2 forward signaling;IL6-mediated signaling events;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;Nephrin/Neph1 signaling in the kidney podocyte;PDGFR-alpha signaling pathway;IL3-mediated signaling events;TGF-beta receptor signaling;FRS-mediated FGFR1 signaling;Role of LAT2/NTAL/LAB on calcium mobilization;SHC-mediated cascade:FGFR1;insulin;PI-3K cascade:FGFR1;Negative regulation of FGFR1 signaling;Signaling by FGFR1;CD4 T cell receptor signaling;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling;InlB-mediated entry of Listeria monocytogenes into host cell;Listeria monocytogenes entry into host cells
(Consensus)
Recessive Scores
- pRec
- 0.905
Intolerance Scores
- loftool
- 0.520
- rvis_EVS
- -0.12
- rvis_percentile_EVS
- 44.54
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.596
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Grb2
- Phenotype
- craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; normal phenotype; endocrine/exocrine gland phenotype; neoplasm; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- MAPK cascade;epidermal growth factor receptor signaling pathway;Ras protein signal transduction;cell-cell signaling;axon guidance;aging;insulin receptor signaling pathway;fibroblast growth factor receptor signaling pathway;viral process;cytokine-mediated signaling pathway;positive regulation of actin filament polymerization;T cell costimulation;receptor internalization;entry of bacterium into host cell;interleukin-15-mediated signaling pathway;phosphatidylinositol-3-phosphate biosynthetic process;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;ERBB2 signaling pathway;negative regulation of epidermal growth factor receptor signaling pathway;signal transduction in response to DNA damage;regulation of MAPK cascade;positive regulation of Ras protein signal transduction;phosphatidylinositol phosphorylation;neurotrophin TRK receptor signaling pathway;anatomical structure formation involved in morphogenesis;leukocyte migration;protein heterooligomerization;positive regulation of protein kinase B signaling;branching involved in labyrinthine layer morphogenesis;membrane organization;cellular response to ionizing radiation;positive regulation of reactive oxygen species metabolic process
- Cellular component
- nucleus;nucleoplasm;nucleolus;cytoplasm;endosome;Golgi apparatus;cytosol;plasma membrane;cell-cell junction;COP9 signalosome;vesicle membrane;extracellular exosome;Grb2-EGFR complex
- Molecular function
- phosphotyrosine residue binding;RNA binding;SH3/SH2 adaptor activity;Ras guanyl-nucleotide exchange factor activity;epidermal growth factor receptor binding;neurotrophin TRKA receptor binding;protein binding;1-phosphatidylinositol-3-kinase activity;SH3 domain binding;protein kinase binding;protein phosphatase binding;identical protein binding;insulin receptor substrate binding;ephrin receptor binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity