FGR
FGR proto-oncogene, Src family tyrosine kinase, the group of SH2 domain containing|Src family tyrosine kinases
Basic information
Region (hg38): 1:27612064-27635185
Previous symbols: [ "SRC2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGR 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 | 2 | |||||
| missense | 24 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 24 | 4 | 2 |
Variants in FGR
This is a list of pathogenic ClinVar variants found in the FGR region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-27612931-G-A | Uncertain significance (Nov 04, 2020) | |||
| 1-27612942-G-A | not specified | Uncertain significance (Feb 12, 2024) | ||
| 1-27613015-G-C | not specified | Uncertain significance (May 15, 2023) | ||
| 1-27613018-G-A | not specified | Uncertain significance (Aug 27, 2024) | ||
| 1-27613111-G-A | not specified | Uncertain significance (Apr 22, 2022) | ||
| 1-27613221-G-A | not specified | Uncertain significance (Feb 17, 2024) | ||
| 1-27613249-G-A | not specified | Uncertain significance (May 09, 2022) | ||
| 1-27613273-A-G | not specified | Uncertain significance (Jun 24, 2022) | ||
| 1-27613278-A-C | not specified | Uncertain significance (Apr 05, 2023) | ||
| 1-27614495-G-A | not specified | Likely benign (May 26, 2024) | ||
| 1-27614496-C-T | not specified | Uncertain significance (Mar 27, 2023) | ||
| 1-27615472-T-G | not specified | Uncertain significance (Feb 11, 2022) | ||
| 1-27615524-T-A | not specified | Uncertain significance (Jun 03, 2022) | ||
| 1-27615592-T-G | not specified | Uncertain significance (Jul 25, 2023) | ||
| 1-27615596-T-C | not specified | Uncertain significance (Mar 28, 2024) | ||
| 1-27615753-G-C | not specified | Uncertain significance (Mar 28, 2024) | ||
| 1-27615765-G-A | Benign (Feb 18, 2020) | |||
| 1-27616864-G-C | not specified | Uncertain significance (Sep 14, 2022) | ||
| 1-27616889-T-C | not specified | Likely benign (May 23, 2023) | ||
| 1-27617014-G-C | Benign (Mar 29, 2018) | |||
| 1-27617243-G-A | not specified | Uncertain significance (Apr 04, 2023) | ||
| 1-27617254-C-G | not specified | Uncertain significance (Nov 22, 2023) | ||
| 1-27617279-A-G | not specified | Uncertain significance (Nov 08, 2024) | ||
| 1-27621621-G-A | Benign (Feb 08, 2018) | |||
| 1-27621635-G-A | Uncertain significance (Nov 04, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FGR | protein_coding | protein_coding | ENST00000374005 | 11 | 23214 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.484 | 0.516 | 125722 | 0 | 26 | 125748 | 0.000103 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.78 | 189 | 331 | 0.570 | 0.0000201 | 3453 |
| Missense in Polyphen | 75 | 156.56 | 0.47904 | 1617 | ||
| Synonymous | 1.75 | 112 | 138 | 0.810 | 0.00000911 | 1023 |
| Loss of Function | 3.84 | 6 | 27.8 | 0.216 | 0.00000144 | 300 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.000416 | 0.000416 |
| European (Non-Finnish) | 0.0000440 | 0.0000439 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000298 | 0.000294 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK- dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. {ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}.;
- Disease
- DISEASE: Note=Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.;
- Pathway
- Chemokine signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Focal Adhesion;Chemokine signaling pathway;Neutrophil degranulation;Innate Immune System;Immune System;KitReceptor;roles of arrestin dependent recruitment of src kinases in gpcr signaling;CXCR4-mediated signaling events;Hemostasis;Thromboxane A2 receptor signaling;Ephrin B reverse signaling;Class I PI3K signaling events;IL6;Platelet sensitization by LDL;Platelet homeostasis;Glypican 1 network;IL8- and CXCR1-mediated signaling events;Regulation of p38-alpha and p38-beta;Alpha-synuclein signaling;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;IL8- and CXCR2-mediated signaling events;EPHA forward signaling
(Consensus)
Recessive Scores
- pRec
- 0.607
Intolerance Scores
- loftool
- 0.222
- rvis_EVS
- -0.89
- rvis_percentile_EVS
- 10.3
Haploinsufficiency Scores
- pHI
- 0.514
- hipred
- Y
- hipred_score
- 0.722
- ghis
- 0.642
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fgr
- Phenotype
- skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; normal phenotype; 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; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- immune response-regulating cell surface receptor signaling pathway;protein phosphorylation;transmembrane receptor protein tyrosine kinase signaling pathway;integrin-mediated signaling pathway;regulation of cell shape;response to virus;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-tyrosine phosphorylation;cell differentiation;positive regulation of cell migration;peptidyl-tyrosine autophosphorylation;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of mast cell degranulation;neutrophil degranulation;positive regulation of phosphatidylinositol 3-kinase activity;innate immune response;regulation of innate immune response;regulation of protein kinase activity;protein autophosphorylation;positive regulation of cytokine secretion;regulation of phagocytosis;defense response to Gram-positive bacterium
- Cellular component
- extracellular region;mitochondrial inner membrane;mitochondrial intermembrane space;cytosol;cytoskeleton;plasma membrane;actin cytoskeleton;aggresome;extrinsic component of cytoplasmic side of plasma membrane;ruffle membrane;secretory granule lumen;extracellular exosome
- Molecular function
- phosphotyrosine residue binding;protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;signaling receptor binding;protein binding;ATP binding;protein kinase binding;immunoglobulin receptor binding;Fc-gamma receptor I complex binding