FRS2
fibroblast growth factor receptor substrate 2
Basic information
Region (hg38): 12:69470348-69579793
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 FRS2 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 | 0 | |||||
| missense | 27 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 27 | 0 | 0 |
Variants in FRS2
This is a list of pathogenic ClinVar variants found in the FRS2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-69569050-G-A | not specified | Uncertain significance (May 07, 2024) | ||
| 12-69570412-C-T | not specified | Uncertain significance (Sep 17, 2021) | ||
| 12-69570413-G-A | not specified | Uncertain significance (Jun 03, 2022) | ||
| 12-69570419-G-A | not specified | Uncertain significance (Sep 14, 2023) | ||
| 12-69571308-G-C | not specified | Uncertain significance (Aug 09, 2021) | ||
| 12-69571423-G-A | not specified | Uncertain significance (Jun 05, 2023) | ||
| 12-69574053-C-T | not specified | Uncertain significance (Nov 09, 2023) | ||
| 12-69574084-G-A | not specified | Uncertain significance (Apr 25, 2022) | ||
| 12-69574095-G-A | not specified | Uncertain significance (Aug 13, 2021) | ||
| 12-69574104-A-T | not specified | Uncertain significance (Feb 28, 2023) | ||
| 12-69574238-A-T | not specified | Uncertain significance (Aug 12, 2021) | ||
| 12-69574312-G-A | not specified | Uncertain significance (Jan 26, 2023) | ||
| 12-69574341-G-A | not specified | Uncertain significance (Jan 25, 2023) | ||
| 12-69574399-G-A | not specified | Uncertain significance (Oct 22, 2021) | ||
| 12-69574420-C-T | not specified | Uncertain significance (Dec 14, 2023) | ||
| 12-69574434-A-G | not specified | Uncertain significance (Dec 19, 2023) | ||
| 12-69574458-A-G | not specified | Uncertain significance (Dec 14, 2023) | ||
| 12-69574512-C-T | not specified | Uncertain significance (Aug 09, 2021) | ||
| 12-69574555-C-T | not specified | Uncertain significance (Jan 17, 2023) | ||
| 12-69574590-C-G | not specified | Uncertain significance (Apr 13, 2023) | ||
| 12-69574591-C-A | not specified | Uncertain significance (Nov 30, 2022) | ||
| 12-69574662-C-T | not specified | Uncertain significance (Jun 21, 2023) | ||
| 12-69574694-T-G | not specified | Uncertain significance (May 14, 2024) | ||
| 12-69574704-C-T | not specified | Uncertain significance (Sep 12, 2023) | ||
| 12-69574705-G-A | not specified | Uncertain significance (Jan 03, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FRS2 | protein_coding | protein_coding | ENST00000299293 | 5 | 109434 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00279 | 124776 | 0 | 5 | 124781 | 0.0000200 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.13 | 236 | 290 | 0.813 | 0.0000157 | 3330 |
| Missense in Polyphen | 50 | 86.309 | 0.57931 | 911 | ||
| Synonymous | 0.798 | 91 | 101 | 0.899 | 0.00000487 | 1010 |
| Loss of Function | 4.12 | 1 | 21.7 | 0.0461 | 0.00000142 | 242 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000581 | 0.0000581 |
| Ashkenazi Jewish | 0.000199 | 0.000199 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000887 | 0.00000883 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3- kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1. {ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:21765395}.;
- Pathway
- Neurotrophin signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Angiogenesis overview;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;VEGFA-VEGFR2 Signaling Pathway;Developmental Biology;FRS-mediated FGFR2 signaling;Negative regulation of FGFR2 signaling;Signaling by FGFR2;FRS-mediated FGFR3 signaling;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;PI-3K cascade:FGFR4;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;Signal Transduction;FRS-mediated FGFR4 signaling;Downstream signaling of activated FGFR4;Negative regulation of FGFR4 signaling;Signaling by FGFR4;Signaling by FGFR;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;FGF;Signaling by FGFR2 in disease;Fibroblast growth factor-1;Frs2-mediated activation;Prolonged ERK activation events;Signalling to ERKs;Signaling by NTRK1 (TRKA);Signaling by NTRK2 (TRKB);Signaling by NTRKs;BDNF;EGFR1;SHP2 signaling;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;Signaling events regulated by Ret tyrosine kinase;Activated NTRK2 signals through FRS2 and FRS3;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;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 FGFR in disease;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by FGFR1 in disease;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Neurotrophic factor-mediated Trk receptor signaling;Diseases of signal transduction;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);FGF signaling pathway;FRS-mediated FGFR1 signaling;PI-3K cascade:FGFR1;Negative regulation of FGFR1 signaling;Signaling by FGFR1
(Consensus)
Intolerance Scores
- loftool
- 0.180
- rvis_EVS
- -0.27
- rvis_percentile_EVS
- 34.6
Haploinsufficiency Scores
- pHI
- 0.939
- hipred
- Y
- hipred_score
- 0.699
- ghis
- 0.527
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.677
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Frs2
- Phenotype
- embryo 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); 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); limbs/digits/tail phenotype; hearing/vestibular/ear 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); vision/eye phenotype; skeleton phenotype; renal/urinary system phenotype; growth/size/body region phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- MAPK cascade;activation of MAPKK activity;activation of MAPK activity;gastrulation with mouth forming second;organ induction;ventricular septum development;transmembrane receptor protein tyrosine phosphatase signaling pathway;G protein-coupled receptor signaling pathway;neuroblast proliferation;axon guidance;fibroblast growth factor receptor signaling pathway;anterior/posterior axis specification, embryo;forebrain development;phosphatidylinositol-3-phosphate biosynthetic process;regulation of apoptotic process;optic placode formation involved in camera-type eye formation;phosphatidylinositol phosphorylation;neurotrophin TRK receptor signaling pathway;regulation of epithelial cell proliferation;positive regulation of protein kinase B signaling;prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis;lens fiber cell development;regulation of ERK1 and ERK2 cascade;negative regulation of cardiac muscle cell differentiation
- Cellular component
- cytosol;plasma membrane;integral component of plasma membrane;cell-cell adherens junction;endomembrane system;membrane
- Molecular function
- transmembrane receptor protein tyrosine kinase adaptor activity;Ras guanyl-nucleotide exchange factor activity;fibroblast growth factor receptor binding;neurotrophin TRKA receptor binding;protein binding;1-phosphatidylinositol-3-kinase activity;phosphatase activator activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity