FRS3
protein-codingfibroblast growth factor receptor substrate 3
Gene summary
This gene encodes a substrate for the fibroblast growth factor receptor. The encoded protein is found in the peripheral plasma membrane and links fibroblast growth factor receptor stimulation to activators of Ras. The encoded protein down-regulates extracellular regulated kinase 2 through direct binding. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.4 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 FRS3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006653.5. 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 | 0 | |||||
| missense | 88 | 2 | 2 | 92 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 90 | 2 | 2 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006644.1 | 5 | MANE Select | |
| Ensembl | ENSP00000362109.3 | 5 | MANE Select | |
| Ensembl | ENSP00000259748.2 | 5 | Standard | |
| Ensembl | ENSP00000259748.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
- FRS-mediated FGFR2 signaling
- Signaling by FGFR2
- FRS-mediated FGFR3 signaling
- Downstream signaling of activated FGFR2
Biological Process
- MAPK cascade
- signal transduction
- fibroblast growth factor receptor signaling pathway
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- fibroblast growth factor receptor binding
- protein binding
- identical protein binding
Cellular Component
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373018
- Coding exons
- 5
- Length
- 16367
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125734
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.916 | 276 | 322 | 0.856 | 0.0000210 | 3176 |
| Missense (PolyPhen) | 69 | 108.23 | 0.63753 | 1137 | ||
| Synonymous | -0.884 | 144 | 131 | 1.10 | 0.00000795 | 1041 |
| Loss of Function | 3.28 | 4 | 19.7 | 0.203 | 0.00000125 | 175 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2. {ECO:0000269|PubMed:15094036}.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.440
- RVIS EVS
- 0.29
- RVIS percentile EVS
- 71.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |