FER
protein-codingFER tyrosine kinase, the group of Fes family tyrosine kinases|Protein phosphatase 1 regulatory subunits|SH2 domain containing|F-BAR domain containing
Gene summary
The protein encoded by this gene is a member of the FPS/FES family of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion and mediates signaling from the cell surface to the cytoskeleton via growth factor receptors. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Apr 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~449.0 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 FER variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005246.4. 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 | 2 | 1 | 3 | 6 | ||
| missense | 75 | 4 | 1 | 80 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 82 | 5 | 4 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005237.2 | 18 | MANE Select | |
| Ensembl | ENSP00000281092.4 | 18 | MANE Select | |
| RefSeq | NP_001294957.1 | 15 | Standard | |
| RefSeq | NP_001294960.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| fer | Danio rerio | Structure: ceratohyal cartilage Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adherens junction - Homo sapiens (human)
- Signal Transduction
- TCR
- Signaling by SCF-KIT
- Signaling by Receptor Tyrosine Kinases
Biological Process
- microtubule cytoskeleton organization
- mitotic cell cycle
- regulation of protein phosphorylation
- protein phosphorylation
- chemotaxis
Molecular Function
- protein tyrosine kinase activity
- non-membrane spanning protein tyrosine kinase activity
- epidermal growth factor receptor binding
- protein binding
- ATP binding
Cellular Component
- nuclear chromatin
- nucleus
- cytoplasm
- cytosol
- cell cortex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000281092
- Coding exons
- 18
- Length
- 449020
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125735
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.26 | 339 | 411 | 0.825 | 0.0000198 | 5442 |
| Missense (PolyPhen) | 115 | 168.26 | 0.68346 | 2180 | ||
| Synonymous | -0.749 | 152 | 141 | 1.08 | 0.00000719 | 1410 |
| Loss of Function | 5.04 | 10 | 47.5 | 0.211 | 0.00000235 | 612 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00025 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00021 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus. {ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:14517306, ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:19738202, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21518868, ECO:0000269|PubMed:22223638, ECO:0000269|PubMed:7623846, ECO:0000269|PubMed:9722593}.;
Recessive Scores
- pRec
- 0.144
Intolerance Scores
- LoFtool
- 0.254
- RVIS EVS
- -0.44
- RVIS percentile EVS
- 24.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.787
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |