FYN
FYN proto-oncogene, Src family tyrosine kinase, the group of SH2 domain containing|Src family tyrosine kinases
Basic information
Region (hg38): 6:111660331-111873452
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (12 variants)
- Inborn genetic diseases (10 variants)
- Premature ovarian failure (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FYN 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 | 11 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 2 | 2 | ||||
| non coding ? | 1 | |||||
| Total | 0 | 0 | 11 | 0 | 4 |
Variants in FYN
This is a list of pathogenic ClinVar variants found in the FYN region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-111661801-T-C | not specified | Likely benign (Nov 02, 2023) | ||
| 6-111661835-G-C | Benign (Nov 01, 2022) | |||
| 6-111674557-C-T | not provided (-) | |||
| 6-111694367-G-A | Benign (Jun 15, 2018) | |||
| 6-111694444-G-A | not specified | Uncertain significance (Dec 13, 2021) | ||
| 6-111694538-C-T | Benign (Jul 13, 2018) | |||
| 6-111694620-G-T | Benign (Jul 13, 2018) | |||
| 6-111694644-A-G | not specified | Uncertain significance (Feb 28, 2023) | ||
| 6-111696335-C-T | not provided (-) | |||
| 6-111696350-G-A | Benign (May 01, 2018) | |||
| 6-111696375-G-C | not provided (-) | |||
| 6-111696400-A-C | not specified | Uncertain significance (Jul 14, 2021) | ||
| 6-111699574-C-T | not provided (-) | |||
| 6-111700152-G-C | not specified | Uncertain significance (May 24, 2023) | ||
| 6-111700267-C-G | not specified | Uncertain significance (Mar 16, 2023) | ||
| 6-111703009-A-G | not provided (-) | |||
| 6-111707998-G-A | not specified | Uncertain significance (May 04, 2022) | ||
| 6-111714358-T-C | not provided (-) | |||
| 6-111714417-C-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 6-111719846-G-C | Premature ovarian failure | Uncertain significance (Mar 02, 2020) | ||
| 6-111719865-C-T | not specified | Uncertain significance (Jun 11, 2021) | ||
| 6-111719868-T-C | not specified | Uncertain significance (Oct 02, 2023) | ||
| 6-111719889-C-T | not specified | Uncertain significance (May 13, 2022) | ||
| 6-111719926-G-A | Benign (Aug 16, 2018) | |||
| 6-111720028-A-T | not specified | Uncertain significance (May 09, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FYN | protein_coding | protein_coding | ENST00000354650 | 11 | 213121 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00594 | 125740 | 0 | 8 | 125748 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.03 | 114 | 316 | 0.361 | 0.0000179 | 3495 |
| Missense in Polyphen | 46 | 177.08 | 0.25977 | 1947 | ||
| Synonymous | 0.112 | 120 | 122 | 0.987 | 0.00000720 | 1037 |
| Loss of Function | 4.67 | 4 | 32.9 | 0.122 | 0.00000195 | 350 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000119 | 0.000119 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000352 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta- catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. {ECO:0000269|PubMed:11005864, ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11536198, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:14707117, ECO:0000269|PubMed:14761972, ECO:0000269|PubMed:15536091, ECO:0000269|PubMed:15557120, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:16841086, ECO:0000269|PubMed:17194753, ECO:0000269|PubMed:18056706, ECO:0000269|PubMed:18258597, ECO:0000269|PubMed:19179337, ECO:0000269|PubMed:19652227, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:7568038, ECO:0000269|PubMed:7822789}.;
- Pathway
- Prion diseases - Homo sapiens (human);Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Adherens junction - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Axon guidance - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;EGF-Ncore;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Prolactin Signaling Pathway;IL-7 Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Pathogenic Escherichia coli infection;B Cell Receptor Signaling Pathway;Interleukin-11 Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Primary Focal Segmental Glomerulosclerosis FSGS;T-Cell Receptor and Co-stimulatory Signaling;JAK-STAT;Ectoderm Differentiation;IL-3 Signaling Pathway;Kit receptor signaling pathway;Focal Adhesion;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;VEGFA-VEGFR2 Signaling Pathway;Prion disease pathway;IL-2 Signaling Pathway;Interferon type I signaling pathways;T-Cell antigen Receptor (TCR) Signaling Pathway;Developmental Biology;Disease;Signal Transduction;Signaling by Interleukins;DAP12 signaling;DAP12 interactions;bioactive peptide induced signaling pathway;il-7 signal transduction;tsp-1 induced apoptosis in microvascular endothelial cell;integrin signaling pathway;lck and fyn tyrosine kinases in initiation of tcr activation;role of mef2d in t-cell apoptosis;VEGFA-VEGFR2 Pathway;t cell receptor signaling pathway;Prolactin;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;Host Interactions of HIV factors;HIV Infection;B cell receptor signaling;CD28 dependent PI3K/Akt signaling;CD28 dependent Vav1 pathway;CD28 co-stimulation;CTLA4 inhibitory signaling;Costimulation by the CD28 family;Dectin-2 family;C-type lectin receptors (CLRs);EPH-Ephrin signaling;Fc epsilon receptor (FCERI) signaling;TCR;EPHA-mediated growth cone collapse;Infectious disease;Innate Immune System;Immune System;EPHB-mediated forward signaling;Ghrelin;Ephrin signaling;EPH-ephrin mediated repulsion of cells;Adaptive Immune System;KitReceptor;BCR;Platelet Adhesion to exposed collagen;ErbB4 signaling events;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;IL-7 signaling;Regulation of KIT signaling;DCC mediated attractive signaling;Integrin;Netrin mediated repulsion signals;Activated NTRK2 signals through FYN;Signaling by NTRK2 (TRKB);Signaling by NTRKs;Nef and signal transduction;EGFR1;PECAM1 interactions;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;CXCR4-mediated signaling events;Sema3A PAK dependent Axon repulsion;Cell surface interactions at the vascular wall;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Semaphorin interactions;Thromboxane A2 receptor signaling;PIP3 activates AKT signaling;JAK STAT pathway and regulation;IL2;The role of Nef in HIV-1 replication and disease pathogenesis;NCAM signaling for neurite out-growth;E-cadherin signaling in keratinocytes;Posttranslational regulation of adherens junction stability and dissassembly;EPO signaling;Netrin-1 signaling;Ephrin A reverse signaling;IL2-mediated signaling events;Ephrin B reverse signaling;Class I PI3K signaling events;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by VEGF;Angiopoietin receptor Tie2-mediated signaling;Axon guidance;Signaling by SCF-KIT;Leptin;Constitutive Signaling by Aberrant PI3K in Cancer;Signaling by ERBB2;PI3K/AKT Signaling in Cancer;CRMPs in Sema3A signaling;IL6;IL-7;Reelin signalling pathway;Signaling by Receptor Tyrosine Kinases;VEGF;Nephrin family interactions;Cell-Cell communication;Intracellular signaling by second messengers;Diseases of signal transduction;Glypican 1 network;Fc-epsilon receptor I signaling in mast cells;Netrin-mediated signaling events;Signaling events mediated by focal adhesion kinase;TCR signaling in naïve CD8+ T cells;Reelin signaling pathway;Regulation of p38-alpha and p38-beta;Alpha-synuclein signaling;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;Nephrin/Neph1 signaling in the kidney podocyte;EPHA forward signaling;Syndecan-3-mediated signaling events;CD4 T cell receptor signaling-NFkB cascade;Role of LAT2/NTAL/LAB on calcium mobilization;CD4 T cell receptor signaling;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.838
Intolerance Scores
- loftool
- 0.167
- rvis_EVS
- -0.54
- rvis_percentile_EVS
- 20.54
Haploinsufficiency Scores
- pHI
- 0.995
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.560
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fyn
- 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; taste/olfaction phenotype; cellular phenotype; homeostasis/metabolism phenotype; vision/eye 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system 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);
Gene ontology
- Biological process
- MAPK cascade;response to singlet oxygen;neuron migration;stimulatory C-type lectin receptor signaling pathway;adaptive immune response;heart process;protein phosphorylation;calcium ion transport;transmembrane receptor protein tyrosine kinase signaling pathway;axon guidance;blood coagulation;learning;feeding behavior;regulation of cell shape;negative regulation of gene expression;negative regulation of hydrogen peroxide biosynthetic process;positive regulation of neuron projection development;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;cell differentiation;platelet activation;forebrain development;T cell costimulation;negative regulation of protein ubiquitination;intracellular signal transduction;cellular response to platelet-derived growth factor stimulus;peptidyl-tyrosine autophosphorylation;Fc-gamma receptor signaling pathway involved in phagocytosis;negative regulation of protein catabolic process;positive regulation of tyrosine phosphorylation of STAT protein;response to hydrogen peroxide;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of neuron apoptotic process;response to ethanol;phosphatidylinositol phosphorylation;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;dendrite morphogenesis;regulation of defense response to virus by virus;regulation of peptidyl-tyrosine phosphorylation;activated T cell proliferation;modulation of chemical synaptic transmission;T cell receptor signaling pathway;leukocyte migration;detection of mechanical stimulus involved in sensory perception of pain;positive regulation of protein kinase B signaling;cellular response to peptide hormone stimulus;cellular response to transforming growth factor beta stimulus;positive regulation of protein targeting to membrane;dendritic spine maintenance;positive regulation of protein localization to nucleus;regulation of glutamate receptor signaling pathway;positive regulation of neuron death;negative regulation of dendritic spine maintenance;negative regulation of oxidative stress-induced cell death;positive regulation of non-membrane spanning protein tyrosine kinase activity;response to amyloid-beta;cellular response to L-glutamate;cellular response to glycine;positive regulation of protein localization to membrane;regulation of calcium ion import across plasma membrane;positive regulation of cysteine-type endopeptidase activity;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- Cellular component
- nucleus;mitochondrion;endosome;cytosol;actin filament;plasma membrane;postsynaptic density;dendrite;extrinsic component of cytoplasmic side of plasma membrane;cell body;membrane raft;perinuclear region of cytoplasm;perinuclear endoplasmic reticulum;glial cell projection;Schaffer collateral - CA1 synapse;glutamatergic synapse;postsynaptic density, intracellular component
- Molecular function
- protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;signaling receptor binding;protein binding;ATP binding;enzyme binding;type 5 metabotropic glutamate receptor binding;T cell receptor binding;CD4 receptor binding;CD8 receptor binding;identical protein binding;alpha-tubulin binding;phosphatidylinositol 3-kinase binding;ion channel binding;metal ion binding;ephrin receptor binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;tau protein binding;tau-protein kinase activity;peptide hormone receptor binding;growth factor receptor binding;disordered domain specific binding