LYN
LYN proto-oncogene, Src family tyrosine kinase, the group of Src family tyrosine kinases|SH2 domain containing
Basic information
Region (hg38): 8:55879835-56014169
Links
Phenotypes
GenCC
Source:
- autoinflammatory disease, systemic, with vasculitis (Strong), mode of inheritance: AD
- autoinflammatory disease, systemic, with vasculitis (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Autoinflammatory disease, systemic, with vasculitis | AD | Allergy/Immunology/Infectious | The condition can manifest with multiple autoinflammatory-related manifestations, and medical management (eg, with tyrosine kinase inhibitors, anti-IL1 therapy) has been described as beneficial | Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal | 36122175; 36932076 |
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 LYN 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 | 63 | 72 | ||||
| missense | 62 | 62 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 8 | 11 | 19 | |||
| non coding | 45 | 48 | ||||
| Total | 0 | 0 | 67 | 108 | 9 |
Variants in LYN
This is a list of pathogenic ClinVar variants found in the LYN region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-55941869-A-G | Uncertain significance (Aug 06, 2023) | |||
| 8-55941882-G-A | Uncertain significance (Jan 12, 2024) | |||
| 8-55941890-A-G | Uncertain significance (Jun 20, 2022) | |||
| 8-55941895-G-A | Likely benign (Feb 08, 2023) | |||
| 8-55941901-C-T | Likely benign (Mar 27, 2023) | |||
| 8-55941903-A-G | Uncertain significance (Jun 04, 2022) | |||
| 8-55941931-A-G | Uncertain significance (Oct 07, 2022) | |||
| 8-55941933-G-A | Uncertain significance (Mar 13, 2022) | |||
| 8-55941947-A-G | Inborn genetic diseases | Uncertain significance (Nov 18, 2023) | ||
| 8-55941968-A-G | Uncertain significance (Oct 27, 2021) | |||
| 8-55941970-G-A | Likely benign (Oct 03, 2023) | |||
| 8-55941981-A-G | Uncertain significance (Oct 14, 2023) | |||
| 8-55942004-T-A | Likely benign (Aug 08, 2023) | |||
| 8-55942007-CAG-C | Likely benign (Jan 10, 2024) | |||
| 8-55942008-A-G | Likely benign (May 18, 2023) | |||
| 8-55946434-A-T | Likely benign (Jul 14, 2023) | |||
| 8-55946443-C-T | Likely benign (Sep 22, 2023) | |||
| 8-55946444-G-A | Conflicting classifications of pathogenicity (Nov 01, 2022) | |||
| 8-55946448-G-A | Uncertain significance (Sep 23, 2023) | |||
| 8-55946456-A-C | Uncertain significance (Jun 23, 2023) | |||
| 8-55946456-A-G | Likely benign (Sep 06, 2022) | |||
| 8-55946466-T-C | Likely benign (Dec 28, 2023) | |||
| 8-55946468-A-G | Likely benign (Jun 23, 2023) | |||
| 8-55946471-T-A | Likely benign (Aug 15, 2022) | |||
| 8-55946471-T-C | Likely benign (Oct 16, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LYN | protein_coding | protein_coding | ENST00000519728 | 12 | 131569 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00114 | 125740 | 0 | 4 | 125744 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.34 | 126 | 284 | 0.443 | 0.0000148 | 3392 |
| Missense in Polyphen | 28 | 128.85 | 0.2173 | 1544 | ||
| Synonymous | -1.16 | 123 | 108 | 1.14 | 0.00000637 | 922 |
| Loss of Function | 4.60 | 2 | 28.5 | 0.0702 | 0.00000139 | 351 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000545 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000180 | 0.0000176 |
| Middle Eastern | 0.0000545 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down- regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down- regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:7687428}.;
- Disease
- DISEASE: Note=Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.;
- Pathway
- Platelet activation - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Long-term depression - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;IL-5 Signaling Pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;B Cell Receptor Signaling Pathway;IL-3 Signaling Pathway;Kit receptor signaling pathway;Chemokine signaling pathway;Microglia Pathogen Phagocytosis Pathway;Developmental Biology;Signal Transduction;Signaling by Interleukins;Growth hormone receptor signaling;phosphoinositides and their downstream targets;bcr signaling pathway;Cytokine Signaling in Immune system;CD28 co-stimulation;CTLA4 inhibitory signaling;Costimulation by the CD28 family;Dectin-2 family;Signaling by the B Cell Receptor (BCR);C-type lectin receptors (CLRs);EPH-Ephrin signaling;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;EPHA-mediated growth cone collapse;Innate Immune System;Immune System;EPHB-mediated forward signaling;Cyclin D associated events in G1;G1 Phase;EPH-ephrin mediated repulsion of cells;IL5-mediated signaling events;Adaptive Immune System;KitReceptor;Mitotic G1-G1/S phases;CD22 mediated BCR regulation;BCR;Platelet Adhesion to exposed collagen;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Regulation of KIT signaling;fc epsilon receptor i signaling in mast cells;EGFR1;PECAM1 interactions;CXCR4-mediated signaling events;Cell surface interactions at the vascular wall;Hemostasis;BCR signaling pathway;Thromboxane A2 receptor signaling;IL2;IL3;Ephrin B reverse signaling;Class I PI3K signaling events;EPO signaling pathway;Axon guidance;Signaling by SCF-KIT;IL5;FCERI mediated NF-kB activation;Cell Cycle;IL6;Signaling by Receptor Tyrosine Kinases;Cell Cycle, Mitotic;GMCSF-mediated signaling events;LPA receptor mediated events;Glypican 1 network;Fc-epsilon receptor I signaling in mast cells;IL8- and CXCR1-mediated signaling events;Regulation of p38-alpha and p38-beta;Signaling events mediated by Stem cell factor receptor (c-Kit);Alpha-synuclein signaling;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;IL8- and CXCR2-mediated signaling events;EPHA forward signaling;Role of LAT2/NTAL/LAB on calcium mobilization;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- loftool
- 0.0266
- rvis_EVS
- -0.69
- rvis_percentile_EVS
- 14.97
Haploinsufficiency Scores
- pHI
- 0.808
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.623
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
- Lyn
- Phenotype
- 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); digestive/alimentary 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; respiratory system phenotype; liver/biliary system phenotype; homeostasis/metabolism 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);
Zebrafish Information Network
- Gene name
- lyn
- Affected structure
- blood island
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- B cell homeostasis;regulation of cytokine production;regulation of protein phosphorylation;negative regulation of protein phosphorylation;positive regulation of protein phosphorylation;stimulatory C-type lectin receptor signaling pathway;adaptive immune response;Fc receptor mediated stimulatory signaling pathway;tolerance induction to self antigen;histamine secretion by mast cell;platelet degranulation;negative regulation of myeloid leukocyte differentiation;immune response-regulating cell surface receptor signaling pathway;Fc receptor mediated inhibitory signaling pathway;regulation of B cell apoptotic process;protein phosphorylation;cellular response to DNA damage stimulus;response to sterol depletion;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;blood coagulation;positive regulation of cell population proliferation;negative regulation of cell population proliferation;response to toxic substance;response to hormone;response to carbohydrate;positive regulation of neuron projection development;oligodendrocyte development;positive regulation of phosphatidylinositol 3-kinase signaling;response to organic cyclic compound;viral process;peptidyl-tyrosine phosphorylation;cell differentiation;platelet activation;erythrocyte differentiation;positive regulation of cell migration;negative regulation of B cell proliferation;neuron projection development;T cell costimulation;lipopolysaccharide-mediated signaling pathway;cellular response to extracellular stimulus;response to insulin;regulation of mast cell activation;regulation of cell adhesion mediated by integrin;negative regulation of toll-like receptor 2 signaling pathway;negative regulation of toll-like receptor 4 signaling pathway;cellular response to heat;peptidyl-tyrosine autophosphorylation;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;response to drug;positive regulation of tyrosine phosphorylation of STAT protein;response to amino acid;regulation of mast cell degranulation;negative regulation of MAP kinase activity;positive regulation of phosphatidylinositol 3-kinase activity;innate immune response;regulation of erythrocyte differentiation;positive regulation of Ras protein signal transduction;protein autophosphorylation;ephrin receptor signaling pathway;response to axon injury;cytokine secretion;regulation of cytokine secretion;regulation of inflammatory response;negative regulation of immune response;B cell receptor signaling pathway;regulation of B cell receptor signaling pathway;positive regulation of B cell receptor signaling pathway;leukocyte migration;positive regulation of cellular component movement;regulation of release of sequestered calcium ion into cytosol;positive regulation of glial cell proliferation;positive regulation of Fc receptor mediated stimulatory signaling pathway;JAK-STAT cascade involved in growth hormone signaling pathway;positive regulation of stress-activated protein kinase signaling cascade;regulation of ERK1 and ERK2 cascade;negative regulation of ERK1 and ERK2 cascade;positive regulation of oligodendrocyte progenitor proliferation;negative regulation of mast cell proliferation;positive regulation of mast cell proliferation;cellular response to retinoic acid;regulation of monocyte chemotaxis;regulation of platelet aggregation;dendritic cell differentiation;negative regulation of intracellular signal transduction;positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process;positive regulation of dendritic cell apoptotic process
- Cellular component
- nucleus;cytoplasm;mitochondrial intermembrane space;Golgi apparatus;cytosol;plasma membrane;cell-cell adherens junction;postsynaptic density;mitochondrial crista;extrinsic component of cytoplasmic side of plasma membrane;integrin alpha2-beta1 complex;mast cell granule;intracellular membrane-bounded organelle;membrane raft;perinuclear region of cytoplasm;extracellular exosome;glutamatergic synapse;postsynaptic specialization, intracellular component
- Molecular function
- protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;signaling receptor binding;platelet-derived growth factor receptor binding;integrin binding;protein binding;ATP binding;kinase activity;SH3 domain binding;ubiquitin protein ligase binding;gamma-tubulin binding;glycosphingolipid binding;ion channel binding;ephrin receptor binding;phosphoprotein binding;phosphorylation-dependent protein binding