GeneBe

LYN

protein-coding

LYN proto-oncogene, Src family tyrosine kinase, the group of Src family tyrosine kinases|SH2 domain containing

Gene summary

This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

MANE transcript

NM_002350.4

Inheritance

AD

ClinVar variants

P:4U:124B:102

Top phenotype

Autoinflammatory disease, systemic, with vasculitis

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr8:55,879,835-56,014,169

External References & Databases

Ensembl (ENSG00000254087)NCBI Gene (4067)OMIM (165120)HGNC:6735GenCCUniProt (P07948)AlphaFoldClinVar (LYN)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~134.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autoinflammatory disease, systemic, with vasculitisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957271

Submitter: Labcorp Genetics (formerly Invitae)

autoinflammatory disease, systemic, with vasculitisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0957271

Submitter: Ambry Genetics

autoinflammatory disease, systemic, with vasculitisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957271

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Autoinflammatory disease, systemic, with vasculitisAD

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Refs: 36122175; 36932076Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LYN variants in ClinVar

6 Conditions Cataloged
not providedTotal: 284
Inborn genetic diseasesTotal: 21
Autoinflammatory disease, systemic, with vasculitisTotal: 7
LYN-related disorderTotal: 4
LYN kinase associated vasculopathy and liver fibrosis syndromeTotal: 3
not specifiedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002350.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
95
clinvar
5
clinvar
 102
missense
2
clinvar
113
clinvar
2
clinvar
 117
nonsense
2
clinvar
 2
start loss
1
clinvar
 1
frameshift
3
clinvar
 3
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total40124975230
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002350.4RefSeqNP_002341.112MANE Select
ENST00000519728.6EnsemblENSP00000428924.112MANE Select
NM_001111097.3RefSeqNP_001104567.112Standard
ENST00000520050.1EnsemblENSP00000428313.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
lynDanio rerio

Structure: blood island

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • B cell homeostasis
  • regulation of cytokine production
  • regulation of protein phosphorylation
  • negative regulation of protein phosphorylation
  • positive regulation of protein phosphorylation

Molecular Function

  • protein tyrosine kinase activity
  • non-membrane spanning protein tyrosine kinase activity
  • signaling receptor binding
  • platelet-derived growth factor receptor binding
  • integrin binding

Cellular Component

  • nucleus
  • cytoplasm
  • mitochondrial intermembrane space
  • Golgi apparatus
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000519728
Coding exons
12
Length
131569
Individuals with no LoFs
125740
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125744
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.341262840.4430.00001483392
Missense (PolyPhen)28128.850.21731544
Synonymous-1.161231081.140.00000637922
Loss of Function4.60228.50.07020.00000139351

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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.;

Recessive Scores

pRec
0.172

Intolerance Scores

LoFtool
0.0266
RVIS EVS
-0.69
RVIS percentile EVS
14.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.993

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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