GeneBe

FYN

protein-coding

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

Gene summary

This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002037.5

Inheritance

—

ClinVar variants

P:3U:35B:6

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr6:111,660,332-111,873,452

External References & Databases

Ensembl (ENSG00000010810)NCBI Gene (2534)OMIM (137025)HGNC:4037GenCCUniProt (P06241)AlphaFoldClinVar (FYN)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~213.1 kb
Loading mutation effect viewer...

GenCC 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 FYN variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 18
not providedTotal: 14
EBV-positive nodal T- and NK-cell lymphomaTotal: 3
Premature ovarian failureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002037.5. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
2
clinvar
2
clinvar
 9
missense
3
clinvar
21
clinvar
1
clinvar
1
clinvar
 26
nonsense
3
clinvar
 3
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
6
clinvar
 6
Total30353344
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 156 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002037.5RefSeqNP_002028.111MANE Select
ENST00000354650.7EnsemblENSP00000346671.311MANE Select
NM_001370529.1RefSeqNP_001357458.111Standard
NM_153047.4RefSeqNP_694592.111Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • MAPK cascade
  • response to singlet oxygen
  • neuron migration
  • stimulatory C-type lectin receptor signaling pathway
  • adaptive immune response

Molecular Function

  • protein tyrosine kinase activity
  • non-membrane spanning protein tyrosine kinase activity
  • Ras guanyl-nucleotide exchange factor activity
  • signaling receptor binding
  • protein binding

Cellular Component

  • nucleus
  • mitochondrion
  • endosome
  • cytosol
  • actin filament

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000354650
Coding exons
11
Length
213121
Individuals with no LoFs
125740
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125748
p
0.0000318
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense4.031143160.3610.00001793495
Missense (PolyPhen)46177.080.259771947
Synonymous0.1121201220.9870.000007201037
Loss of Function4.67432.90.1220.00000195350

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000350.000035rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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}.;

Recessive Scores

pRec
0.838

Intolerance Scores

LoFtool
0.167
RVIS EVS
-0.54
RVIS percentile EVS
20.54

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.997

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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