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    FRS3 fibroblast growth factor receptor substrate 3 [ Homo sapiens (human) ]

    Gene ID: 10817, updated on 3-Mar-2026
    Official Symbol
    FRS3provided by HGNC
    Official Full Name
    fibroblast growth factor receptor substrate 3provided by HGNC
    Primary source
    HGNC:HGNC:16970
    See related
    Ensembl:ENSG00000137218 MIM:607744; AllianceGenome:HGNC:16970
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SNT2; FRS2B; SNT-2; FRS2beta; FRS2-beta
    Summary
    This gene encodes a substrate for the fibroblast growth factor receptor. The encoded protein is found in the peripheral plasma membrane and links fibroblast growth factor receptor stimulation to activators of Ras. The encoded protein down-regulates extracellular regulated kinase 2 through direct binding. [provided by RefSeq, Jul 2013]
    Expression
    Broad expression in testis (RPKM 6.0), brain (RPKM 2.3) and 23 other tissues See more
    Orthologs
    all
    Try the new Gene page
    Try the new Transcripts and proteins table
    See FRS3 in Genome Data Viewer
    Location:
    6p21.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (41770176..41779900, complement)
    RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (41598738..41608458, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (41737914..41747638, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene transcription factor EB Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17188 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17189 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17190 Neighboring gene microRNA 10398 Neighboring gene progastricsin Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41735161-41736013 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17191 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17192 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17194 Neighboring gene prickle planar cell polarity protein 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:41755120-41756119 Neighboring gene translocase of outer mitochondrial membrane 6

    Go to nucleotide: Graphics FASTA GenBank

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Related articles in PubMed

    1. Unique role of SNT-2/FRS2beta/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways. Huang L, et al. Oncogene, 2006 Oct 19. PMID 16702953
    2. FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding. Iejima D, et al. Oncogene, 2010 May 27. PMID 20228838
    3. Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras. Wang JK, et al. Oncogene, 1996 Aug 15. PMID 8761293
    4. FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors. Yan KS, et al. J Biol Chem, 2002 May 10. PMID 11877385
    5. The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. Ranzi V, et al. Endocrinology, 2003 Mar. PMID 12586769

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Mechanisms by which FRS2beta acts as a feedback inhibitor of EGFR family members and suggest a role for FRS2beta as a tumor suppressor.
      Title: FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding.
    2. an FRS2beta-CIN85/CD2AP-Cbl axis for downregulation of ErbB2 may regulate ErbB2 protein levels in physiological and pathological settings
      Title: Adaptor protein complex of FRS2β and CIN85/CD2AP provides a novel mechanism for ErbB2/HER2 protein downregulation.
    3. Observational study of gene-disease association. (HuGE Navigator)
      Title: Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.
    4. SNT-2 negatively regulates ERK2 signaling activated via EGF stimulation through direct binding to ERK2
      Title: SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation.
    5. FRS2beta can compensate for the loss of FRS2alpha for activation of MAP kinase when expressed in fibroblasts
      Title: FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts.
    6. Novel mechanism of negative control of EGFR tyrosine kinase activity with SNT-2 by recruiting ERK2.
      Title: Unique role of SNT-2/FRS2beta/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways.
    7. FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors
      Title: FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors.
    Submit: New GeneRIF Correction

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
    EBI GWAS Catalog

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC17167

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables fibroblast growth factor receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables fibroblast growth factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables fibroblast growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane receptor protein tyrosine kinase adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in fibroblast growth factor receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fibroblast growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within fibroblast growth factor receptor signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in fibroblast growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    Preferred Names
    fibroblast growth factor receptor substrate 3
    Names
    FGFR substrate 3
    FGFR-signaling adaptor SNT2
    suc1-associated neurotrophic factor target 2 (FGFR signalling adaptor)
    testicular tissue protein Li 71

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_006653.5 → NP_006644.1  fibroblast growth factor receptor substrate 3

      See identical proteins and their annotated locations for NP_006644.1

      Status: REVIEWED

      Source sequence(s)
      AF036718, HY036161
      Consensus CDS
      CCDS4860.1
      UniProtKB/Swiss-Prot
      O43559, Q5T3D5
      UniProtKB/TrEMBL
      A0A140VJJ7
      Related
      ENSP00000362109.3, ENST00000373018.7
      Conserved Domains (1) summary
      cd01202
      Location:15 → 106
      PTB_FRS2; Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      41770176..41779900 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047418097.1 → XP_047274053.1  fibroblast growth factor receptor substrate 3 isoform X1

      UniProtKB/Swiss-Prot
      O43559, Q5T3D5
      UniProtKB/TrEMBL
      A0A140VJJ7
      Related
      ENSP00000627973.1, ENST00000957914.1

    2. XM_011514254.2 → XP_011512556.1  fibroblast growth factor receptor substrate 3 isoform X1

      See identical proteins and their annotated locations for XP_011512556.1

      UniProtKB/Swiss-Prot
      O43559, Q5T3D5
      UniProtKB/TrEMBL
      A0A140VJJ7
      Related
      ENSP00000600771.1, ENST00000930712.1
      Conserved Domains (1) summary
      cd01202
      Location:15 → 106
      PTB_FRS2; Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      41598738..41608458 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054354066.1 → XP_054210041.1  fibroblast growth factor receptor substrate 3 isoform X1

      UniProtKB/Swiss-Prot
      O43559, Q5T3D5
      UniProtKB/TrEMBL
      A0A140VJJ7

    2. XM_054354067.1 → XP_054210042.1  fibroblast growth factor receptor substrate 3 isoform X1

      UniProtKB/Swiss-Prot
      O43559, Q5T3D5
      UniProtKB/TrEMBL
      A0A140VJJ7
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43559.3 GenPept UniProtKB/Swiss-Prot:O43559

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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