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    IRF4 interferon regulatory factor 4 [ Homo sapiens (human) ]

    Gene ID: 3662, updated on 2-Nov-2024

    Summary

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    Official Symbol
    IRF4provided by HGNC
    Official Full Name
    interferon regulatory factor 4provided by HGNC
    Primary source
    HGNC:HGNC:6119
    See related
    Ensembl:ENSG00000137265 MIM:601900; AllianceGenome:HGNC:6119
    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
    MUM1; LSIRF; SHEP8; NF-EM5
    Summary
    The protein encoded by this gene belongs to the IRF (interferon regulatory factor) family of transcription factors, characterized by an unique tryptophan pentad repeat DNA-binding domain. The IRFs are important in the regulation of interferons in response to infection by virus, and in the regulation of interferon-inducible genes. This family member is lymphocyte specific and negatively regulates Toll-like-receptor (TLR) signaling that is central to the activation of innate and adaptive immune systems. A chromosomal translocation involving this gene and the IgH locus, t(6;14)(p25;q32), may be a cause of multiple myeloma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2010]
    Expression
    Broad expression in lymph node (RPKM 13.5), bone marrow (RPKM 12.6) and 14 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IRF4 in Genome Data Viewer
    Location:
    6p25.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (391752..411443)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (250136..269771)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (391752..411443)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105374870 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23813 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23814 Neighboring gene MPRA-validated peak5614 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr6:281277-281431 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23815 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23816 Neighboring gene H3K27ac hESC enhancers GRCh37_chr6:291666-292166 and GRCh37_chr6:292167-292667 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23818 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:293614-293770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23819 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23820 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23821 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23822 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16803 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16804 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:314342-314521 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23824 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23827 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23826 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23825 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23828 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:324055-324866 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23829 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:329543-330742 Neighboring gene dual specificity phosphatase 22 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23830 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23831 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23832 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16805 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23833 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:342926-343426 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23834 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23835 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:351472-352326 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23836 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23837 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:361141-361640 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23838 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:373619-374192 Neighboring gene MPRA-validated peak5616 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:378942-379888 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23839 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23841 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16806 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16807 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16808 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16813 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16812 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16811 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16810 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16809 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23842 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23843 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23844 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23845 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23846 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23847 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23848 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23852 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23851 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23850 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23849 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:434746-434910 Neighboring gene MPRA-validated peak5617 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16814 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23854 Neighboring gene MPRA-validated peak5618 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr6:517255-517445 Neighboring gene exocyst complex component 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:551909-552730 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:557275-557462 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:563721-564920 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:582671-583870 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23855 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16815 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23856 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:659114-660062 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:660063-661010 Neighboring gene MARK2 pseudogene 18 Neighboring gene HUS1 checkpoint clamp component B

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Comprehensive genomic profiling of IgM multiple myeloma identifies IRF4 as a prognostic marker. Ryu D, et al. Oncotarget, 2016 Jul 26. PMID 27223072, Free PMC Article
    2. Role of IRF4 in IFN-stimulated gene induction and maintenance of Kaposi sarcoma-associated herpesvirus latency in primary effusion lymphoma cells. Forero A, et al. J Immunol, 2013 Aug 1. PMID 23804715, Free PMC Article
    3. Polymorphisms in the IRF-4 gene, asthma and recurrent bronchitis in children. Pinto LA, et al. Clin Exp Allergy, 2013 Oct. PMID 24074333
    4. A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Praetorius C, et al. Cell, 2013 Nov 21. PMID 24267888, Free PMC Article
    5. No evidence for a genetic association of IRF4 with systemic lupus erythematosus in a Chinese population. Liu SS, et al. Z Rheumatol, 2014 Aug. PMID 24292686

    See all (256) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Interferon-induced protein 44 (IFI44) and interferon regulatory factor 4 (IRF4) gene expression in rheumatoid arthritis.
      Title: Interferon-induced protein 44 (IFI44) and interferon regulatory factor 4 (IRF4) gene expression in rheumatoid arthritis.
    2. IRF4 impedes human CD8 T cell function and promotes cell proliferation and PD-1 expression.
      Title: IRF4 impedes human CD8 T cell function and promotes cell proliferation and PD-1 expression.
    3. Clinical boundaries in adult cases of large B cell lymphoma with IRF4 rearrangement.
      Title: Clinical boundaries in adult cases of large B cell lymphoma with IRF4 rearrangement.
    4. Transcriptional reprogramming by mutated IRF4 in lymphoma.
      Title: Transcriptional reprogramming by mutated IRF4 in lymphoma.
    5. Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.
      Title: Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.
    6. Human inborn errors of immunity associated with IRF4.
      Title: Human inborn errors of immunity associated with IRF4.
    7. NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.
      Title: NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.
    8. Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
      Title: Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
    9. MUM-1 in canine lymphoma: A pilot study.
      Title: MUM-1 in canine lymphoma: A pilot study.
    10. Prevalence of IRF4 rearrangement in large B-cell lymphomas of the Waldeyer's ring in adults.
      Title: Prevalence of IRF4 rearrangement in large B-cell lymphomas of the Waldeyer's ring in adults.
    Submit: New GeneRIF Correction See all GeneRIFs (201)

    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Skin/hair/eye pigmentation, variation in, 8
    MedGen: C2673265 OMIM: 611724 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
    EBI GWAS Catalog
    A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.
    EBI GWAS Catalog
    A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia.
    EBI GWAS Catalog
    Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia.
    EBI GWAS Catalog
    Genetic determinants of hair, eye and skin pigmentation in Europeans.
    EBI GWAS Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans.
    EBI GWAS Catalog
    Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
    EBI GWAS Catalog
    Genome-wide association study of serum albumin:globulin ratio in Korean populations.
    EBI GWAS Catalog
    Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.
    EBI GWAS Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    EBI GWAS Catalog
    Web-based, participant-driven studies yield novel genetic associations for common traits.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sequence-specific DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription coactivator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell activation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in T-helper 17 cell lineage commitment ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in defense response to protozoan ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in immune system process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in myeloid dendritic cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of toll-like receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of interleukin-10 production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of interleukin-13 production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of interleukin-2 production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of interleukin-4 production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of T-helper cell differentiation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    part_of nucleosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IC
    Inferred by Curator
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    interferon regulatory factor 4
    Names
    lymphocyte-specific interferon regulatory factor
    multiple myeloma oncogene 1

    NCBI Reference Sequences (RefSeq)

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    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.

    Genomic

    1. NG_027728.1 RefSeqGene

      Range
      5014..24705
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001195286.2 → NP_001182215.1  interferon regulatory factor 4 isoform 2

      See identical proteins and their annotated locations for NP_001182215.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site at an internal coding exon compared to variant 1, resulting in an isoform (2) that is 1 aa shorter than isoform 1.
      Source sequence(s)
      AL512308, AL589962, AW197089, BG230623, BM551611, KF458069, U52682, U63738
      Consensus CDS
      CCDS93847.1
      UniProtKB/TrEMBL
      F2Z3D5
      Related
      ENSP00000512940.1, ENST00000696871.1
      Conserved Domains (2) summary
      pfam00605
      Location:23 → 128
      IRF; Interferon regulatory factor transcription factor
      pfam10401
      Location:249 → 417
      IRF-3; Interferon-regulatory factor 3

    2. NM_002460.4 → NP_002451.2  interferon regulatory factor 4 isoform 1

      See identical proteins and their annotated locations for NP_002451.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AL512308, AL589962, AW197089, BC015752, BG230623, BM551611, KF458069, U52682, U63738
      Consensus CDS
      CCDS4469.1
      UniProtKB/Swiss-Prot
      Q15306, Q5VUI7, Q99660
      UniProtKB/TrEMBL
      F2Z3D5
      Related
      ENSP00000370343.4, ENST00000380956.9
      Conserved Domains (2) summary
      pfam00605
      Location:23 → 128
      IRF; Interferon regulatory factor transcription factor
      pfam10401
      Location:250 → 418
      IRF-3; Interferon-regulatory factor 3

    RNA

    1. NR_046000.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate 3' splice pattern, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL512308, AL589962, AW197089, D78261, KF458069, U52682

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_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
      391752..411443
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006715090.3 → XP_006715153.1  interferon regulatory factor 4 isoform X1

      See identical proteins and their annotated locations for XP_006715153.1

      UniProtKB/TrEMBL
      F2Z3D5
      Conserved Domains (2) summary
      pfam00605
      Location:23 → 128
      IRF; Interferon regulatory factor transcription factor
      pfam10401
      Location:214 → 382
      IRF-3; Interferon-regulatory factor 3

    2. XM_047418730.1 → XP_047274686.1  interferon regulatory factor 4 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      250136..269771
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355349.1 → XP_054211324.1  interferon regulatory factor 4 isoform X1

    2. XM_054355350.1 → XP_054211325.1  interferon regulatory factor 4 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_036585.1: Suppressed sequence

      Description
      NR_036585.1: This RefSeq was permanently suppressed because currently there is support for the transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q15306.1 GenPept UniProtKB/Swiss-Prot:Q15306

    Gene LinkOut

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

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