U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from dbVar

    • Showing Current items.

    AFF2 ALF transcription elongation factor 2 [ Homo sapiens (human) ]

    Gene ID: 2334, updated on 5-Mar-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    AFF2provided by HGNC
    Official Full Name
    ALF transcription elongation factor 2provided by HGNC
    Primary source
    HGNC:HGNC:3776
    See related
    Ensembl:ENSG00000155966 MIM:300806; AllianceGenome:HGNC:3776
    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
    FMR2; MRX2; OX19; FMR2P; FRAXE; XLID109
    Summary
    This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]
    Expression
    Biased expression in placenta (RPKM 3.7), bone marrow (RPKM 2.5) and 8 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    Location:
    Xq28
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (148500617..149000663)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (146765203..147266230)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (147582137..148082193)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene HAX1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30008 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:147507788-147508643 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:147522255-147522928 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:147522929-147523603 Neighboring gene origin of replication in 5' region of AFF2/FMR2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:147582797-147583674 Neighboring gene RPL7L1 pseudogene 11 Neighboring gene MED14-independent group 3 enhancer GRCh37_chrX:147636485-147637684 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30009 Neighboring gene fragile site, folic acid type, rare, fra(X)(q28) E Neighboring gene RN7SK pseudogene 267 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30011 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:148228003-148228504 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:148228505-148229004 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:148264804-148265396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30012 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30013 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30014 Neighboring gene uncharacterized LOC122319696 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:148517664-148518235 Neighboring gene uncharacterized LOC107985667 Neighboring gene Sharpr-MPRA regulatory region 6851

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract. Kuo YJ, et al. Mod Pathol, 2022 Nov. PMID 35701667
    2. Development and validation in 500 female samples of a TP-PCR assay to identify AFF2 GCC expansions. Silva C, et al. Sci Rep, 2021 Jul 19. PMID 34282157, Free PMC Article
    3. Partial AFF2 microduplication in a patient with auditory processing disorder, emotional impairment and macrosomia. da Rocha NB, et al. Am J Med Genet A, 2014 Dec. PMID 25256661
    4. Excess variants in AFF2 detected by massively parallel sequencing of males with autism spectrum disorder. Mondal K, et al. Hum Mol Genet, 2012 Oct 1. PMID 22773736, Free PMC Article
    5. Microdeletion of Xq28 involving the AFF2 (FMR2) gene in two unrelated males with developmental delay. Sahoo T, et al. Am J Med Genet A, 2011 Dec. PMID 22065534

    See all (55) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ALKBH5/YTHDF2-mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation.
      Title: ALKBH5/YTHDF2-mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation.
    2. [AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].
      Title: [AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].
    3. Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract.
      Title: Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract.
    4. Simultaneous Screening of the FRAXA and FRAXE Loci for Rapid Detection of FMR1 CGG and/or AFF2 CCG Repeat Expansions by Triplet-Primed PCR.
      Title: Simultaneous Screening of the FRAXA and FRAXE Loci for Rapid Detection of FMR1 CGG and/or AFF2 CCG Repeat Expansions by Triplet-Primed PCR.
    5. Development and validation in 500 female samples of a TP-PCR assay to identify AFF2 GCC expansions.
      Title: Development and validation in 500 female samples of a TP-PCR assay to identify AFF2 GCC expansions.
    6. DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity.
      Title: DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity.
    7. Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts.
      Title: Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts.
    8. AFF2/FMR2 regulates the transcription and toxicity of expanded G4C2 repeats in human C9ORF72-ALS/FTD neurons.
      Title: Transcription elongation factor AFF2/FMR2 regulates expression of expanded GGGGCC repeat-containing C9ORF72 allele in ALS/FTD.
    9. Partial AFF2 microduplication in a patient with auditory processing disorder, emotional impairment and macrosomia.
      Title: Partial AFF2 microduplication in a patient with auditory processing disorder, emotional impairment and macrosomia.
    10. FMR2 is an upstream regulator of FOS and JUN, and further link deregulation of the immediate early response genes to the pathology of ID- and FRAXE-associated ID in particular.
      Title: Loss of FMR2 further emphasizes the link between deregulation of immediate early response genes FOS and JUN and intellectual disability.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

    Go to the top of the page Help

    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
    FRAXE
    MedGen: C0751157 OMIM: 309548 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-12-08)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-12-08)

    ClinGen Genome Curation PagePubMed

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

    Go to the top of the page Help

    Replication interactions

    Interaction Pubs
    Knockdown of AF4/FMR2 family, member 2 (AFF2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G-quadruplex RNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables G-quadruplex RNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in RNA splicing IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in brain development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in learning or memory IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mRNA processing IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within nuclear speck organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of RNA splicing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of RNA splicing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in nuclear speck IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT part_of super elongation complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    AF4/FMR2 family member 2
    Names
    protein FMR-2

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    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_016313.2 RefSeqGene

      Range
      4999..505045
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001169122.2 → NP_001162593.1  AF4/FMR2 family member 2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has multiple differences, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC002368, AC231841, L76569, U48436
      Consensus CDS
      CCDS78510.1
      UniProtKB/Swiss-Prot
      P51816
      Related
      ENSP00000345459.4, ENST00000342251.7
      Conserved Domains (1) summary
      pfam05110
      Location:19 → 1273
      AF-4; AF-4 proto-oncoprotein

    2. NM_001169123.2 → NP_001162594.1  AF4/FMR2 family member 2 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AC002368, AC231841, BC132683, U48436
      UniProtKB/Swiss-Prot
      P51816
      Conserved Domains (1) summary
      pfam05110
      Location:19 → 1298
      AF-4; AF-4 proto-oncoprotein

    3. NM_001169124.2 → NP_001162595.1  AF4/FMR2 family member 2 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has multiple differences, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AC002368, AC231841, BC143744, U48436
      Consensus CDS
      CCDS76040.1
      UniProtKB/Swiss-Prot
      P51816
      Related
      ENSP00000359486.6, ENST00000370457.9
      Conserved Domains (1) summary
      pfam05110
      Location:19 → 1273
      AF-4; AF-4 proto-oncoprotein

    4. NM_001169125.2 → NP_001162596.1  AF4/FMR2 family member 2 isoform 5

      See identical proteins and their annotated locations for NP_001162596.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has multiple differences, compared to variant 1. The encoded isoform (5) is shorter than isoform 1.
      Source sequence(s)
      AC002368, AC231841, BC143740, U48436
      UniProtKB/Swiss-Prot
      P51816
      Conserved Domains (1) summary
      pfam05110
      Location:19 → 1269
      AF-4; AF-4 proto-oncoprotein

    5. NM_001170628.1 → NP_001164099.1  AF4/FMR2 family member 2 isoform 6

      See identical proteins and their annotated locations for NP_001164099.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) has multiple differences, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (6) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC002368, AC231841, AK301927
      Consensus CDS
      CCDS55521.1
      UniProtKB/Swiss-Prot
      P51816
      Related
      ENSP00000286437.5, ENST00000286437.7
      Conserved Domains (1) summary
      pfam05110
      Location:18 → 949
      AF-4; AF-4 proto-oncoprotein

    6. NM_002025.4 → NP_002016.2  AF4/FMR2 family member 2 isoform 1

      See identical proteins and their annotated locations for NP_002016.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC002368, AC231841, BC132683, BC143744, L76569
      Consensus CDS
      CCDS14684.1
      UniProtKB/Swiss-Prot
      A2RTY4, B4DXD5, B7WNQ1, B7ZLD6, B7ZLD9, O43786, O60215, P51816, P78407, Q13521, Q14323, Q7Z2F7, Q7Z400, Q9UNA5
      Related
      ENSP00000359489.2, ENST00000370460.7
      Conserved Domains (1) summary
      pfam05110
      Location:19 → 1308
      AF-4; AF-4 proto-oncoprotein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      148500617..149000663
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      146765203..147266230
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51816.4 GenPept UniProtKB/Swiss-Prot:P51816

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous