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FBXO21 F-box protein 21 [ Homo sapiens (human) ]

Gene ID: 23014, updated on 4-Feb-2026
Official Symbol
FBXO21provided by HGNC
Official Full Name
F-box protein 21provided by HGNC
Primary source
HGNC:HGNC:13592
See related
Ensembl:ENSG00000135108 MIM:609095; AllianceGenome:HGNC:13592
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
FBX21
Summary
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 31.4), ovary (RPKM 26.9) and 25 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See FBXO21 in Genome Data Viewer
Location:
12q24.22
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (117141991..117190470, complement)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (117123006..117171512, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (117579796..117628275, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117477181-117478126 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117478127-117479070 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117479989-117480493 Neighboring gene Sharpr-MPRA regulatory region 12461 Neighboring gene Sharpr-MPRA regulatory region 12935 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117490883-117491488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117492095-117492700 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117500995-117501771 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117500218-117500994 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4910 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4911 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117537215-117537353 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117538220-117538437 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117540353-117540852 Neighboring gene uncharacterized LOC105370010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117556298-117556892 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:117580597-117581796 Neighboring gene tescalcin Neighboring gene TESC antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4913 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7104 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4916 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4917 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117645205-117645705 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117657550-117658106 Neighboring gene MPRA-validated peak1985 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117670646-117670812 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674186-117674690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674691-117675195 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:117718941-117719440 Neighboring gene nitric oxide synthase 1 Neighboring gene elongin C pseudogene 32 Neighboring gene NOS1 1f and 1g alternate promoter region Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117826376-117826876 Neighboring gene NOS1 1c alternate promoter Neighboring gene uncharacterized LOC105370012 Neighboring gene kinase suppressor of ras 2

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. circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis. Jia Z, et al. Kaohsiung J Med Sci, 2022 Dec. PMID 36278814, Free PMC Article
  2. Targeting the KRT16-vimentin axis for metastasis in lung cancer. Wang W, et al. Pharmacol Res, 2023 Jul. PMID 37315823
  3. FBXO21 mediated degradation of p85α regulates proliferation and survival of acute myeloid leukemia. Dobish KK, et al. Leukemia, 2023 Nov. PMID 37689825, Free PMC Article
  4. CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination. Ravindranath AK, et al. Oncotarget, 2015 Sep 22. PMID 26299618, Free PMC Article
  5. FBXO21 mediates the ubiquitylation and proteasomal degradation of EID1. Watanabe K, et al. Genes Cells, 2015 Aug. PMID 26085330

See all (58) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. FBXO21 mediated degradation of p85alpha regulates proliferation and survival of acute myeloid leukemia.
    Title: FBXO21 mediated degradation of p85α regulates proliferation and survival of acute myeloid leukemia.
  2. circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis.
    Title: circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis.
  3. JUNB-FBXO21-ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy.
    Title: JUNB-FBXO21-ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy.
  4. Ser291-phosphorylated form of the multifunctional protein and stem cell marker, CD44, inhibits FBXO21-directed degradation of P-gp.
    Title: CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination.
  5. SCF(FBXO21) polyubiquitylates EID1 both in vitro and in vivo and is required for the efficient degradation of EID1 in both cycling and quiescent cells.
    Title: Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21.
  6. The results suggest that EID1 is a bona fide substrate of FBXO21 and that the control of EID1 abundance by SCF(FBXO)(21) might affect the transcriptional repression activity of EID1.
    Title: FBXO21 mediates the ubiquitylation and proteasomal degradation of EID1.
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

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Replication interactions

Interaction Pubs
Knockdown of F-box protein 21 (FBXO21) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Go to the HIV-1, Human Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ90233, KIAA0875, MGC26682, DKFZp434G058

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-protein transferase activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of ubiquitin ligase complex NAS
Non-traceable Author Statement
more info
 PubMed 
Preferred Names
F-box only protein 21

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_015002.3 → NP_055817.1  F-box only protein 21 isoform 2

    See identical proteins and their annotated locations for NP_055817.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks a 21 nt fragment within the coding region, and thus encodes a 7 aa shorter isoform than variant 1.
    Source sequence(s)
    AB020682, AC026368, BC034045, BC042333, BI550121
    Consensus CDS
    CCDS44989.1
    UniProtKB/TrEMBL
    Q4G104
    Related
    ENSP00000483508.1, ENST00000622495.5
    Conserved Domains (3) summary
    TIGR02097
    Location:493 → 590
    yccV; hemimethylated DNA binding domain
    smart00256
    Location:33 → 74
    FBOX; A Receptor for Ubiquitination Targets
    pfam13369
    Location:215 → 388
    Transglut_core2; Transglutaminase-like superfamily

  2. NM_033624.3 → NP_296373.1  F-box only protein 21 isoform 1

    See identical proteins and their annotated locations for NP_296373.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) contains an additional 21 nt fragment within the coding region, and thus encodes a 7 aa longer isoform than variant 2.
    Source sequence(s)
    AB020682, AC026368, AL136899, BC034045, BC042333, BI550121
    Consensus CDS
    CCDS9184.1
    UniProtKB/Swiss-Prot
    B3KMF0, O94952, Q5BJG0, Q9H087
    UniProtKB/TrEMBL
    Q4G104
    Related
    ENSP00000328187.5, ENST00000330622.9
    Conserved Domains (3) summary
    TIGR02097
    Location:500 → 597
    yccV; hemimethylated DNA binding domain
    smart00256
    Location:33 → 74
    FBOX; A Receptor for Ubiquitination Targets
    pfam13369
    Location:215 → 388
    Transglut_core2; Transglutaminase-like superfamily

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_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    117141991..117190470 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017019038.3 → XP_016874527.1  F-box only protein 21 isoform X2

    UniProtKB/TrEMBL
    H0YIE9
    Related
    ENSP00000449264.1, ENST00000550180.5
    Conserved Domains (3) summary
    TIGR02097
    Location:433 → 530
    yccV; hemimethylated DNA binding domain
    smart00256
    Location:33 → 74
    FBOX; A Receptor for Ubiquitination Targets
    COG2912
    Location:252 → 331
    SirB1; Regulator of sirC expression, contains transglutaminase-like and TPR domains [Signal transduction mechanisms]

  2. XM_017019037.3 → XP_016874526.1  F-box only protein 21 isoform X1

    UniProtKB/TrEMBL
    H0YIE9
    Related
    ENSP00000550295.1, ENST00000880236.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    117123006..117171512 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054371465.1 → XP_054227440.1  F-box only protein 21 isoform X2

    UniProtKB/TrEMBL
    H0YIE9

  2. XM_054371464.1 → XP_054227439.1  F-box only protein 21 isoform X1

    UniProtKB/TrEMBL
    H0YIE9
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O94952.2 GenPept UniProtKB/Swiss-Prot:O94952

Gene LinkOut

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