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    FBXL4 F-box and leucine rich repeat protein 4 [ Homo sapiens (human) ]

    Gene ID: 26235, updated on 2-Nov-2024

    Summary

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    Official Symbol
    FBXL4provided by HGNC
    Official Full Name
    F-box and leucine rich repeat protein 4provided by HGNC
    Primary source
    HGNC:HGNC:13601
    See related
    Ensembl:ENSG00000112234 MIM:605654; AllianceGenome:HGNC:13601
    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
    FBL4; FBL5; MTDPS13
    Summary
    This gene encodes a member of the F-box protein family, which are characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one subunit of modular E3 ubiquitin ligase complexes, called SCF complexes, which function in phosphorylation-dependent ubiquitination. The F-box domain mediates protein-protein interactions and binds directly to S-phase kinase-associated protein 1. In addition to an F-box domain, the encoded protein contains at least 9 tandem leucine-rich repeats. The ubiquitin ligase complex containing the encoded protein may function in cell-cycle control by regulating levels of lysine-specific demethylase 4A. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
    Expression
    Ubiquitous expression in thyroid (RPKM 4.4), kidney (RPKM 3.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FBXL4 in Genome Data Viewer
    Location:
    6q16.1-q16.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (98868535..98947946, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (100042904..100122314, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (99316411..99395822, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17411 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24850 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:99283167-99283763 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:99283764-99284359 Neighboring gene uncharacterized LOC124901364 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24851 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17412 Neighboring gene POU class 3 homeobox 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24852 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17413 Neighboring gene Sharpr-MPRA regulatory region 5946 Neighboring gene microRNA 548ai Neighboring gene 3-hydroxybutyrate dehydrogenase 2, pseudogene 1

    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. FBXL4: safeguarding against mitochondrial depletion through suppression of mitophagy. Kulkarni P, et al. Autophagy, 2024 Jun. PMID 38423516, Free PMC Article
    2. Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. Bonnen PE, et al. Am J Hum Genet, 2013 Sep 5. PMID 23993193, Free PMC Article
    3. Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations. Huemer M, et al. J Inherit Metab Dis, 2015 Sep. PMID 25868664, Free PMC Article
    4. A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13. Barøy T, et al. Eur J Med Genet, 2016 Jun. PMID 27182039
    5. FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome. Dai H, et al. Clin Genet, 2017 Apr. PMID 27743463

    See all (48) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. FBXL4: safeguarding against mitochondrial depletion through suppression of mitophagy.
      Title: FBXL4: safeguarding against mitochondrial depletion through suppression of mitophagy.
    2. PPTC7 antagonizes mitophagy by promoting BNIP3 and NIX degradation via SCF[FBXL4].
      Title: PPTC7 antagonizes mitophagy by promoting BNIP3 and NIX degradation via SCF(FBXL4).
    3. Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome.
      Title: Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome.
    4. FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors.
      Title: FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors.
    5. FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels.
      Title: FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels.
    6. FBXL4 deficiency increases mitochondrial removal by autophagy.
      Title: FBXL4 deficiency increases mitochondrial removal by autophagy.
    7. Novel homozygous mutation in the FBXL4 gene is associated with mitochondria DNA depletion syndrome-13.
      Title: Novel homozygous mutation in the FBXL4 gene is associated with mitochondria DNA depletion syndrome-13.
    8. FBXL4 protein promotes mitochondrial fusion. The C584R FBXL4 variant cannot promote mitochondrial fusion.
      Title: Characterization of the C584R variant in the mtDNA depletion syndrome gene FBXL4, reveals a novel role for FBXL4 as a regulator of mitochondrial fusion.
    9. Study found a common genomic copy number loss at 6q16.1-16.2, containing the FBXL4 gene in prostate cancer bone metastases. Loss of FBXL4 was also detected in primary tumors and it was highly associated with prognostic factors including high Gleason score, PSA, as well as poor patient survival, suggesting that FBXL4 loss contributes to prostate cancer progression.
      Title: Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer.
    10. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease.
      Title: Molecular and clinical spectra of FBXL4 deficiency.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    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

    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

    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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within autophagy of mitochondrion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of SCF ubiquitin ligase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial intermembrane space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    part_of ubiquitin ligase complex TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    F-box/LRR-repeat protein 4

    NCBI Reference Sequences (RefSeq)

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    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_033903.2 RefSeqGene

      Range
      5000..84411
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001278716.2 → NP_001265645.1  F-box/LRR-repeat protein 4

      See identical proteins and their annotated locations for NP_001265645.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AL022395, BC091484, DA391493, DA782779
      Consensus CDS
      CCDS5041.1
      UniProtKB/Swiss-Prot
      B2R7Q5, E1P530, O95919, Q5BJH0, Q9UJU0, Q9UKA2
      Related
      ENSP00000358247.1, ENST00000369244.7
      Conserved Domains (3) summary
      sd00034
      Location:403 → 427
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:280 → 318
      F-box-like; F-box-like
      cl28166
      Location:394 → 601
      AMN1; Antagonist of mitotic exit network protein 1

    2. NM_012160.5 → NP_036292.2  F-box/LRR-repeat protein 4

      See identical proteins and their annotated locations for NP_036292.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the functional protein. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AL022395, BC055010, DA391493, DA782779
      Consensus CDS
      CCDS5041.1
      UniProtKB/Swiss-Prot
      B2R7Q5, E1P530, O95919, Q5BJH0, Q9UJU0, Q9UKA2
      Related
      ENSP00000229971.1, ENST00000229971.2
      Conserved Domains (3) summary
      sd00034
      Location:403 → 427
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:280 → 318
      F-box-like; F-box-like
      cl28166
      Location:394 → 601
      AMN1; Antagonist of mitotic exit network protein 1

    RNA

    1. NR_103836.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an internal exon, 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)
      AL022395, BC039819, DA391493, DA782779

    2. NR_103837.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks several exons, and uses an alternate 3'-terminal exon, 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)
      AL022395, BC039819, DA391493, DA782779

    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
      98868535..98947946 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010727.3 → XP_016866216.1  F-box/LRR-repeat protein 4 isoform X2

      Conserved Domains (3) summary
      cd09293
      Location:394 → 577
      AMN1; Antagonist of mitotic exit network protein 1
      sd00034
      Location:377 → 402
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:280 → 326
      F-box-like; F-box-like

    2. XM_047418626.1 → XP_047274582.1  F-box/LRR-repeat protein 4 isoform X2

    3. XM_017010726.2 → XP_016866215.1  F-box/LRR-repeat protein 4 isoform X1

      UniProtKB/Swiss-Prot
      B2R7Q5, E1P530, O95919, Q5BJH0, Q9UJU0, Q9UKA2
      Conserved Domains (3) summary
      sd00034
      Location:403 → 427
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:280 → 318
      F-box-like; F-box-like
      cl28166
      Location:394 → 601
      AMN1; Antagonist of mitotic exit network protein 1

    4. XM_005266930.4 → XP_005266987.1  F-box/LRR-repeat protein 4 isoform X2

      Conserved Domains (3) summary
      cd09293
      Location:394 → 577
      AMN1; Antagonist of mitotic exit network protein 1
      sd00034
      Location:377 → 402
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:280 → 326
      F-box-like; F-box-like

    5. XM_047418625.1 → XP_047274581.1  F-box/LRR-repeat protein 4 isoform X1

      UniProtKB/Swiss-Prot
      B2R7Q5, E1P530, O95919, Q5BJH0, Q9UJU0, Q9UKA2

    6. XM_047418628.1 → XP_047274584.1  F-box/LRR-repeat protein 4 isoform X4

    7. XM_047418627.1 → XP_047274583.1  F-box/LRR-repeat protein 4 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      100042904..100122314 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355138.1 → XP_054211113.1  F-box/LRR-repeat protein 4 isoform X2

    2. XM_054355139.1 → XP_054211114.1  F-box/LRR-repeat protein 4 isoform X2

    3. XM_054355135.1 → XP_054211110.1  F-box/LRR-repeat protein 4 isoform X1

      UniProtKB/Swiss-Prot
      B2R7Q5, E1P530, O95919, Q5BJH0, Q9UJU0, Q9UKA2

    4. XM_054355137.1 → XP_054211112.1  F-box/LRR-repeat protein 4 isoform X2

    5. XM_054355136.1 → XP_054211111.1  F-box/LRR-repeat protein 4 isoform X1

      UniProtKB/Swiss-Prot
      B2R7Q5, E1P530, O95919, Q5BJH0, Q9UJU0, Q9UKA2

    6. XM_054355141.1 → XP_054211116.1  F-box/LRR-repeat protein 4 isoform X4

    7. XM_054355140.1 → XP_054211115.1  F-box/LRR-repeat protein 4 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UKA2.2 GenPept UniProtKB/Swiss-Prot:Q9UKA2

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