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

Gene ID: 26235, updated on 5-Mar-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (98868535..98947946, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (100042904..100122314, complement)
105.20220307 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
  • 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 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors. Nguyen-Dien GT, et al. EMBO J, 2023 Jul 3. PMID 37161784, Free PMC Article
  2. Novel homozygous mutation in the FBXL4 gene is associated with mitochondria DNA depletion syndrome-13. Wang S, et al. J Neurol Sci, 2020 Sep 15. PMID 32559514
  3. Characterization of the C584R variant in the mtDNA depletion syndrome gene FBXL4, reveals a novel role for FBXL4 as a regulator of mitochondrial fusion. Sabouny R, et al. Biochim Biophys Acta Mol Basis Dis, 2019 Nov 1. PMID 31442532
  4. Molecular and clinical spectra of FBXL4 deficiency. El-Hattab AW, et al. Hum Mutat, 2017 Dec. PMID 28940506
  5. Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer. Stankiewicz E, et al. Sci Rep, 2017 Jul 11. PMID 28698647, Free PMC Article

See all (41) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels.
    Title: FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels.
  4. FBXL4 deficiency increases mitochondrial removal by autophagy.
    Title: FBXL4 deficiency increases mitochondrial removal by autophagy.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis
    Title: FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.
  10. On clinical indication of mitochondrial encephalomyopathy, sequencing of FBXL4 should be performed, even when the activity levels of the MRC enzymes are normal
    Title: A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13.
Submit: New GeneRIF Correction See all GeneRIFs (14)

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 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_2023_10

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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