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 k... See more...

Aliases for FBXL4 Gene

Aliases for FBXL4 Gene

  • F-Box And Leucine Rich Repeat Protein 4 2 3 5
  • F-Box/LRR-Repeat Protein 4 3 4
  • FBL4 3 4
  • FBL5 3 4
  • F-Box And Leucine-Rich Repeat Protein 4 4
  • F-Box Protein FBL4/FBL5 4
  • MTDPS13 3

External Ids for FBXL4 Gene

Previous GeneCards Identifiers for FBXL4 Gene

  • GC06M099190
  • GC06M099338
  • GC06M099367
  • GC06M099428
  • GC06M096760
  • GC06M099316

Summaries for FBXL4 Gene

Entrez Gene Summary for FBXL4 Gene

  • 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]

GeneCards Summary for FBXL4 Gene

FBXL4 (F-Box And Leucine Rich Repeat Protein 4) is a Protein Coding gene. Diseases associated with FBXL4 include Mitochondrial Dna Depletion Syndrome 13 and Mitochondrial Dna Depletion Syndrome. Among its related pathways are Class I MHC mediated antigen processing and presentation and Innate Immune System. An important paralog of this gene is FBXL2.

Additional gene information for FBXL4 Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FBXL4 Gene

Genomics for FBXL4 Gene

GeneHancer (GH) Regulatory Elements for FBXL4 Gene

Promoters and enhancers for FBXL4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J098945 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 505.4 +0.7 741 3.1 FOXK2 ZBTB40 EP300 MYC POLR2G PHF8 ZFX ZIC2 POLR2A ZBTB10 FBXL4 lnc-FBXL4-1 piR-57135-049
GH06J099566 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 28.4 -620.0 -619994 3.2 RXRA ZBTB40 ZNF217 EP300 TCF12 POLR2G SP1 GTF2E2 PHF8 SIX5 CCNC NONHSAG044439.2 lnc-USP45-3 ENSG00000228506 PNISR ENSG00000219755 USP45 FBXL4 HE855958 TSTD3
GH06J098831 Promoter/Enhancer 2.1 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 4.6 +112.1 112105 9 ZNF217 CTCF FOS ZNF639 ZNF10 ZIC2 ZBTB10 ZNF263 ZNF623 AFF1 POU3F2 BDH2P1 FBXL4 ENSG00000283010 HSALNG0052162
GH06J098039 Enhancer 1.7 VISTA UCNEbase Ensembl ENCODE dbSUPER 5.2 +904.7 904705 10.2 EP300 CTCF TEAD4 ZIC2 HDAC2 ZNF316 SMC3 MAFF GATA3 MXI1 FBXL4 MIR2113 RF00994-932 ENSG00000271860
GH06J098976 Enhancer 0.9 VISTA UCNEbase 5.2 -29.9 -29904 2.1 EP300 IRF1 NR3C1 NFE2 ZFP91 POLR2A HLF GATA1 SOX13 FBXL4 HSALNG0052170 lnc-FBXL4-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FBXL4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FBXL4

Top Transcription factor binding sites by QIAGEN in the FBXL4 gene promoter:
  • CUTL1
  • Elk-1
  • FOXO3
  • Gfi-1
  • Lmo2
  • Pax-3
  • POU2F1
  • POU2F1a
  • S8

Genomic Locations for FBXL4 Gene

Genomic Locations for FBXL4 Gene
chr6:98,868,535-98,948,006
(GRCh38/hg38)
Size:
79,472 bases
Orientation:
Minus strand
chr6:99,316,420-99,395,849
(GRCh37/hg19)
Size:
79,430 bases
Orientation:
Minus strand

Genomic View for FBXL4 Gene

Genes around FBXL4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FBXL4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FBXL4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FBXL4 Gene

Proteins for FBXL4 Gene

  • Protein details for FBXL4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UKA2-FBXL4_HUMAN
    Recommended name:
    F-box/LRR-repeat protein 4
    Protein Accession:
    Q9UKA2
    Secondary Accessions:
    • B2R7Q5
    • E1P530
    • O95919
    • Q5BJH0
    • Q9UJU0

    Protein attributes for FBXL4 Gene

    Size:
    621 amino acids
    Molecular mass:
    70097 Da
    Quaternary structure:
    • Part of a SCF (SKP1-cullin-F-box) protein ligase complex.

neXtProt entry for FBXL4 Gene

Post-translational modifications for FBXL4 Gene

  • Ubiquitination at Lys115 and Lys537
  • Modification sites at PhosphoSitePlus

Other Protein References for FBXL4 Gene

No data available for DME Specific Peptides for FBXL4 Gene

Domains & Families for FBXL4 Gene

Gene Families for FBXL4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for FBXL4 Gene

Blocks:
  • Leucine-rich repeat signature
  • Leucine-rich repeat, cysteine-containing subtype
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FBXL4 Gene

GenScript: Design optimal peptide antigens:
  • F-box protein FBL4/FBL5 (FBXL4_HUMAN)
genes like me logo Genes that share domains with FBXL4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for FBXL4 Gene

Function for FBXL4 Gene

Phenotypes From GWAS Catalog for FBXL4 Gene

Gene Ontology (GO) - Molecular Function for FBXL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 contributes_to ubiquitin-protein transferase activity IBA 21873635
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with FBXL4: view
genes like me logo Genes that share phenotypes with FBXL4: view

Human Phenotype Ontology for FBXL4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Clone Products

No data available for Molecular function , Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for FBXL4 Gene

Localization for FBXL4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FBXL4 Gene

Cytoplasm. Nucleus. Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FBXL4 gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 4
plasma membrane 1
cytoskeleton 1
extracellular 0
lysosome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear speckles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FBXL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000151 ubiquitin ligase complex TAS 10531035
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005739 mitochondrion IEA --
GO:0005758 mitochondrial intermembrane space IDA 23993194
genes like me logo Genes that share ontologies with FBXL4: view

Pathways & Interactions for FBXL4 Gene

genes like me logo Genes that share pathways with FBXL4: view

Gene Ontology (GO) - Biological Process for FBXL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination TAS --
GO:0006511 ubiquitin-dependent protein catabolic process TAS,IBA 21873635
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA 21873635
GO:0043687 post-translational protein modification TAS --
genes like me logo Genes that share ontologies with FBXL4: view

No data available for SIGNOR curated interactions for FBXL4 Gene

Drugs & Compounds for FBXL4 Gene

No Compound Related Data Available

Transcripts for FBXL4 Gene

mRNA/cDNA for FBXL4 Gene

2 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for FBXL4 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10
SP1:
SP2: -

Relevant External Links for FBXL4 Gene

GeneLoc Exon Structure for
FBXL4

Expression for FBXL4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FBXL4 Gene

Protein differential expression in normal tissues from HIPED for FBXL4 Gene

This gene is overexpressed in Serum (68.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FBXL4 Gene



Protein tissue co-expression partners for FBXL4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FBXL4

SOURCE GeneReport for Unigene cluster for FBXL4 Gene:

Hs.536850

mRNA Expression by UniProt/SwissProt for FBXL4 Gene:

Q9UKA2-FBXL4_HUMAN
Tissue specificity: Expressed in heart, kidney, liver, lung, pancreas, and placenta, but not in skeletal muscle.

Evidence on tissue expression from TISSUES for FBXL4 Gene

  • Nervous system(4.4)
  • Eye(4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FBXL4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cheek
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • outer ear
  • pharynx
  • skull
Thorax:
  • esophagus
Abdomen:
  • stomach
Pelvis:
  • penis
  • urethra
General:
  • hair
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with FBXL4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for FBXL4 Gene

Orthologs for FBXL4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for FBXL4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FBXL4 31 30
  • 99.14 (n)
OneToOne
dog
(Canis familiaris)
Mammalia FBXL4 31 30
  • 93.13 (n)
OneToOne
cow
(Bos Taurus)
Mammalia FBXL4 31 30
  • 91.04 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Fbxl4 30
  • 89.39 (n)
oppossum
(Monodelphis domestica)
Mammalia FBXL4 31
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Fbxl4 17 31 30
  • 88.46 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia FBXL4 31
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves FBXL4 31 30
  • 81.29 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia FBXL4 31
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100490265 30
  • 72.44 (n)
zebrafish
(Danio rerio)
Actinopterygii fbxl4 31 30
  • 64.9 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Fbxl4 31 30
  • 44.22 (n)
OneToOne
CG1839 32
  • 31 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000471 30
  • 39.79 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GRR1 31
  • 10 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3673 31
  • 37 (a)
OneToOne
Species where no ortholog for FBXL4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for FBXL4 Gene

ENSEMBL:
Gene Tree for FBXL4 (if available)
TreeFam:
Gene Tree for FBXL4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FBXL4: view image

Paralogs for FBXL4 Gene

genes like me logo Genes that share paralogs with FBXL4: view

Variants for FBXL4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FBXL4 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
666968 Likely Pathogenic: Mitochondrial DNA depletion syndrome 98,905,517(-) C/A NONSENSE,NON_CODING_TRANSCRIPT_VARIANT
675564 Likely Benign: not provided 98,927,711(-) T/C NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
676917 Likely Benign: not provided 98,905,397(-) A/G INTRON_VARIANT
680582 Benign: not provided 98,926,304(-) A/C INTRON_VARIANT
680583 Benign: not provided 98,926,179(-) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for FBXL4 Gene

Structural Variations from Database of Genomic Variants (DGV) for FBXL4 Gene

Variant ID Type Subtype PubMed ID
esv26393 CNV loss 19812545
esv2659264 CNV deletion 23128226
esv2732468 CNV deletion 23290073
esv3610113 CNV loss 21293372
esv3610114 CNV loss 21293372
nsv1029536 CNV loss 25217958
nsv474745 CNV novel sequence insertion 20440878
nsv604253 CNV gain 21841781
nsv823788 CNV loss 20364138

Variation tolerance for FBXL4 Gene

Residual Variation Intolerance Score: 20.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.58; 44.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FBXL4 Gene

Human Gene Mutation Database (HGMD)
FBXL4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FBXL4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FBXL4 Gene

Disorders for FBXL4 Gene

MalaCards: The human disease database

(9) MalaCards diseases for FBXL4 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
mitochondrial dna depletion syndrome 13
  • mtdps13
mitochondrial dna depletion syndrome
  • mtdna depletion syndrome
mitochondrial encephalomyopathy
  • mitochondrial encephalomyopathies
cerebellar ataxia, nonprogressive, with mental retardation
  • canpmr
mitochondrial dna maintenance defects
  • mitochondrial dna maintenance syndrome
- elite association - COSMIC cancer census association via MalaCards
Search FBXL4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FBXL4_HUMAN
  • Mitochondrial DNA depletion syndrome 13 (MTDPS13) [MIM:615471]: An autosomal recessive disorder characterized by early infantile onset of encephalopathy, hypotonia, lactic acidosis, and severe global developmental delay. Cells derived from patient tissues show defects in mitochondrial oxidative phosphorylation and decreased mtDNA content. {ECO:0000269 PubMed:23993193, ECO:0000269 PubMed:23993194, ECO:0000269 PubMed:27182039}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for FBXL4

genes like me logo Genes that share disorders with FBXL4: view

No data available for Genatlas for FBXL4 Gene

Publications for FBXL4 Gene

  1. Identification of a family of human F-box proteins. (PMID: 10531035) Cenciarelli C … Pagano M (Current biology : CB 1999) 2 3 4 54
  2. A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13. (PMID: 27182039) Barøy T … Misceo D (European journal of medical genetics 2016) 3 4 54
  3. Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. (PMID: 23993193) Bonnen PE … Taylor RW (American journal of human genetics 2013) 3 4 54
  4. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. (PMID: 23993194) Gai X … Zeviani M (American journal of human genetics 2013) 3 4 54
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54

Products for FBXL4 Gene

Sources for FBXL4 Gene