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FBXW4 F-box and WD repeat domain containing 4 [ Homo sapiens (human) ]

Gene ID: 6468, updated on 5-Mar-2024

Summary

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Official Symbol
FBXW4provided by HGNC
Official Full Name
F-box and WD repeat domain containing 4provided by HGNC
Primary source
HGNC:HGNC:10847
See related
Ensembl:ENSG00000107829 MIM:608071; AllianceGenome:HGNC:10847
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
DAC; FBW4; FBWD4; SHFM3; SHSF3
Summary
This gene is a member of the F-box/WD-40 gene family, which recruit specific target proteins through their WD-40 protein-protein binding domains for ubiquitin mediated degradation. In mouse, a highly similar protein is thought to be responsible for maintaining the apical ectodermal ridge of developing limb buds; disruption of the mouse gene results in the absence of central digits, underdeveloped or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar to split hand-split foot malformation in humans, a clinically heterogeneous condition with a variety of modes of transmission. An autosomal recessive form has been mapped to the chromosomal region where this gene is located, and complex rearrangements involving duplications of this gene and others have been associated with the condition. A pseudogene of this locus has been mapped to one of the introns of the BCR gene on chromosome 22. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in fat (RPKM 17.7), lung (RPKM 17.4) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
10q24.32
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (101610666..101695295, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (102494739..102578296, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (103370423..103455052, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3912 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3913 Neighboring gene NANOG hESC enhancer GRCh37_chr10:103356755-103357323 Neighboring gene DNA polymerase lambda Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2722 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:103367960-103368675 Neighboring gene deleted in primary ciliary dyskinesia homolog (mouse) Neighboring gene microRNA 3158-1 Neighboring gene microRNA 3158-2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103371133-103371633 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103372791-103373324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103373325-103373858 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103378239-103379151 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103379197-103379698 Neighboring gene RNA, U6 small nuclear 1165, pseudogene Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:103402902-103403748 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:103403749-103404596 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2723 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2724 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2725 Neighboring gene long intergenic non-protein coding RNA 3046 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103483003-103483722 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:103489563-103490062 Neighboring gene uncharacterized LOC105378458 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:103517739-103518240 Neighboring gene VISTA enhancer hs511

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. Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non-syndromic split-hand/foot malformation. Everman DB, et al. Am J Med Genet A, 2006 Jul 1. PMID 16761290
  2. Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation. Kano H, et al. Hum Genet, 2005 Dec. PMID 16235095
  3. Molecular genetic characterization of a Korean split hand/split foot malformation (SHFM). Kang YS, et al. Mol Cells, 2004 Jun 30. PMID 15232212
  4. The 10q24-linked split hand/split foot syndrome (SHFM3): narrowing of the critical region and confirmation of the clinical phenotype. Roscioli T, et al. Am J Med Genet A, 2004 Jan 15. PMID 14699611
  5. Split hand foot malformation is associated with a reduced level of Dactylin gene expression. Basel D, et al. Clin Genet, 2003 Oct. PMID 12974740

See all (37) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. biochemical characterization of the novel F-box and WD40 containing protein, FBXW4
    Title: The novel ubiquitin ligase complex, SCF(Fbxw4), interacts with the COP9 signalosome in an F-box dependent manner, is mutated, lost and under-expressed in human cancers.
  2. results indicate that genomic rearrangement of SHFM3 is rare among non-syndromic SHFM patients and emphasize the importance of screening for genomic rearrangements even in sporadic cases of SHFM
    Title: Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation.
  3. Genomic rearrangements involving the SHFM3 locus at chromosome 10q24 is associated with syndromic and non-syndromic split-hand/foot malformation
    Title: Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non-syndromic split-hand/foot malformation.
  4. a complex rearrangement associated with a approximately 0.5 Mb tandem duplication ion containing a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and beta-TRCP genes.
    Title: A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24.
Submit: New GeneRIF Correction

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

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2014-10-08)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2014-10-08)

ClinGen Genome Curation Page

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
  
involved_in Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in embryonic limb morphogenesis 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
part_of SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of ubiquitin ligase complex NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
F-box/WD repeat-containing protein 4
Names
F-box and WD-40 domain protein 4
F-box and WD-40 domain-containing protein 4
F-box/WD repeat protein 4
dactylin
epididymis secretory sperm binding protein

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_008091.1 RefSeqGene

    Range
    4817..89321
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001323541.2 → NP_001310470.1  F-box/WD repeat-containing protein 4 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC010789, AL627144, AL627424

  2. NM_022039.4 → NP_071322.2  F-box/WD repeat-containing protein 4 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AF281859
    Consensus CDS
    CCDS31271.2
    UniProtKB/TrEMBL
    A0A5F9UQ55
    Related
    ENSP00000359149.3, ENST00000331272.9

RNA

  1. NR_136613.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010789, AL627144, AL627424
    Related
    ENST00000664783.1

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_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    101610666..101695295 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    102494739..102578296 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P57775.1 GenPept UniProtKB/Swiss-Prot:P57775

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