• 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
FBXW4 (HGNC:10847) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
F-box and WD repeat domain containing 4
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
SHFM3
Alias symbols
Fbw4, dactylin
%HI
16.23(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.72(Read more about gnomAD LOEUF score)
Cytoband
10q24.32
Genomic Coordinates
GRCh37/hg19: chr10:103370423-103455052 NCBI Ensembl UCSC
GRCh38/hg38: chr10:101610666-101695295 NCBI Ensembl UCSC
MANE Select Transcript
NM_022039.4 ENST00000331272.9 (Read more about MANE Select)
Function
Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. Likely to be involved in key signaling pathways crucial for normal limb development. May participate in Wnt signaling. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-10149
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
10/08/2014

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence Comments:
PMID: 12913067 De Mollerat (2003): This is a report of 7 patients with SHFM3 (split hand/foot malformation 3) who all had a tandem duplication which included LBX1, BTRC, and POLL, and had a breakpoint within FBXW4 (DAC), potentially disrupting this gene. PMID: 23596994 Dai (2013): A report of a four-generation Chinese family with SHFM3 that co-segregates with a discontinuous duplication of the 10q24 region which includes a portion of FBXW4. Also of note, in 2013, Vergult et al. (PMID: 22995989) reported an 80.2 kb deletion involving only FBXW4 in a European individual with a radial ray defect. This deletion was inherited from a reportedly phenotypically normal mother. No sequence variants were found in FBXW4 on the other chromosome. This group then sequenced the coding regions and 6 conserved non-coding elements of the gene in a larger cohort of 54 European individuals with radial ray defects. They detected a g.103380009A>G variant in an individual with bilateral radial dysplasia for whom no parental samples were available. This variant was not detected in 96 ethnicity-matched controls or in the 1000 Genomes cohort. No functional studies were performed. Based on this evidence alone, it is unclear whether haploinsufficiency of FBXW4 plays a role in radial ray defects.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Disease:
  • split hand-foot malformation 3 Monarch
TS Evidence Comments:
Tandem duplications at 10q24 are associated with split hand/foot malformation 3 (SHFM3) syndrome: PMID: 16235095 Kano (2005): This report includes 2 patients with SHFM3 who had similar duplications. One duplication including all of BTRC, POLL, and DPCD, and had a breakpoint within FBXW4 (DAC). The other duplication extended distally to encompass all of FBXW4. PMID: 19584065 Dimitrov (2010): This paper includes 6 patients with both syndromic and non-syndromic SHFM3 who have duplications at 10q24 of varying size, which include FBXW4. They comment on genotype-phenotype correlations. PMID: 21485001 Filho (2011): A report of two brothers with syndromic SHFM3 who have 10q24 duplications that include all of FBXW4. Their mother was found to have somatic mosaicism for this duplication.

Genomic View

Select assembly: (NC_000010.10) (NC_000010.11)