FBXW4

Chr 10

F-box and WD repeat domain containing 4

Also known as: DAC, FBW4, FBWD4, SHFM3, SHSF3

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSplit-hand/foot malformation 3
0
Active trials
3
Pubs (1 yr)
P/LP submissions
P/LP missense
0.72
LOEUF
DN
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.72LOEUF
pLI 0.001
Z-score 2.53
OE 0.41 (0.250.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.43Z-score
OE missense 0.73 (0.650.83)
167 obs / 227.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.41 (0.250.72)
00.351.4
Missense OE?0.73 (0.650.83)
00.61.4
Synonymous OE?0.89
01.21.6
LoF obs/exp: 9 / 21.7Missense obs/exp: 167 / 227.6Syn Z: 0.81

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FBXW4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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