FBXW4

F-box and WD repeat domain containing 4, the group of F-box and WD repeat domain containing|WD repeat domain containing

Basic information

Region (hg38): 10:101610664-101695295

Previous symbols: [ "SHFM3" ]

Links

ENSG00000107829

∙ NCBI:6468 ∙ OMIM:608071 ∙ HGNC:10847 ∙ Uniprot:P57775 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

split hand-foot malformation 3 (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXW4 gene.

not_specified (53 variants)
not_provided (52 variants)
Split_hand-foot_malformation_3 (29 variants)
FBXW4-related_disorder (6 variants)
Ectrodactyly (3 variants)
See_cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXW4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022039.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	9 clinvar	3 clinvar	16
missense			76 clinvar	3 clinvar	2 clinvar	81
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	83	12	5

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXW4	protein_coding	protein_coding	ENST00000331272	9	84630

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000676	0.996	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	167	228	0.734	0.0000130	2622
Missense in Polyphen		42	56.464	0.74384		596
Synonymous	0.814	83	93.0	0.893	0.00000520	848
Loss of Function	2.53	9	21.7	0.414	0.00000130	217

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.000197	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: 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.;
Pathway: Post-translational protein modification;Metabolism of proteins;Chaperonin-mediated protein folding;Immune System;Association of TriC/CCT with target proteins during biosynthesis;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation;Protein folding (Consensus)

Recessive Scores

pRec: 0.116

Intolerance Scores

loftool: 0.459
rvis_EVS: -0.63
rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

pHI: 0.174
hipred: N
hipred_score: 0.285
ghis: 0.579

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.645

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Fbxw4
Phenotype: skeleton phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); limbs/digits/tail phenotype;

Zebrafish Information Network

Gene name: fbxw4
Affected structure: pigment cell
Phenotype tag: abnormal
Phenotype quality: irregular spatial pattern

Gene ontology

Biological process: protein polyubiquitination;positive regulation of mesenchymal cell proliferation;ubiquitin-dependent protein catabolic process;Wnt signaling pathway;embryonic limb morphogenesis;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;embryonic digit morphogenesis;post-translational protein modification;cartilage development
Cellular component: ubiquitin ligase complex;cytosol;SCF ubiquitin ligase complex
Molecular function: molecular_function;ubiquitin-protein transferase activity;protein binding