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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	10	3	17
missense			58	2	3	63
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			6	8	3	17
Total	0	0	72	20	9

Variants in FBXW4

This is a list of pathogenic ClinVar variants found in the FBXW4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-101610685-T-G		Split hand-foot malformation 3	Uncertain significance (Jan 13, 2018)
10-101610691-C-T		Split hand-foot malformation 3	Uncertain significance (Jan 13, 2018)
10-101610838-G-A		Split hand-foot malformation 3	Likely benign (Jan 13, 2018)
10-101610910-G-C		Split hand-foot malformation 3	Uncertain significance (Jan 13, 2018)
10-101610976-T-TAATA		Ectrodactyly	Uncertain significance (Jun 14, 2016)
10-101611032-G-A		Split hand-foot malformation 3	Benign (Jan 12, 2018)
10-101611058-C-A		Split hand-foot malformation 3	Likely benign (Jan 12, 2018)
10-101611087-C-T		Split hand-foot malformation 3	Likely benign (Jan 13, 2018)
10-101611284-C-G		Split hand-foot malformation 3	Benign (May 04, 2021)
10-101611288-C-T		Split hand-foot malformation 3	Likely benign (Jan 13, 2018)
10-101611298-T-C		not specified	Uncertain significance (May 10, 2024)
10-101611302-G-C			Uncertain significance (May 07, 2023)
10-101611314-C-T		not specified	Uncertain significance (Mar 08, 2025)
10-101611315-G-T			Uncertain significance (Oct 28, 2023)
10-101611315-G-GTGGAGGT		See cases	Uncertain significance (Jun 12, 2019)
10-101611330-CAG-C		See cases	Uncertain significance (Jun 12, 2019)
10-101611338-C-T		Split hand-foot malformation 3 • not specified	Uncertain significance (Aug 12, 2021)
10-101611340-T-A		not specified	Uncertain significance (Jan 18, 2025)
10-101611361-C-T			Uncertain significance (Jan 03, 2024)
10-101611362-G-A			Uncertain significance (Mar 19, 2023)
10-101611371-A-G		not specified	Uncertain significance (May 28, 2024)
10-101611388-G-C		not specified	Uncertain significance (Nov 09, 2024)
10-101611402-C-T			Likely benign (Nov 27, 2024)
10-101611638-G-T		not specified	Uncertain significance (Jul 06, 2021)
10-101611650-C-T		not specified	Uncertain significance (Jul 23, 2024)

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