FBXW7

F-box and WD repeat domain containing 7, the group of MicroRNA protein coding host genes|F-box and WD repeat domain containing|WD repeat domain containing

Basic information

Region (hg38): 4:152320543-152536092

Links

ENSG00000109670 ∙ NCBI:55294 ∙ OMIM:606278 ∙ HGNC:16712 ∙ Uniprot:Q969H0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay, hypotonia, and impaired language (Strong), mode of inheritance: AD
• developmental delay, hypotonia, and impaired language (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXW7 gene.

• not provided (42 variants)
• Inborn genetic diseases (21 variants)
• not specified (9 variants)
• Developmental delay, hypotonia, and impaired language (5 variants)
• FBXW7-related condition (5 variants)
• Malignant neoplasm of body of uterus (3 variants)
• Ovarian serous cystadenocarcinoma (3 variants)
• Neoplasm of uterine cervix (3 variants)
• B-cell chronic lymphocytic leukemia (3 variants)
• Neurodevelopmental disorder (3 variants)
• Neoplasm of the large intestine (3 variants)
• Carcinoma of esophagus (3 variants)
• Gastric adenocarcinoma (3 variants)
• Uterine carcinosarcoma (3 variants)
• Squamous cell carcinoma of the head and neck (3 variants)
• Squamous cell lung carcinoma (3 variants)
• Transitional cell carcinoma of the bladder (2 variants)
• Malignant melanoma of skin (2 variants)
• Lung adenocarcinoma (1 variants)
• FBXW7-related neurodevelopmental disorder (1 variants)
• Pervasive developmental disorder (1 variants)
• Medulloblastoma (1 variants)
• FBXW7-Related Disorders (1 variants)
• Predisposition to Wilm's tumor, FBXW7-related (1 variants)
• Adenoid cystic carcinoma (1 variants)
• Breast neoplasm (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXW7 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				14		14
missense	4	6	30		1	41
nonsense	2	2	3			7
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)	1					1
splice region			2			2
non coding			1	2	9	12
Total	7	8	34	16	11

Highest pathogenic variant AF is 0.00000657

Variants in FBXW7

This is a list of pathogenic ClinVar variants found in the FBXW7 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-152322889-T-C			Uncertain significance (Jul 19, 2022)
4-152322939-C-T		Developmental delay, hypotonia, and impaired language	Pathogenic (Aug 26, 2022)
4-152322940-G-A		Developmental delay, hypotonia, and impaired language	Pathogenic (Aug 02, 2023)
4-152322977-T-C		Inborn genetic diseases	Likely benign (Sep 23, 2019)
4-152322979-T-G		Inborn genetic diseases	Likely benign (Sep 24, 2021)
4-152322985-G-A		Developmental delay, hypotonia, and impaired language	Pathogenic (Sep 29, 2023)
4-152322985-G-T		FBXW7-related disorder	Likely benign (Nov 30, 2022)
4-152323032-C-T		Malignant melanoma of skin • Glioblastoma • Malignant neoplasm of body of uterus • Transitional cell carcinoma of the bladder • Uterine carcinosarcoma • Squamous cell carcinoma of the head and neck • Neoplasm of the large intestine • Neoplasm of uterine cervix	Likely pathogenic (May 31, 2016)
4-152323066-T-A		Neurodevelopmental disorder	Likely pathogenic (Jun 03, 2022)
4-152323094-T-C		Inborn genetic diseases • FBXW7-related disorder	Likely benign (Jan 27, 2020)
4-152323101-T-C		Inborn genetic diseases	Uncertain significance (Aug 14, 2023)
4-152323128-G-A		Neurodevelopmental disorder	Likely pathogenic (Feb 02, 2022)
4-152323130-A-C			Uncertain significance (Jan 24, 2022)
4-152323139-C-T			Likely benign (Dec 22, 2023)
4-152324117-G-A			Benign (May 12, 2021)
4-152324168-GGTGA-G			Likely benign (Dec 13, 2023)
4-152324183-C-G		FBXW7-related disorder	Pathogenic (-)
4-152324196-G-A			Uncertain significance (Jun 03, 2022)
4-152324209-T-A		Inborn genetic diseases	Likely benign (Jun 09, 2019)
4-152324246-T-A		FBXW7-related disorder	Likely pathogenic (May 18, 2023)
4-152324254-G-A		Inborn genetic diseases	Likely benign (Mar 13, 2020)
4-152324324-TTC-T		Developmental delay, hypotonia, and impaired language	Pathogenic (Aug 26, 2022)
4-152324347-A-G		Inborn genetic diseases	Likely benign (Dec 25, 2019)
4-152324380-A-G		Inborn genetic diseases • FBXW7-related disorder	Likely benign (Mar 13, 2020)
4-152324388-C-T			Uncertain significance (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXW7	protein_coding	protein_coding	ENST00000281708	11	214844

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000508	125603	0	5	125608	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.71	168	368	0.456	0.0000183	4646
Missense in Polyphen		19	137.51	0.13817		1663
Synonymous	-0.0335	134	134	1.00	0.00000651	1339
Loss of Function	5.23	4	39.5	0.101	0.00000237	427

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000897	0.0000897
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000936	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination (PubMed:22748924, PubMed:17434132, PubMed:26976582, PubMed:28727686). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:29149593, PubMed:25775507, PubMed:28007894, PubMed:26976582, PubMed:28727686). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1 (By similarity). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). {ECO:0000250|UniProtKB:Q8VBV4, ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:26976582, ECO:0000269|PubMed:28007894, ECO:0000269|PubMed:28727686, ECO:0000269|PubMed:29149593, ECO:0000305|PubMed:12354302}.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);NOTCH-Ncore;Parkin-Ubiquitin Proteasomal System pathway;Pathways Affected in Adenoid Cystic Carcinoma;Notch Signaling Pathway;TLR NFkB;Transcriptional regulation by RUNX2;Notch;Signal Transduction;Gene expression (Transcription);cyclin e destruction pathway;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;Chaperonin-mediated protein folding;Notch;Hedgehog;Immune System;Association of TriC/CCT with target proteins during biosynthesis;Adaptive Immune System;Signaling by NOTCH1;Antigen processing: Ubiquitination & Proteasome degradation;IL-1 NFkB;Class I MHC mediated antigen processing & presentation;Signaling by NOTCH;Neddylation;Protein folding;C-MYC pathway;TNFalpha;Wnt Canonical;Validated transcriptional targets of deltaNp63 isoforms;Wnt Mammals;NOTCH1 Intracellular Domain Regulates Transcription;Regulation of RUNX2 expression and activity (Consensus)

Recessive Scores

• pRec: 0.622

Intolerance Scores

• loftool: 0.0563
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.36

Haploinsufficiency Scores

• pHI: 0.986
• hipred: Y
• hipred_score: 0.825
• ghis: 0.509

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbxw7
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; embryo phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; neoplasm; 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); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype

Zebrafish Information Network

• Gene name: fbxw7
• Affected structure: glioblast (sensu Vertebrata)
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: protein polyubiquitination;vasculogenesis;vasculature development;sister chromatid cohesion;Notch signaling pathway;negative regulation of gene expression;negative regulation of triglyceride biosynthetic process;regulation of lipid storage;ubiquitin recycling;viral process;protein ubiquitination;lung development;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;positive regulation of protein ubiquitination;protein destabilization;negative regulation of DNA endoreduplication;regulation of protein localization;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;positive regulation of epidermal growth factor-activated receptor activity;negative regulation of Notch signaling pathway;protein stabilization;positive regulation of ubiquitin-protein transferase activity;lipid homeostasis;positive regulation of ERK1 and ERK2 cascade;regulation of cell migration involved in sprouting angiogenesis;positive regulation of proteasomal protein catabolic process;regulation of cell cycle G1/S phase transition;negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding;regulation of autophagy of mitochondrion;positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway;positive regulation of protein targeting to mitochondrion;positive regulation of ubiquitin-dependent protein catabolic process;negative regulation of hepatocyte proliferation;negative regulation of SREBP signaling pathway;negative regulation of osteoclast development
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;mitochondrion;endoplasmic reticulum;Golgi apparatus;cytosol;SCF ubiquitin ligase complex;perinuclear region of cytoplasm;Parkin-FBXW7-Cul1 ubiquitin ligase complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;cyclin binding;protein binding, bridging;ubiquitin protein ligase binding;identical protein binding;ubiquitin binding;phosphothreonine residue binding;ubiquitin-protein transferase activator activity