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): 4:152320544-152536092
Links
Phenotypes
GenCC
Source:
- developmental delay, hypotonia, and impaired language (Strong), mode of inheritance: AD
- developmental delay, hypotonia, and impaired language (Strong), mode of inheritance: AD
- developmental delay, hypotonia, and impaired language (Moderate), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (119 variants)
- Inborn_genetic_diseases (39 variants)
- FBXW7-related_disorder (26 variants)
- Developmental_delay,_hypotonia,_and_impaired_language (22 variants)
- not_specified (13 variants)
- Neurodevelopmental_disorder (3 variants)
- Pervasive_developmental_disorder (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- FBXW7-related_neurodevelopmental_disorder (1 variants)
- Predisposition_to_Wilm's_tumor,_FBXW7-related (1 variants)
- Developmental_delay (1 variants)
- Colorectal_cancer (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. These statistics are base on transcript: NM_001349798.2. 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 | 24 | 29 | ||||
| missense | 97 | 118 | ||||
| nonsense | 7 | |||||
| start loss | 0 | |||||
| frameshift | 11 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 13 | 18 | 100 | 28 | 7 |
Highest pathogenic variant AF is 0.00000138828
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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