GeneBe

FBXW8

F-box and WD repeat domain containing 8, the group of F-box and WD repeat domain containing|WD repeat domain containing

Basic information

Region (hg38): 12:116910950-117032498

Previous symbols: [ "FBXO29" ]

Links

ENSG00000174989 ∙ NCBI:26259 ∙ OMIM:609073 ∙ HGNC:13597 ∙ Uniprot:Q8N3Y1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXW8 gene.

  • not_specified (87 variants)
  • not_provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXW8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153348.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
 3
missense
81
clinvar
6
clinvar
3
clinvar
 90
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total 0 0 81 7 5
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FBXW8protein_codingprotein_codingENST00000309909 11120193
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.24e-160.025412488938561257480.00342
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.1193223280.9820.00002013881
Missense in Polyphen7879.7080.97857909
Synonymous0.2041331360.9780.000009961187
Loss of Function0.4462527.50.9080.00000136309

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.003200.00319
Ashkenazi Jewish0.001190.00119
East Asian0.001200.00114
Finnish0.005310.00528
European (Non-Finnish)0.005390.00539
Middle Eastern0.001200.00114
South Asian0.0003920.000392
Other0.002440.00245

dbNSFP

Source: dbNSFP

Function
FUNCTION: Substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The Cul7-RING(FBXW8) complex mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain (PubMed:21572988). Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2) (PubMed:18498745). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation (PubMed:24362026). Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions (PubMed:24793695). {ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695}.;
Pathway
Ubiquitin mediated proteolysis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation (Consensus)

Recessive Scores

pRec
0.274

Intolerance Scores

loftool
0.995
rvis_EVS
-0.28
rvis_percentile_EVS
33.49

Haploinsufficiency Scores

pHI
0.199
hipred
Y
hipred_score
0.685
ghis
0.562

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.868

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Fbxw8
Phenotype
growth/size/body region phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo 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); 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); 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);

Gene ontology

Biological process
protein polyubiquitination;Golgi organization;cell population proliferation;protein ubiquitination;post-translational protein modification;positive regulation of dendrite morphogenesis;spongiotrophoblast layer development;labyrinthine layer blood vessel development;positive regulation of transcription factor catabolic process
Cellular component
Golgi apparatus;cytosol;SCF ubiquitin ligase complex;Cul7-RING ubiquitin ligase complex;perinuclear region of cytoplasm;3M complex
Molecular function
ubiquitin-protein transferase activity;protein binding