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.

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.

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				1	1	2
missense			37	2	3	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	37	3	4

Variants in FBXW8

This is a list of pathogenic ClinVar variants found in the FBXW8 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-116911062-T-G		not specified	Uncertain significance (Aug 16, 2021)
12-116911066-G-A		not specified	Uncertain significance (Oct 06, 2021)
12-116911094-G-T		not specified	Uncertain significance (Sep 25, 2023)
12-116911113-C-G		not specified	Uncertain significance (Feb 06, 2024)
12-116911123-C-T		not specified	Uncertain significance (Jul 11, 2023)
12-116911259-C-T			Benign (Jun 28, 2018)
12-116911276-C-G		not specified	Uncertain significance (Jun 11, 2021)
12-116911300-C-G		not specified	Uncertain significance (Sep 16, 2021)
12-116911336-A-G		not specified	Uncertain significance (May 24, 2023)
12-116911347-C-T		not specified	Uncertain significance (Oct 14, 2023)
12-116911350-G-C		not specified	Uncertain significance (Dec 20, 2021)
12-116928037-T-C			Likely benign (Mar 30, 2018)
12-116928063-C-T		not specified	Uncertain significance (Feb 28, 2024)
12-116945382-G-A		not specified	Uncertain significance (May 18, 2022)
12-116945401-T-A		not specified	Uncertain significance (Oct 06, 2022)
12-116945461-A-G		not specified	Uncertain significance (Oct 20, 2023)
12-116949614-G-A			Benign (Jun 18, 2018)
12-116949622-G-A		not specified	Uncertain significance (Aug 17, 2021)
12-116949660-A-G			Benign (Jul 04, 2018)
12-116949699-A-G		not specified	Uncertain significance (Jul 07, 2022)
12-116964707-G-A		not specified	Uncertain significance (Aug 11, 2022)
12-116964793-G-A		not specified	Uncertain significance (Jan 06, 2023)
12-116985224-A-G		not specified	Uncertain significance (Nov 08, 2022)
12-116985298-G-C		not specified	Uncertain significance (Feb 23, 2023)
12-116985301-G-A		not specified	Uncertain significance (Feb 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXW8	protein_coding	protein_coding	ENST00000309909	11	120193

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.24e-16	0.0254	124889	3	856	125748	0.00342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.119	322	328	0.982	0.0000201	3881
Missense in Polyphen		78	79.708	0.97857		909
Synonymous	0.204	133	136	0.978	0.00000996	1187
Loss of Function	0.446	25	27.5	0.908	0.00000136	309

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00320	0.00319
Ashkenazi Jewish	0.00119	0.00119
East Asian	0.00120	0.00114
Finnish	0.00531	0.00528
European (Non-Finnish)	0.00539	0.00539
Middle Eastern	0.00120	0.00114
South Asian	0.000392	0.000392
Other	0.00244	0.00245

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

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

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