FBXW2

protein-coding

F-box and WD repeat domain containing 2, the group of WD repeat domain containing|F-box and WD repeat domain containing

Gene summary

F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino acid motif, the F box. Some F-box proteins have been shown to be critical for the ubiquitin-mediated degradation of cellular regulatory proteins. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases, called SCFs. SCF ligases bring ubiquitin conjugating enzymes to substrates that are specifically recruited by the different F-box proteins. Mammalian F-box proteins are classified into three groups based on the presence of either WD-40 repeats, leucine-rich repeats, or the presence or absence of other protein-protein interacting domains. This gene encodes the second identified member of the F-box gene family and contains multiple WD-40 repeats. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012164.4

Inheritance

—

ClinVar variants

U:42B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr9:120,751,978-120,793,416

External References & Databases

Ensembl (ENSG00000119402)

Transcript & Mutation Effects

hg38 • Region Span ~41.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBXW2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 38

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012164.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			39 clinvar	1 clinvar		40
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	42	1	0	43

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 92 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012164.4	RefSeq	NP_036296.2	6	MANE Select
ENST00000608872.6	Ensembl	ENSP00000476369.1	6	MANE Select
NM_001375888.1	RefSeq	NP_001362817.1	6	Standard
NM_001375889.1	RefSeq	NP_001362818.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Wnt Signaling Pathway and Pluripotency
Post-translational protein modification
Metabolism of proteins
Chaperonin-mediated protein folding
Immune System

Biological Process

protein polyubiquitination
cellular protein modification process
proteolysis
post-translational protein modification

Molecular Function

ubiquitin-protein transferase activity
protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000608872
Coding exons: 6
Length: 41435
Individuals with no LoFs: 124792
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 124796
p: 0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.44	137	244	0.561	0.0000126	2990
Missense (PolyPhen)		28	74.33	0.3767		922
Synonymous	-0.170	103	101	1.02	0.00000573	858
Loss of Function	4.09	0	19.5	0.00	8.24e-7	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex.;

Recessive Scores

pRec: 0.0935

Intolerance Scores

LoFtool: 0.199
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.966

Gene Damage Prediction

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