FBXL8

protein-coding

F-box and leucine rich repeat protein 8, the group of F-box and leucine rich repeat proteins

Gene summary

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class. It shares 78% sequence identity with the mouse protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_018378.3

Inheritance

—

ClinVar variants

U:70B:9

Top phenotype

Cataract 5 multiple types

gnomAD constraint

pLI —, LoF o/e 1.42

Max pathogenic AF

—

Genomic locus

chr16:67,159,932-67,164,570

External References & Databases

Ensembl (ENSG00000135722)

Transcript & Mutation Effects

hg38 • Region Span ~4.6 kb

Loading mutation effect viewer...

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 FBXL8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 69

Cataract 5 multiple typesTotal: 10

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018378.3. 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			1 clinvar		1 clinvar	2
missense			68 clinvar	3 clinvar	5 clinvar	76
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	70	3	6	79

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018378.3	RefSeq	NP_060848.2	2	MANE Select
ENST00000258200.8	Ensembl	ENSP00000258200.3	2	MANE Select
ENST00000517382.5	Ensembl	ENSP00000430745.1	3	Standard
ENST00000518148.1	Ensembl	ENSP00000464169.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

protein polyubiquitination
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
post-translational protein modification

Molecular Function

ubiquitin-protein transferase activity
protein binding
ubiquitin protein ligase activity

Cellular Component

cytosol
SCF ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258200
Coding exons: 2
Length: 4640
Individuals with no LoFs: 121333
Homozygous LoFs: 81
Heterozygous LoFs: 3080
Defined: 124494
p: 0.0128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.196	196	204	0.961	0.0000103	2270
Missense (PolyPhen)		22	29.253	0.75207		294
Synonymous	1.94	73	97.4	0.749	0.00000513	863
Loss of Function	-1.09	11	7.73	1.42	3.35e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00081	0.00075	rare
Latino/Admixed American	0.038	0.036	notable
Ashkenazi Jewish	0.00010	0.00010	rare
East Asian	0.064	0.062	notable
Finnish	0.0049	0.0039	notable
European (Non-Finnish)	0.00043	0.00040	rare
South Asian	0.022	0.021	notable
Other	0.0099	0.0093	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex. {ECO:0000250}.;

Recessive Scores

pRec: 0.103

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.361

Gene Damage Prediction

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