FBXL6

protein-coding

F-box and leucine rich repeat protein 6, the group of F-box and leucine rich repeat proteins

Gene summary

This gene encodes a member of a family of proteins that are characterized by an F-box motif. The encoded protein also contains leucine-rich repeats. F-box-containing proteins comprise one of the subunits of the SCF (SKP1-cullin-F-box) complex, which functions in phosphorylation-dependent ubiquitination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

MANE transcript

NM_012162.4

Inheritance

—

ClinVar variants

U:126B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr8:144,355,431-144,359,376

External References & Databases

Ensembl (ENSG00000182325)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 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 FBXL6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 113

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012162.4. 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			3 clinvar	4 clinvar		7
missense			114 clinvar	8 clinvar		122
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	126	12	0	138

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012162.4	RefSeq	NP_036294.2	9	MANE Select
ENST00000331890.6	Ensembl	ENSP00000330098.5	9	MANE Select
NM_024555.6	RefSeq	NP_078831.4	9	Standard
ENST00000455319.6	Ensembl	ENSP00000403873.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
protein ubiquitination
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

Molecular Function

ubiquitin-protein transferase activity
ubiquitin protein ligase activity

Cellular Component

SCF ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331890
Coding exons: 9
Length: 3946
Individuals with no LoFs: 125566
Homozygous LoFs: 0
Heterozygous LoFs: 128
Defined: 125694
p: 0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.08	329	278	1.18	0.0000165	3339
Missense (PolyPhen)		108	93.06	1.1605		1106
Synonymous	-3.70	178	125	1.42	0.00000717	1224
Loss of Function	1.19	16	22.0	0.727	0.00000121	238

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00036	0.00031	rare
Latino/Admixed American	0.00021	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0022	0.0022	notable
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00053	0.00053	rare
South Asian	0.00027	0.00026	rare
Other	0.00066	0.00065	rare

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: 0.101

Intolerance Scores

LoFtool: 0.876
RVIS EVS: -0.44
RVIS percentile EVS: 24.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.893

Gene Damage Prediction

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