FBXO7

protein-coding

F-box protein 7, the group of F-boxes other

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 Fbxs class and it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012179.4

Inheritance

ClinVar variants

P:47U:145B:144

Top phenotype

Parkinson disease 15, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr22:32,474,676-32,498,829

External References & Databases

Ensembl (ENSG00000100225)

Transcript & Mutation Effects

hg38 • Region Span ~24.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

parkinsonian-pyramidal syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009830

Submitter: PanelApp Australia

parkinsonian-pyramidal syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009830

Submitter: Orphanet

parkinsonian-pyramidal syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009830

Submitter: Labcorp Genetics (formerly Invitae)

parkinsonian-pyramidal syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009830

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Parkinson disease 15, autosomal recessiveAR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Individuals have been described with levodopa response

Refs: 18513678; 19038853; 23318512

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBXO7 variants in ClinVar

5 Conditions Cataloged

Parkinsonian-pyramidal syndromeTotal: 335

not providedTotal: 65

Inborn genetic diseasesTotal: 60

not specifiedTotal: 12

FBXO7-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012179.4. 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			4 clinvar	125 clinvar	2 clinvar	131
missense	1 clinvar	1 clinvar	133 clinvar	16 clinvar	1 clinvar	152
nonsense	9 clinvar	8 clinvar	1 clinvar			18
start loss	4 clinvar					4
frameshift	14 clinvar	5 clinvar	2 clinvar			21
splice donor/acceptor (+/-2bp)	1 clinvar	4 clinvar	5 clinvar			10
Total	29	18	145	141	3	336

Highest pathogenic variant AF is 0.000096032556

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012179.4	RefSeq	NP_036311.3	9	MANE Select
ENST00000266087.12	Ensembl	ENSP00000266087.7	9	MANE Select
NM_001033024.2	RefSeq	NP_001028196.1	9	Standard
NM_001257990.2	RefSeq	NP_001244919.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fbxo7	Danio rerio	Structure: post-vent region Quality: curled abnormal

Gene / Model

Organism

Observed Phenotype

fbxo7

Danio rerio

Structure: post-vent region

Quality: curled

abnormal

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
autophagy of mitochondrion
ubiquitin-dependent protein catabolic process
protein targeting to mitochondrion
regulation of neuron projection development

Molecular Function

ubiquitin-protein transferase activity
protein binding
protein kinase binding
ubiquitin protein ligase binding
ubiquitin binding

Cellular Component

ubiquitin ligase complex
nucleus
cytoplasm
mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266087
Coding exons: 9
Length: 24156
Individuals with no LoFs: 125687
Homozygous LoFs: 0
Heterozygous LoFs: 61
Defined: 125748
p: 0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.440	305	284	1.07	0.0000161	3359
Missense (PolyPhen)		85	81.16	1.0473		960
Synonymous	0.626	105	113	0.925	0.00000645	1081
Loss of Function	2.03	14	25.0	0.561	0.00000150	286

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00033	0.00033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes BIRC2 and DLGAP5. Plays a role downstream of PINK1 in the clearance of damaged mitochondria via selective autophagy (mitophagy) by targeting PRKN to dysfunctional depolarized mitochondria. Promotes MFN1 ubiquitination. {ECO:0000269|PubMed:15145941, ECO:0000269|PubMed:16510124, ECO:0000269|PubMed:23933751}.;
Disease: DISEASE: Parkinson disease 15 (PARK15) [MIM:260300]: A neurodegenerative disorder characterized by parkinsonian and pyramidal signs. Clinical manifestations include tremor, bradykinesia, rigidity, postural instability, spasticity, mainly in the lower limbs, and hyperreflexia. {ECO:0000269|PubMed:18513678, ECO:0000269|PubMed:23933751}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.893
RVIS EVS: 0.09
RVIS percentile EVS: 60.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.294

Gene Damage Prediction

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