FBXO7

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

Basic information

Region (hg38): 22:32474676-32498829

Links

ENSG00000100225 ∙ NCBI:25793 ∙ OMIM:605648 ∙ HGNC:13586 ∙ Uniprot:Q9Y3I1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• parkinsonian-pyramidal syndrome (Strong), mode of inheritance: AR
• parkinsonian-pyramidal syndrome (Strong), mode of inheritance: AR
• parkinsonian-pyramidal syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 15, autosomal recessive	AR	Neurologic	Individuals have been described with levodopa response	Neurologic	18513678; 19038853; 23318512

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXO7 gene.

• Parkinsonian-pyramidal syndrome (31 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXO7 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			2	109	2	113
missense	1		87	13	2	103
nonsense	12	3				15
start loss	4					4
frameshift	13	1	2			16
inframe indel						0
splice donor/acceptor (+/-2bp)	1	4	1			6
splice region			3	16	2	21
non coding			12	65	26	103
Total	31	8	104	187	30

Highest pathogenic variant AF is 0.0000197

Variants in FBXO7

This is a list of pathogenic ClinVar variants found in the FBXO7 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-32474735-C-G		Parkinson Disease, Recessive	Uncertain significance (Jun 14, 2016)
22-32474771-G-C		Parkinson Disease, Recessive	Uncertain significance (Jun 14, 2016)
22-32474782-C-T		Parkinson Disease, Recessive	Benign (Jul 05, 2018)
22-32474803-G-A		Parkinson Disease, Recessive	Uncertain significance (Jun 14, 2016)
22-32474806-C-T		Parkinson Disease, Recessive	Uncertain significance (Jun 14, 2016)
22-32474819-C-T		Parkinsonian-pyramidal syndrome	Benign (Aug 21, 2018)
22-32474835-A-G		Parkinsonian-pyramidal syndrome	Uncertain significance (Jan 13, 2018)
22-32474873-C-T		Parkinsonian-pyramidal syndrome	Uncertain significance (Apr 28, 2017)
22-32474885-T-G		Parkinsonian-pyramidal syndrome	Uncertain significance (Jan 13, 2018)
22-32474906-C-T		Parkinsonian-pyramidal syndrome	Uncertain significance (Jan 13, 2018)
22-32474910-G-A		Parkinsonian-pyramidal syndrome	Uncertain significance (Jan 12, 2018)
22-32475003-A-C		Parkinsonian-pyramidal syndrome	Pathogenic (Nov 15, 2023)
22-32475003-A-G		Parkinsonian-pyramidal syndrome	Pathogenic (Aug 08, 2023)
22-32475004-T-A		Parkinsonian-pyramidal syndrome	Pathogenic (Sep 19, 2023)
22-32475004-T-G		Parkinsonian-pyramidal syndrome	Pathogenic (May 31, 2023)
22-32475006-A-C		Parkinsonian-pyramidal syndrome	Likely benign (Dec 13, 2023)
22-32475021-C-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
22-32475031-G-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
22-32475032-G-A		Parkinsonian-pyramidal syndrome	Likely benign (Oct 20, 2023)
22-32475034-C-T		Parkinsonian-pyramidal syndrome	Uncertain significance (Aug 30, 2021)
22-32475035-C-G		Parkinsonian-pyramidal syndrome	Likely benign (Feb 14, 2023)
22-32475035-C-T		Parkinsonian-pyramidal syndrome	Likely benign (May 13, 2023)
22-32475042-C-T		Parkinsonian-pyramidal syndrome	Likely benign (Jan 16, 2024)
22-32475043-T-G		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
22-32475047-G-A		Parkinsonian-pyramidal syndrome	Likely benign (Dec 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXO7	protein_coding	protein_coding	ENST00000266087	9	24156

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.79e-7	0.969	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.440	305	284	1.07	0.0000161	3359
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000420	0.000420
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000334	0.000334
Middle Eastern	0.0000544	0.0000544
South Asian	0.000328	0.000327
Other	0.000326	0.000326

dbNSFP

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.
• Pathway: 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: 0.138

Intolerance Scores

• loftool: 0.893
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.57

Haploinsufficiency Scores

• pHI: 0.0684
• hipred: Y
• hipred_score: 0.614
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.294

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbxo7
• Phenotype: homeostasis/metabolism phenotype; reproductive system phenotype; hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: fbxo7
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: protein polyubiquitination;autophagy of mitochondrion;ubiquitin-dependent protein catabolic process;protein targeting to mitochondrion;regulation of neuron projection development;protein ubiquitination;regulation of protein stability;regulation of locomotion;post-translational protein modification;negative regulation of lymphocyte differentiation;negative regulation of cyclin-dependent protein serine/threonine kinase activity;negative regulation of oxidative stress-induced neuron death;positive regulation of autophagy of mitochondrion;negative regulation of G1/S transition of mitotic cell cycle
• Cellular component: ubiquitin ligase complex;nucleus;cytoplasm;mitochondrion;cytosol;SCF ubiquitin ligase complex;protein-containing complex;glial cytoplasmic inclusion;classical Lewy body;Lewy neurite;Lewy body core;Lewy body corona
• Molecular function: ubiquitin-protein transferase activity;protein binding;protein kinase binding;ubiquitin protein ligase binding;ubiquitin binding;protein heterodimerization activity