FBXO43

protein-coding

F-box protein 43, the group of F-boxes other

Gene summary

Members of the F-box protein family, such as FBXO43, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001029860.4

Inheritance

ClinVar variants

P:6U:88B:13

Top phenotype

Spermatogenic failure 64; Oocyte maturation defect 12

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr8:100,133,351-100,145,817

External References & Databases

Ensembl (ENSG00000156509)

Transcript & Mutation Effects

hg38 • Region Span ~12.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oocyte maturation defect 12LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030523

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 64LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030522

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 64; Oocyte maturation defect 12AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30878252; 34052850; 34595750

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBXO43 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 9

Oocyte maturation defect 12Total: 5

Spermatogenic failure 64Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001029860.4. 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			2 clinvar	5 clinvar		7
missense	1 clinvar		86 clinvar	7 clinvar	1 clinvar	95
nonsense	2 clinvar					2
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)						0
Total	5	1	88	12	1	107

Highest pathogenic variant AF is 0.0000012391728

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001029860.4	RefSeq	NP_001025031.2	5	MANE Select
ENST00000428847.3	Ensembl	ENSP00000403293.2	5	MANE Select
ENST00000517806.5	Ensembl	ENSP00000429759.1	1	Standard
ENST00001114164.1	Ensembl	ENSP00000783969.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oocyte meiosis - Homo sapiens (human)

Biological Process

protein ubiquitination
negative regulation of meiotic nuclear division
meiotic cell cycle

Molecular Function

metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428847
Coding exons: 5
Length: 12441
Individuals with no LoFs: 124732
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 124795
p: 0.000252

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.670	324	360	0.901	0.0000176	4641
Missense (PolyPhen)		50	79.19	0.63139		928
Synonymous	0.146	131	133	0.984	0.00000661	1351
Loss of Function	2.27	12	24.0	0.499	0.00000108	371

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00013	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.000099	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. Probably acts by inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation (Probable). {ECO:0000305}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.778
RVIS EVS: 0.04
RVIS percentile EVS: 57.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.253

Gene Damage Prediction

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