FBXO43

Chr 8AR

F-box protein 43

Also known as: EMI2, ERP1, FBX43, OOMD12, OZEMA12, SPGF64

NCBI Gene: 286151ENSG00000156509UniProt: Q4G163

FBXO43 encodes an F-box protein that functions as part of SCF ubiquitin ligase complexes and is specifically required to maintain arrest of oocytes at the second meiotic metaphase until fertilization by inhibiting the anaphase-promoting complex. Biallelic mutations cause autosomal recessive oocyte/zygote/embryo maturation arrest and spermatogenic failure, affecting reproductive function rather than neurological development. This gene shows low constraint against loss-of-function variants (pLI near 0), consistent with its specialized role in gametogenesis.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Oocyte/zygote/embryo maturation arrest 12MIM #619697
AR
Spermatogenic failure 64MIM #619696
AR
0
Active trials
3
Pubs (1 yr)
41
P/LP submissions
3%
P/LP missense
0.81
LOEUF
DN
Mechanism· predicted
Clinical Summary— FBXO43
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 86 VUS of 147 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.27
OE 0.50 (0.32–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.67Z-score
OE missense 0.90 (0.82–0.99)
324 obs / 359.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.32–0.81)
0≤0.351.4
Missense OE0.90 (0.82–0.99)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 12 / 24.0Missense obs/exp: 324 / 359.8Syn Z: 0.15
DN
0.6550th %ile
GOF
0.3590th %ile
LOF
0.4529th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic1
VUS86
Likely Benign11
Benign1
39
Pathogenic
1
Likely Pathogenic
86
VUS
11
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
37
0
39
Likely Pathogenic
0
0
1
0
1
VUS
0
79
7
0
86
Likely Benign
0
7
0
4
11
Benign
0
1
0
0
1
Total188454138

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FBXO43 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients