FBXO43

Chr 8AR

F-box protein 43

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

NCBI Gene: 286151 ENSG00000156509 OMIM: 609110

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.812 OMIM phenotypes

Clinical Summary— FBXO43

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 82 VUS of 107 total submissions

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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 OE?0.50 (0.32–0.81)

0≤0.351.4

Missense OE?0.90 (0.82–0.99)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 12 / 24.0Missense obs/exp: 324 / 359.8Syn Z: 0.15

This gene — mechanism propensity

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

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

VUS82

Likely Benign11

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	3	1	0	4
Likely Pathogenic	0	0	0	0
VUS	0	82	0	82
Likely Benign	0	7	4	11
Benign	0	1	0	1
Total	3	91	4	98

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap FBXO43 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →