FBXO31

Chr 16AR

F-box protein 31

Also known as: FBX14, FBXO14, Fbx31, MRT45, pp2386

NCBI Gene: 79791 ENSG00000103264 UniProt: Q5XUX0 OMIM: 609102

FBXO31 encodes a substrate-recognition component of the SCF ubiquitin ligase complex that targets specific proteins for degradation, including cell cycle regulators like cyclin-D1 and cyclin-A, and DNA damage response proteins like MDM2, thereby maintaining genomic integrity and proper cell cycle control. Biallelic mutations cause autosomal recessive intellectual developmental disorder-45 through disruption of these critical cellular processes. The pathogenic mechanism involves loss of proper protein degradation leading to dysregulated cell cycle progression and impaired DNA damage responses.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.461 OMIM phenotype

Clinical Summary— FBXO31

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 83 VUS of 132 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.444

Z-score 3.48

OE 0.22 (0.11–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.46Z-score

OE missense 0.63 (0.56–0.70)

214 obs / 342.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.11–0.46)

0≤0.351.4

Missense OE?0.63 (0.56–0.70)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 5 / 23.0Missense obs/exp: 214 / 342.0Syn Z: -0.44

ClinVar Variant Classifications

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS83

Likely Benign24

Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	1	1	0	0	2
VUS	1	75	4	3	83
Likely Benign	0	3	1	20	24
Benign	0	0	2	3	5
Total	3	79	7	26	115

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 68) ClinVar copy-number / structural variants overlap FBXO31 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →