FBXO31

Chr 16AR

F-box protein 31

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

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.

Summary from RefSeq, OMIM, UniProt

Primary Disease Associations & Inheritance

?Intellectual developmental disorder, autosomal recessive 45MIM #615979
AR
0
Active trials
8
Pubs (1 yr)
59
P/LP submissions
2%
P/LP missense
0.46
LOEUF
Mechanism
Clinical SummaryFBXO31
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 97 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.444
Z-score 3.48
OE 0.22 (0.110.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.46Z-score
OE missense 0.63 (0.560.70)
214 obs / 342.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.110.46)
00.351.4
Missense OE0.63 (0.560.70)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 5 / 23.0Missense obs/exp: 214 / 342.0Syn Z: -0.44

ClinVar Variant Classifications

199 submitted variants in ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic11
VUS97
Likely Benign24
Benign5
43
Pathogenic
11
Likely Pathogenic
97
VUS
24
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
42
0
43
Likely Pathogenic
1
1
9
0
11
VUS
0
75
19
3
97
Likely Benign
0
3
1
20
24
Benign
0
0
2
3
5
Total2797326180

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXO31 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC