FBXO44

Chr 1

F-box protein 44

Also known as: FBG3, FBX30, FBX6A, Fbx44, Fbxo6a

NCBI Gene: 93611 ENSG00000132879 UniProt: Q9H4M3 OMIM: 609111

FBXO44 encodes a substrate-recognition component of E3 ubiquitin ligase complexes that targets specific proteins including BRCA1 and RGS2 for ubiquitination and degradation. The gene is extremely intolerant to loss-of-function variants (pLI near 1.0), suggesting mutations would likely cause severe developmental consequences. Currently, no specific pediatric neurological disorders have been definitively associated with FBXO44 mutations in clinical databases.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. It is also a member of the NFB42 (neural F Box 42 kDa) family, similar to F-box only protein 2 and F-box only protein 6. Several alternatively spliced transcript variants encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.14

Clinical Summary— FBXO44

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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

43 VUS of 77 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?

1.14LOEUF

pLI 0.000

Z-score 1.16

OE 0.69 (0.43–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.92 (0.81–1.05)

159 obs / 172.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.43–1.14)

0≤0.351.4

Missense OE?0.92 (0.81–1.05)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 11 / 16.0Missense obs/exp: 159 / 172.0Syn Z: -0.11

This gene — mechanism propensity

0.6163th %ile

GOF

0.6736th %ile

LOF

0.2680th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

77 submitted variants in ClinVar

ClinVar

Classification Summary

VUS43

Likely Benign23

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	43	43
Likely Benign	23	23
Benign	0	0
Total	66	66

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 53) ClinVar copy-number / structural variants overlap FBXO44 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →