FBH1

Chr 10AD

F-box DNA helicase 1

Also known as: FBXO18, Fbx18, hFBH1

This protein functions as a 3'-5' DNA helicase that maintains genome stability by regulating DNA replication fork processing and homologous recombination, and also serves as a component of an E3 ubiquitin ligase complex. Mutations cause autosomal dominant early-onset epilepsy with or without developmental delay, neurodevelopmental disorder with speech impairment and dysmorphic features, or hypocalciuric hypercalcemia. The gene is highly constrained against loss-of-function variants (LOEUF 0.479), indicating that such variants are likely pathogenic.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 2, with or without developmental delayMIM #618832
AD
Neurodevelopmental disorder with speech impairment and dysmorphic faciesMIM #619056
AD
Hypocalciuric hypercalcemia, type IMIM #145980
AD
0
Active trials
4
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.48
LOEUF
Mechanism
Clinical SummaryFBH1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.000
Z-score 4.69
OE 0.32 (0.220.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.82Z-score
OE missense 0.69 (0.640.75)
453 obs / 656.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.32 (0.220.48)
00.351.4
Missense OE0.69 (0.640.75)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 18 / 55.8Missense obs/exp: 453 / 656.4Syn Z: 0.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FBH1 · 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 →