FBXL19

Chr 16

F-box and leucine rich repeat protein 19

Also known as: CXXC11, Fbl19, JHDM1C

The protein functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes, mediating ubiquitination and degradation of multiple targets including RHOA, RAC1, RAC3, and IL1RL1, while also recruiting factors for chromatin regulation and gene expression during cell differentiation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.10
Clinical SummaryFBXL19
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 5.05
OE 0.00 (0.000.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.87Z-score
OE missense 0.46 (0.410.52)
189 obs / 409.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.10)
00.351.4
Missense OE0.46 (0.410.52)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 0 / 29.7Missense obs/exp: 189 / 409.3Syn Z: 0.03
DN
0.2199th %ile
GOF
0.3491th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.10

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FBXL19 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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