FBXL19

Chr 16

F-box and leucine rich repeat protein 19

Also known as: CXXC11, Fbl19, JHDM1C

NCBI Gene: 54620ENSG00000099364UniProt: Q6PCT2

This gene encodes a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases. The encoded protein is reported to bind to the transmembrane receptor interleukin 1 receptor-like 1 and regulate its ubiquitination and degradation. This protein has been linked to the regulation of pulmonary inflammation and psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

98
ClinVar variants
14
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FBXL19
⚡
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.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 79 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.10LOEUF
pLI 1.000
Z-score 5.05
OE 0.00 (0.00–0.10)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.87Z-score
OE missense 0.46 (0.41–0.52)
189 obs / 409.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.46 (0.41–0.52)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 0 / 29.7Missense obs/exp: 189 / 409.3Syn Z: 0.03

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS79
Likely Benign2
Benign3
11
Pathogenic
3
Likely Pathogenic
79
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
3
0
3
VUS
3
68
8
0
79
Likely Benign
0
0
0
2
2
Benign
0
1
0
2
3
Total36922498

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics of psoriatic arthritis.
O'Rielly DD et al.·Best Pract Res Clin Rheumatol
2014Review
The pathogenesis and genetics of psoriasis.
Puig L et al.·Actas Dermosifiliogr
2014Review
Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans.
Kimbrel NA et al.·JAMA Psychiatry
2023Meta-analysis
LncRNA FBXL19-AS1 promotes breast cancer cells proliferation and invasion via acting as a molecular sponge to miR-718.
Ding Z et al.·Biosci Rep
2019
Ubiquitin-Proteasome System in Periodontitis: Mechanisms and Clinical Implications.
Ma Y et al.·Cell Prolif
2025Review
Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program.
Ashley-Koch AE et al.·PLoS Genet
2023Meta-analysis
lncRNA FBXL19-AS1 is a diagnosis biomarker for paediatric patients with acute myeloid leukemia.
Sheng H et al.·J Gene Med
2021Cohort
Paradoxical Psoriasis in Patients Receiving Therapy with Tumor Necrosis Factor Inhibitors: Potential Pathogenic Mechanisms and the Role of Genetic Factors.
Costin D et al.·Int J Mol Sci
2024Review
F-box protein complex FBXL19 regulates TGFβ1-induced E-cadherin down-regulation by mediating Rac3 ubiquitination and degradation.
Dong S et al.·Mol Cancer
2014
Role of alternative splicing signatures in the prognosis of glioblastoma.
Xie ZC et al.·Cancer Med
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Unveiling EXOC4/SEC8: a key player in enhancing antiviral immunity by inhibiting the FBXL19-STING1-SQSTM1 signaling axis.
Wang L et al.·Autophagy
2025
FBXL19 in endothelial cells protects the heart from influenza A infection by enhancing antiviral immunity and reducing cellular senescence programs.
Xia B et al.·Am J Physiol Heart Circ Physiol
2024
Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants.
Assarsson M et al.·Acta Derm Venereol
2024🔓 Open AccessCohort
Exploring the regulatory role of FBXL19-AS1 in triple-negative breast cancer through the miR-378a-3p/OTUB2 axis.
Guo C et al.·Cell Biochem Funct
2024
FBXL19 Targeted STK11 Degradation Enhances Cigarette Smoke-Induced Airway Epithelial Cell Cytotoxicity.
Li X et al.·COPD
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools