LRRC19
Chr 9leucine rich repeat containing 19
LRRC19 encodes a pathogen-recognition receptor that mediates NF-kappaB signaling pathway activation and induces pro-inflammatory cytokine expression, particularly important for preventing uropathogenic bacterial infections in the kidney and regulating host-microbiota interactions in the gut. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.777), and no established Mendelian disease associations have been reported to date. Clinical significance of LRRC19 variants in pediatric patients remains unclear given the lack of documented disease phenotypes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
154 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 69 | 0 | 69 |
Likely Pathogenic | 0 | 0 | 6 | 0 | 6 |
VUS | 0 | 49 | 14 | 0 | 63 |
Likely Benign | 0 | 8 | 1 | 2 | 11 |
Benign | 1 | 0 | 0 | 0 | 1 |
| Total | 1 | 57 | 90 | 2 | 150 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LRRC19 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools