LZTR1
Chr 22ADARleucine zipper like post translational regulator 1
Also known as: BTBD29, LZTR-1, NS10, NS2, SWNTS2
The protein functions as a substrate-specific adapter of an E3 ubiquitin ligase complex that targets Ras proteins for degradation, acting as a negative regulator of RAS-MAPK signaling by controlling Ras levels and membrane association. Mutations cause Noonan syndrome (types 2 and 10) and predispose to schwannomatosis-2, following both autosomal dominant and autosomal recessive inheritance patterns. The gene shows extremely high constraint against loss-of-function variants, indicating that such mutations are typically not tolerated.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.
Literature Evidence
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
500 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 | 64 | 0 | 11 | 0 | 75 |
Likely Pathogenic | 14 | 2 | 1 | 0 | 17 |
VUS | 9 | 207 | 46 | 4 | 266 |
Likely Benign | 0 | 0 | 62 | 62 | 124 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 3 | |||
| Total | 87 | 209 | 120 | 66 | 485 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LZTR1 · 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
External Resources
Links to major genomics databases and tools