LZTR1 Gene: Leucine Zipper Like Transcription Regulator 1
A key regulator of RAS/MAPK signaling and tumor suppression, implicated in Noonan syndrome and glioblastoma.
Gene Information Card
| Symbol | LZTR1 |
|---|---|
| Full Name | Leucine Zipper Like Transcription Regulator 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 8216 ncbi.nlm.nih.gov/gene/8216 |
| Ensembl ID | ENSG00000100029 |
| UniProt ID | Q8N653 |
| OMIM ID | 600574 |
| HGNC ID | 6747 |
| Aliases | BTBD29, LZTR-1, SWNTS2 |
Description
LZTR1 encodes a protein containing BTB/POZ and Kelch domains, acting as a substrate adaptor for the CUL3 ubiquitin ligase complex. It negatively regulates the RAS/MAPK signaling pathway by promoting ubiquitination and degradation of RAS proteins. Loss-of-function mutations lead to RAS pathway hyperactivation, contributing to developmental disorders (Noonan syndrome) and tumorigenesis (glioblastoma, schwannomatosis).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Noonan syndrome | Loss-of-function mutations impair RAS degradation, leading to increased RAS-MAPK signaling during development. | ClinVar, OMIM #600574 |
| Schwannomatosis 2 | Germline LZTR1 mutations predispose to multiple schwannomas via RAS pathway dysregulation. | OMIM #615670, ClinVar |
| Glioblastoma | Somatic mutations and deletions of LZTR1 are recurrent in glioblastoma, promoting tumor growth. | COSMIC, NCBI Gene |
| RASopathies | LZTR1 alterations contribute to a spectrum of disorders with overlapping features of Noonan syndrome. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Heart | 3.8 | Low |
| Lung | 2.1 | Low |
| Liver | 1.5 | Low |
| Kidney | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 4.5 | Embryonic kidney cell line |
| SH-SY5Y | 6.1 | Neuroblastoma cell line |
| U87MG | 3.2 | Glioblastoma cell line |
| HeLa | 2.8 | Cervical carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.742C>T (p.Arg248*) | Nonsense | <0.1% in general population | Loss of function; truncation of Kelch domain |
| c.517G>A (p.Gly173Arg) | Missense | Rare in Noonan syndrome | Impaired substrate binding; dominant negative effect |
| c.1285C>T (p.Arg429Cys) | Missense | Somatic in glioblastoma | Reduced ubiquitin ligase activity |
| Deletion of 22q11.21 | Copy number loss | Recurrent in glioblastoma | Complete loss of LZTR1 expression |
Mutation functional classification
Loss of Function (LOF)
Most common mechanism; nonsense, frameshift, or splice-site mutations lead to truncated or absent protein, reducing RAS ubiquitination and increasing MAPK signaling.
Gain of Function (GOF)
Not well documented; some missense variants may alter substrate specificity but evidence is limited.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly173Arg) can interfere with wild-type LZTR1 function, impairing CUL3 complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin ligase complex | • protein ubiquitination |
| • negative regulation of Ras protein signal transduction | • BTB domain binding |
| • Kelch repeat binding |
Pathways
• RAS/MAPK signaling
• CUL3-mediated ubiquitination
• Receptor tyrosine kinase signaling
Protein Summary
The LZTR1 protein (UniProt Q8N653) contains an N-terminal BTB/POZ domain and six C-terminal Kelch repeats. It functions as a substrate adaptor for the CUL3-RING E3 ubiquitin ligase complex, targeting RAS proteins for proteasomal degradation. This regulation is critical for controlling cell proliferation and differentiation. Mutations that disrupt LZTR1 function lead to RAS pathway hyperactivation, contributing to developmental syndromes and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LZTR1 Knockout HEK293 Cell Line | EDJ-KQ2904 | Human | 8216 | Details Get a Quote |
| LZTR1 Knockout A-549 Cell Line | EDJ-KQ23986 | Human | 8216 | Details Get a Quote |
| LZTR1 Knockout HCT 116 Cell Line | EDJ-KQ23987 | Human | 8216 | Details Get a Quote |
| LZTR1 Knockout HeLa Cell Line | EDJ-KQ23988 | Human | 8216 | Details Get a Quote |
