LZTS2
protein-codingleucine zipper tumor suppressor 2, the group of Leucine zipper tumor suppressor family
Gene summary
The protein encoded by this gene belongs to the leucine zipper tumor suppressor family of proteins, which function in transcription regulation and cell cycle control. This family member can repress beta-catenin-mediated transcriptional activation and is a negative regulator of the Wnt signaling pathway. It negatively regulates microtubule severing at centrosomes, and is necessary for central spindle formation and cytokinesis completion. It is implicated in cancer, where it may inhibit cell proliferation and decrease susceptibility to tumor development. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LZTS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001318100.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 3 | 1 | 6 | ||
| missense | 147 | 1 | 148 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 149 | 4 | 1 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001305029.1 | 4 | MANE Select | |
| Ensembl | ENSP00000416972.2 | 4 | MANE Select | |
| RefSeq | NP_001305028.1 | 4 | Standard | |
| RefSeq | NP_001305030.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lzts2a | Danio rerio | Structure: head Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mitotic cytokinesis
- kidney development
- negative regulation of cell population proliferation
- Wnt signaling pathway
- microtubule severing
Molecular Function
- protein binding
Cellular Component
- centrosome
- cytosol
- microtubule
- plasma membrane
- midbody
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370220
- Coding exons
- 4
- Length
- 11219
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125742
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.735 | 371 | 413 | 0.898 | 0.0000283 | 4170 |
| Missense (PolyPhen) | 88 | 112.11 | 0.78498 | 1112 | ||
| Synonymous | 0.264 | 171 | 175 | 0.975 | 0.0000105 | 1532 |
| Loss of Function | 3.58 | 8 | 28.7 | 0.279 | 0.00000210 | 241 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000092 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000058 | 0.000046 | rare |
| European (Non-Finnish) | 0.000084 | 0.000070 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negative regulator of katanin-mediated microtubule severing and release from the centrosome. Required for central spindle formation and the completion of cytokinesis. May negatively regulate axonal outgrowth by preventing the formation of microtubule bundles that are necessary for transport within the elongating axon. Negative regulator of the Wnt signaling pathway. Represses beta-catenin-mediated transcriptional activation by promoting the nuclear exclusion of beta-catenin. {ECO:0000255|HAMAP-Rule:MF_03026, ECO:0000269|PubMed:17000760, ECO:0000269|PubMed:17351128, ECO:0000269|PubMed:17950943, ECO:0000269|PubMed:18490357}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.569
- RVIS EVS
- -1.2
- RVIS percentile EVS
- 5.83
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |