LZTS1

protein-coding

leucine zipper tumor suppressor 1, the group of Leucine zipper tumor suppressor family

Gene summary

This gene encodes a tumor suppressor protein that is ubiquitously expressed in normal tissues. In uveal melanomas, expression of this protein is silenced in rapidly metastasizing and metastatic tumor cells but has normal expression in slowly metastasizing or nonmetastasizing tumor cells. This protein may have a role in cell-cycle control by interacting with the Cdk1/cyclinB1 complex. This gene is located on chromosomal region 8p22. Loss of heterozygosity (LOH) in the 8p arm is a common characteristic of many types of cancer. [provided by RefSeq, Nov 2009]

MANE transcript

NM_021020.5

Inheritance

—

ClinVar variants

P:2U:262B:163

Top phenotype

LZTS1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr8:20,246,165-20,303,963

External References & Databases

Ensembl (ENSG00000061337)

Transcript & Mutation Effects

hg38 • Region Span ~57.8 kb

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GenCC 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 LZTS1 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 420

not specifiedTotal: 95

LZTS1-related disorderTotal: 33

Esophageal squamous cell carcinoma, somaticTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021020.5. 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				131 clinvar	8 clinvar	139
missense	2 clinvar		255 clinvar	18 clinvar	6 clinvar	281
nonsense			2 clinvar			2
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	2	0	262	149	14	427

Highest pathogenic variant AF is 7.670535e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021020.5	RefSeq	NP_066300.1	3	MANE Select
ENST00000381569.5	Ensembl	ENSP00000370981.1	3	MANE Select
NM_001362884.2	RefSeq	NP_001349813.1	3	Standard
ENST00000265801.6	Ensembl	ENSP00000265801.6	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

transcription, DNA-templated
regulation of transcription, DNA-templated
negative regulation of macroautophagy
mitotic cell cycle phase transition

Molecular Function

DNA binding
DNA-binding transcription factor activity
protein binding
microtubule binding

Cellular Component

cytoplasm
postsynaptic density
cell junction
dendritic spine
postsynaptic membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381569
Coding exons: 3
Length: 57799
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125746
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.217	359	371	0.968	0.0000256	3831
Missense (PolyPhen)		119	136.68	0.87064		1502
Synonymous	0.100	174	176	0.990	0.0000125	1217
Loss of Function	3.56	2	18.5	0.108	7.99e-7	225

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}.;
Disease: DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. {ECO:0000269|PubMed:10097140}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.219

Intolerance Scores

LoFtool: 0.118
RVIS EVS: 0.4
RVIS percentile EVS: 76.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium