LZTR1

leucine zipper like post translational regulator 1, the group of BTB domain containing

Basic information

Region (hg38): 22:20982269-20999032

Links

ENSG00000099949NCBI:8216OMIM:600574HGNC:6742Uniprot:Q8N653AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Noonan syndrome 10 (Definitive), mode of inheritance: AD
  • Noonan syndrome 2 (Strong), mode of inheritance: AR
  • Noonan syndrome 2 (Moderate), mode of inheritance: AR
  • Noonan syndrome 10 (Definitive), mode of inheritance: AD
  • LZTR1-related schwannomatosis (Definitive), mode of inheritance: AD
  • Noonan syndrome 10 (Strong), mode of inheritance: AD
  • LZTR1-related schwannomatosis (Strong), mode of inheritance: AD
  • Noonan syndrome 2 (Strong), mode of inheritance: AR
  • Noonan syndrome (Supportive), mode of inheritance: AD
  • Noonan syndrome 10 (Strong), mode of inheritance: AD
  • LZTR1-related schwannomatosis (Strong), mode of inheritance: AD
  • Noonan syndrome (Definitive), mode of inheritance: AD
  • Noonan syndrome (Strong), mode of inheritance: AR
  • schwannomatosis (Definitive), mode of inheritance: AD
  • breast cancer (Moderate), mode of inheritance: AD
  • Noonan syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Schwannomatosis 2; Noonan syndrome 10; Noonan syndrome 2AD/ARCardiovascular; Hematologic; OncologicIndividuals with Schwannomatosis are susceptible to schwannomas, and knowledge may allow early management; Individuals with Noonan syndrome may benefit from surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis or hypertrophic cardiomyopathy); Noonan syndrome can can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial; Noonan syndrome can also include schwannomatosis as well as predisposition to other types of cancer, and knowledge may allow early managementCardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic24362817; 25480913; 25795793; 29469822; 30368668

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LZTR1 gene.

  • not provided (197 variants)
  • Cardiovascular phenotype;Hereditary cancer-predisposing syndrome (150 variants)
  • Hereditary cancer-predisposing syndrome;Cardiovascular phenotype (54 variants)
  • LZTR1-related schwannomatosis (10 variants)
  • Noonan syndrome 2 (9 variants)
  • Schwannomatosis (6 variants)
  • Noonan syndrome 10 (4 variants)
  • LZTR1-related disorder (4 variants)
  • Emery-Dreifuss muscular dystrophy (1 variants)
  • Noonan syndrome 2;Noonan syndrome 10 (1 variants)
  • See cases (1 variants)
  • Noonan syndrome 10;Noonan syndrome 2;LZTR1-related schwannomatosis (1 variants)
  • Noonan syndrome 2;Schwannomatosis (1 variants)
  • Noonan syndrome 2;LZTR1-related schwannomatosis;Noonan syndrome 10 (1 variants)
  • Male infertility with azoospermia or oligozoospermia due to single gene mutation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LZTR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
13
clinvar
581
clinvar
8
clinvar
602
missense
3
clinvar
24
clinvar
1528
clinvar
14
clinvar
1569
nonsense
108
clinvar
43
clinvar
7
clinvar
158
start loss
1
clinvar
1
clinvar
2
frameshift
208
clinvar
72
clinvar
18
clinvar
298
inframe indel
1
clinvar
41
clinvar
42
splice donor/acceptor (+/-2bp)
13
clinvar
102
clinvar
17
clinvar
1
clinvar
133
splice region
9
109
73
1
192
non coding
12
clinvar
62
clinvar
226
clinvar
57
clinvar
357
Total 334 253 1687 822 65

Highest pathogenic variant AF is 0.000171

Variants in LZTR1

This is a list of pathogenic ClinVar variants found in the LZTR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
22-20982334-T-A Noonan syndrome 2 • Cardiovascular phenotype;Hereditary cancer-predisposing syndrome • Noonan syndrome 2;Noonan syndrome 10 • LZTR1-related schwannomatosis;Noonan syndrome 2;Noonan syndrome 10 • LZTR1-related schwannomatosis Conflicting classifications of pathogenicity (Sep 12, 2023)549752
22-20982361-G-A not specified Benign/Likely benign (May 28, 2020)389662
22-20982366-C-T not specified • Noonan syndrome and Noonan-related syndrome • LZTR1-related disorder Benign (Feb 04, 2021)928479
22-20982367-C-T Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Uncertain significance (Dec 29, 2022)2453189
22-20982368-C-T Hereditary cancer-predisposing syndrome;Cardiovascular phenotype Conflicting classifications of pathogenicity (Dec 13, 2023)561803
22-20982369-G-A Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Uncertain significance (Oct 29, 2020)1736902
22-20982370-G-A Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Uncertain significance (Aug 28, 2023)3238268
22-20982372-A-G Hereditary cancer-predisposing syndrome;Cardiovascular phenotype Conflicting classifications of pathogenicity (Jun 25, 2021)1403744
22-20982374-G-A Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Pathogenic (May 12, 2023)3238279
22-20982374-G-T Uncertain significance (Mar 08, 2022)1515988
22-20982376-C-G Hereditary cancer-predisposing syndrome;Cardiovascular phenotype Uncertain significance (Dec 29, 2021)1750982
22-20982376-C-T Uncertain significance (Nov 03, 2021)1319820
22-20982375-G-GCTGGACC Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Pathogenic (Jul 30, 2024)2456291
22-20982378-G-A Uncertain significance (Nov 14, 2021)1437042
22-20982380-A-AC Schwannomatosis Pathogenic (Aug 26, 2024)918099
22-20982382-C-A Cardiovascular phenotype;Hereditary cancer-predisposing syndrome • not specified Uncertain significance (Jan 15, 2025)1747014
22-20982382-C-T Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Uncertain significance (Jun 30, 2023)3238031
22-20982382-CGGGCAGCACGGGG-C LZTR1-related schwannomatosis Likely pathogenic (Aug 21, 2023)2676395
22-20982383-G-A Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Likely benign (Aug 21, 2019)1769365
22-20982383-G-T Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Likely benign (Sep 21, 2024)3541631
22-20982385-G-A Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Uncertain significance (Apr 12, 2024)1773978
22-20982387-A-C Cardiovascular phenotype;Hereditary cancer-predisposing syndrome Uncertain significance (Dec 18, 2023)3238124
22-20982388-G-A Hereditary cancer-predisposing syndrome;Cardiovascular phenotype Conflicting classifications of pathogenicity (Nov 10, 2024)1780366
22-20982388-G-C Uncertain significance (May 20, 2024)2143922
22-20982388-G-T Hereditary cancer-predisposing syndrome;Cardiovascular phenotype Uncertain significance (Aug 22, 2024)2433579

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
LZTR1protein_codingprotein_codingENST00000215739 2119577
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.02e-929.60e-2512536203861257480.00154
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5775035410.9300.00003515428
Missense in Polyphen163202.820.803682073
Synonymous-0.9072562381.070.00001701622
Loss of Function-8.0510546.02.280.00000232485

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002920.00291
Ashkenazi Jewish0.0007320.000695
East Asian0.001800.00180
Finnish0.004030.00389
European (Non-Finnish)0.001140.00113
Middle Eastern0.001800.00180
South Asian0.001580.00157
Other0.002520.00245

dbNSFP

Source: dbNSFP

Function
FUNCTION: Probable transcriptional regulator that may play a crucial role in embryogenesis.;
Disease
DISEASE: Schwannomatosis 2 (SWNTS2) [MIM:615670]: A cancer predisposition syndrome in which patients develop multiple non- vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269|PubMed:24362817}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Noonan syndrome 10 (NS10) [MIM:616564]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. {ECO:0000269|PubMed:25795793}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.101

Intolerance Scores

loftool
0.982
rvis_EVS
-2.68
rvis_percentile_EVS
0.73

Haploinsufficiency Scores

pHI
0.218
hipred
N
hipred_score
0.411
ghis
0.621

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Lztr1
Phenotype
homeostasis/metabolism phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process
regulation of transcription, DNA-templated;anatomical structure morphogenesis
Cellular component
Golgi apparatus
Molecular function
DNA-binding transcription factor activity