GeneBe

LZTR1

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

Basic information

Region (hg38): 22:20982269-20999032

Links

ENSG00000099949 ∙ NCBI:8216 ∙ OMIM:600574 ∙ HGNC:6742 ∙ Uniprot:Q8N653 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Noonan syndrome 10 (Definitive), mode of inheritance: AD
  • Noonan syndrome 2 (Strong), mode of inheritance: AR
  • Noonan syndrome 10 (Definitive), mode of inheritance: AD
  • 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 10 (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.

  • Cardiovascular_phenotype (2889 variants)
  • Hereditary_cancer-predisposing_syndrome (2889 variants)
  • not_provided (2762 variants)
  • LZTR1-related_schwannomatosis (443 variants)
  • not_specified (251 variants)
  • Noonan_syndrome_10 (187 variants)
  • Noonan_syndrome_2 (166 variants)
  • LZTR1-related_disorder (138 variants)
  • Noonan_syndrome_and_Noonan-related_syndrome (41 variants)
  • RASopathy (27 variants)
  • Schwannomatosis (25 variants)
  • Noonan_syndrome (15 variants)
  • Noonan_syndrome_1 (9 variants)
  • See_cases (4 variants)
  • Diffuse_midline_glioma,_H3_K27-altered (3 variants)
  • Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (3 variants)
  • Bladder_exstrophy (2 variants)
  • Short_stature (2 variants)
  • Hereditary_breast_ovarian_cancer_syndrome (2 variants)
  • Autism_spectrum_disorder (1 variants)
  • Familial_multiple_meningioma (1 variants)
  • Intellectual_disability (1 variants)
  • Inborn_genetic_diseases (1 variants)
  • LZTR1-associated_CaLMs-syndrome (1 variants)
  • Primary_dilated_cardiomyopathy (1 variants)
  • Congenital_diaphragmatic_hernia (1 variants)
  • Pigmentary_skin_disorders (1 variants)
  • Hypertrophic_cardiomyopathy_1 (1 variants)
  • Non-immune_hydrops_fetalis (1 variants)
  • Emery-Dreifuss_muscular_dystrophy (1 variants)
  • Fetal_cystic_hygroma (1 variants)
  • Hereditary_cancer (1 variants)
  • Pediatric_high-grade_glioma (1 variants)
  • Developmental_disorder (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. These statistics are base on transcript: NM_000006767.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
4
clinvar
33
clinvar
715
clinvar
6
clinvar
 763
missense
12
clinvar
75
clinvar
1845
clinvar
70
clinvar
 2002
nonsense
139
clinvar
50
clinvar
8
clinvar
 197
start loss
1
1
1
 3
frameshift
288
clinvar
90
clinvar
18
clinvar
 396
splice donor/acceptor (+/-2bp)
9
clinvar
153
clinvar
14
clinvar
 176
Total 454 373 1919 785 6

Highest pathogenic variant AF is 0.00009299442

Loading clinvar variants...

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