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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schwannomatosis 2; Noonan syndrome 10; Noonan syndrome 2	AD/AR	Cardiovascular; Hematologic; Oncologic	Individuals 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 management	Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic	24362817; 25480913; 25795793; 29469822; 30368668

ClinVar

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

• not provided (182 variants)
• Cardiovascular phenotype;Hereditary cancer-predisposing syndrome (121 variants)
• Hereditary cancer-predisposing syndrome;Cardiovascular phenotype (45 variants)
• Schwannomatosis 2 (12 variants)
• Noonan syndrome 2 (6 variants)
• Noonan syndrome 10 (5 variants)
• LZTR1-related disorder (5 variants)
• Emery-Dreifuss muscular dystrophy (1 variants)
• Schwannomatosis;Noonan syndrome 2 (1 variants)
• Noonan syndrome 10;Noonan syndrome 2 (1 variants)
• Noonan syndrome (1 variants)
• Schwannomatosis (1 variants)
• Schwannomatosis 2;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			12	549	7	568
missense	3	21	1386	9		1419
nonsense	95	35	7			137
start loss	1		1			2
frameshift	179	65	21			265
inframe indel			32			32
splice donor/acceptor (+/-2bp)	12	98	9			119
splice region		5	108	73	1	187
non coding		2	50	217	54	323
Total	290	221	1518	775	61

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 • Noonan syndrome 2;Noonan syndrome 10 • LZTR1-related schwannomatosis;Noonan syndrome 2;Noonan syndrome 10 • Hereditary cancer-predisposing syndrome;Cardiovascular phenotype • LZTR1-related schwannomatosis	Conflicting classifications of pathogenicity (Sep 12, 2023)
22-20982361-G-A		not specified	Benign/Likely benign (May 28, 2020)
22-20982366-C-T		not specified • Noonan syndrome and Noonan-related syndrome • LZTR1-related disorder	Benign (Feb 04, 2021)
22-20982367-C-T		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Uncertain significance (Dec 29, 2022)
22-20982368-C-T		Hereditary cancer-predisposing syndrome;Cardiovascular phenotype	Conflicting classifications of pathogenicity (Dec 13, 2023)
22-20982369-G-A		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Uncertain significance (Oct 29, 2020)
22-20982370-G-A		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Uncertain significance (Aug 28, 2023)
22-20982372-A-G		Hereditary cancer-predisposing syndrome;Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jun 25, 2021)
22-20982374-G-A		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Pathogenic (May 12, 2023)
22-20982374-G-T			Uncertain significance (Mar 08, 2022)
22-20982376-C-G		Hereditary cancer-predisposing syndrome;Cardiovascular phenotype	Uncertain significance (Dec 29, 2021)
22-20982376-C-T			Uncertain significance (Nov 03, 2021)
22-20982375-G-GCTGGACC		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Pathogenic (Dec 29, 2023)
22-20982378-G-A			Uncertain significance (Nov 14, 2021)
22-20982380-A-AC		Schwannomatosis	Pathogenic (Aug 26, 2024)
22-20982382-C-A		Hereditary cancer-predisposing syndrome;Cardiovascular phenotype	Uncertain significance (Feb 18, 2022)
22-20982382-C-T		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 30, 2023)
22-20982382-CGGGCAGCACGGGG-C		LZTR1-related schwannomatosis	Likely pathogenic (Aug 21, 2023)
22-20982383-G-A		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Likely benign (Aug 21, 2019)
22-20982385-G-A		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Uncertain significance (Jul 19, 2021)
22-20982387-A-C		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Uncertain significance (Dec 18, 2023)
22-20982388-G-A		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Likely benign (Mar 05, 2024)
22-20982388-G-C			Uncertain significance (Dec 07, 2022)
22-20982388-G-T			Uncertain significance (Dec 30, 2020)
22-20982389-CA-C		Cardiovascular phenotype;Hereditary cancer-predisposing syndrome	Pathogenic (Nov 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LZTR1	protein_coding	protein_coding	ENST00000215739	21	19577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.02e-92	9.60e-25	125362	0	386	125748	0.00154

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.577	503	541	0.930	0.0000351	5428
Missense in Polyphen		163	202.82	0.80368		2073
Synonymous	-0.907	256	238	1.07	0.0000170	1622
Loss of Function	-8.05	105	46.0	2.28	0.00000232	485

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00292	0.00291
Ashkenazi Jewish	0.000732	0.000695
East Asian	0.00180	0.00180
Finnish	0.00403	0.00389
European (Non-Finnish)	0.00114	0.00113
Middle Eastern	0.00180	0.00180
South Asian	0.00158	0.00157
Other	0.00252	0.00245

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

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

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