LZTFL1

leucine zipper transcription factor like 1

Basic information

Region (hg38): 3:45823315-45916042

Links

ENSG00000163818 ∙ NCBI:54585 ∙ OMIM:606568 ∙ HGNC:6741 ∙ Uniprot:Q9NQ48 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 17 (Moderate), mode of inheritance: AR
• Bardet-Biedl syndrome 17 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 17 (Strong), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 17	AR	Cardiovascular; Endocrine	The condition can involve congenital cardiac anomalies, and awareness may allow early management; Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	17163542; 22510444; 23692385; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LZTFL1 gene.

• not provided (132 variants)
• Bardet-Biedl syndrome 17 (21 variants)
• Inborn genetic diseases (6 variants)
• LZTFL1-related condition (4 variants)
• Bardet-Biedl syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LZTFL1 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			2	23		25
missense			62	4	1	67
nonsense	4	1				5
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)		3				3
splice region			4	4		8
non coding				26		26
Total	7	4	64	53	1

Highest pathogenic variant AF is 0.00000657

Variants in LZTFL1

This is a list of pathogenic ClinVar variants found in the LZTFL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-45826321-T-A			Uncertain significance (May 10, 2022)
3-45826328-C-G		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
3-45826342-T-C			Likely benign (Jun 20, 2022)
3-45827337-C-A			Likely benign (Feb 10, 2021)
3-45827337-C-T		Bardet-Biedl syndrome 17	Likely benign (Feb 24, 2023)
3-45827338-G-A		Bardet-Biedl syndrome 17	Benign/Likely benign (Dec 14, 2023)
3-45827340-G-A		Bardet-Biedl syndrome 17	Benign/Likely benign (Jan 29, 2024)
3-45827370-C-T			Likely benign (Feb 24, 2021)
3-45827394-C-T			Uncertain significance (Jul 21, 2022)
3-45827422-C-T		Bardet-Biedl syndrome 17 • Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
3-45827425-T-C		Bardet-Biedl syndrome 17	Uncertain significance (Mar 24, 2022)
3-45827437-T-C			Uncertain significance (Nov 23, 2019)
3-45827439-C-G		Inborn genetic diseases • LZTFL1-related disorder	Uncertain significance (Jan 08, 2024)
3-45827445-T-C			Likely benign (Jan 13, 2022)
3-45827454-T-C			Likely benign (May 27, 2022)
3-45827459-C-A		Bardet-Biedl syndrome 1 • Bardet-Biedl syndrome 17	Pathogenic (May 01, 2014)
3-45827460-C-T			Likely pathogenic (Jun 13, 2022)
3-45827462-G-A		Bardet-Biedl syndrome 17	Uncertain significance (Jul 21, 2022)
3-45828429-GTCT-G			Likely benign (Dec 13, 2022)
3-45828450-T-C		Bardet-Biedl syndrome 17 • LZTFL1-related disorder	Uncertain significance (Jan 24, 2024)
3-45828474-G-A			Uncertain significance (Jul 06, 2022)
3-45828480-C-T			Benign (Jan 30, 2024)
3-45828481-G-A		LZTFL1-related disorder	Likely benign (Oct 28, 2022)
3-45828490-T-C			Likely benign (Dec 22, 2023)
3-45828492-T-C		LZTFL1-related disorder	Conflicting classifications of pathogenicity (Oct 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LZTFL1	protein_coding	protein_coding	ENST00000296135	10	92727

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0591	0.940	125734	0	13	125747	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	89	145	0.614	0.00000683	1963
Missense in Polyphen		14	35.396	0.39552		541
Synonymous	1.18	42	52.9	0.793	0.00000251	528
Loss of Function	2.98	6	20.6	0.291	0.00000111	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000124
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.000200	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function. {ECO:0000269|PubMed:20233871, ECO:0000269|PubMed:22072986, ECO:0000269|PubMed:22510444}.
• Disease: DISEASE: Bardet-Biedl syndrome 17 (BBS17) [MIM:615994]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:22510444, ECO:0000269|PubMed:23692385}. Note=The disease is caused by mutations affecting the gene represented in this entry. Patients carrying LZTFL1 mutations manifest mesoaxial polydactyly, a clinical feature very uncommon for Bardet-Biedl syndrome (PubMed:22510444 and PubMed:23692385). Some patients manifest situs inversus (PubMed:22510444). {ECO:0000269|PubMed:22510444}.
• Pathway: BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.619
• rvis_EVS: 0.5
• rvis_percentile_EVS: 79.89

Haploinsufficiency Scores

• pHI: 0.115
• hipred: Y
• hipred_score: 0.748
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lztfl1
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: lztfl1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: viability

Gene ontology

• Biological process: negative regulation of protein localization to cilium;negative regulation of protein localization to ciliary membrane
• Cellular component: cytosol
• Molecular function: protein binding;identical protein binding;protein-containing complex binding