LZTFL1 Gene

Name	leucine zipper transcription factor-like 1
Description	This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. [provided by RefSeq, Aug 2020]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leucine zipper transcription factor–like 1 (LZTFL1) is a multifunctional protein encoded within a 3p21.3 hotspot that has emerged as an important regulator in both ciliary signaling and cellular differentiation. In the primary cilium, LZTFL1 interacts with the Bardet–Biedl syndrome (BBS) complex (BBSome) to control the trafficking and removal of key signaling receptors—including Smoothened and Patched‐1—thereby modulating Hedgehog signal transduction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Loss of LZTFL1 function, as observed in patients with Bardet–Biedl syndrome (BBS17), results in aberrant ciliary protein localization and overactivation of Sonic Hedgehog signaling, contributing to developmental abnormalities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, LZTFL1 functions as a tumor suppressor by maintaining epithelial cell differentiation and inhibiting epithelial-to-mesenchymal transition (EMT). Downregulation of LZTFL1—whether directly or via its repression by oncomiRs such as miR-21—facilitates nuclear translocation of β-catenin and activation of pro-metastatic pathways in cancers of the breast, lung, and stomach."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in ciliogenesis and tumor suppression, LZTFL1 contributes to immune regulation and energy homeostasis. In T cells, retinoic acid–induced increases in LZTFL1 expression modulate T cell activation and cytokine production, highlighting a role in adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In the central nervous system, LZTFL1 is implicated in leptin receptor signaling in the hypothalamus, influencing food intake, energy expenditure, and obesity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Furthermore, LZTFL1 suppression by long noncoding RNAs in hepatocellular carcinoma underscores its involvement in posttranscriptional regulatory networks that favor tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, genetic variants that increase LZTFL1 expression have been linked to a heightened risk of severe COVID-19, possibly through the modulation of airway epithelial cell differentiation and EMT-related antiviral responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these findings indicate that LZTFL1 is pivotal for proper ciliary function and signal transduction, while also acting as a tumor suppressor and a modulator of immune and metabolic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thibaut Eguether, Jovenal T San Agustin, Brian T Keady, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IFT27 links the BBSome to IFT for maintenance of the ciliary signaling compartment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2014.09.011"}], "href": "https://doi.org/10.1016/j.devcel.2014.09.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25446516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25446516"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Seongjin Seo, Qihong Zhang, Kevin Bugge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002358"}], "href": "https://doi.org/10.1371/journal.pgen.1002358"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22072986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22072986"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sophie Scheidecker, Christelle Etard, Nathan W Pierce, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2013-101785"}], "href": "https://doi.org/10.1136/jmedgenet-2013-101785"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24026985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24026985"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jiangsong Jiang, Kanyarat Promchan, Hong Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Depletion of BBS Protein LZTFL1 Affects Growth and Causes Retinal Degeneration in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Genet Genomics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jgg.2015.11.006"}], "href": "https://doi.org/10.1016/j.jgg.2015.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27312011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27312011"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hui Wang, Zheqiong Tan, Hui Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12885-019-5951-3"}], "href": "https://doi.org/10.1186/s12885-019-5951-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31351450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31351450"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Q Wei, Z-H Chen, L Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.328"}], "href": "https://doi.org/10.1038/onc.2015.328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26364604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26364604"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qun Wei, Wen Zhou, Weining Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-suppressive functions of leucine zipper transcription factor-like 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-3826"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-3826"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20233871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20233871"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Linbo Wang, Jufeng Guo, Qinchuan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LZTFL1 suppresses gastric cancer cell migration and invasion through regulating nuclear translocation of β-catenin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-014-1753-9"}], "href": "https://doi.org/10.1007/s00432-014-1753-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25005785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25005785"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hong Jiang, Kanyarat Promchan, Bor-Ruei Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LZTFL1 Upregulated by All-Trans Retinoic Acid during CD4+ T Cell Activation Enhances IL-5 Production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1500719"}], "href": "https://doi.org/10.4049/jimmunol.1500719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26700766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26700766"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Qun Wei, Yi-Feng Gu, Qing-Jun Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lztfl1/BBS17 controls energy homeostasis by regulating the leptin signaling in the hypothalamic neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mjy022"}], "href": "https://doi.org/10.1093/jmcb/mjy022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30423168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30423168"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Haitao Wang, Pei Ma, Pengpeng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA SNHG6 promotes hepatocellular carcinoma progression by interacting with HNRNPL/PTBP1 to facilitate SETD7/LZTFL1 mRNA destabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.07.009"}], "href": "https://doi.org/10.1016/j.canlet.2021.07.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34252487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34252487"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Damien J Downes, Amy R Cross, Peng Hua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-021-00955-3"}], "href": "https://doi.org/10.1038/s41588-021-00955-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34737427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34737427"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Iris M Fink-Baldauf, William D Stuart, John J Brewington, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRISPRi links COVID-19 GWAS loci to LZTFL1 and RAVER1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2021.103806"}], "href": "https://doi.org/10.1016/j.ebiom.2021.103806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34998241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34998241"}]}]}]}
Synonyms	BBS17
Proteins	LZTL1_HUMAN
NCBI Gene ID	54585
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LZTFL1 has 6,353 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 114 datasets.

Click the + buttons to view associations for LZTFL1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LZTFL1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LZTFL1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LZTFL1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of LZTFL1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LZTFL1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of LZTFL1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LZTFL1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LZTFL1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LZTFL1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LZTFL1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of LZTFL1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LZTFL1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of LZTFL1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LZTFL1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LZTFL1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LZTFL1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LZTFL1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of LZTFL1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with LZTFL1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LZTFL1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of LZTFL1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LZTFL1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LZTFL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LZTFL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LZTFL1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LZTFL1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with LZTFL1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LZTFL1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LZTFL1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LZTFL1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LZTFL1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LZTFL1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving LZTFL1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving LZTFL1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LZTFL1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with LZTFL1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with LZTFL1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with LZTFL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LZTFL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at LZTFL1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LZTFL1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.