SZT2 Gene

Name	seizure threshold 2 homolog (mouse)
Description	The protein encoded by this gene is expressed in the brain, predominantly in the parietal and frontal cortex as well as in dorsal root ganglia. It is localized to the peroxisome, and is implicated in resistance to oxidative stress. It likely functions by increasing superoxide dismutase (SOD) activity, but itself has no direct SOD activity. Studies in mice show that this gene confers low seizure threshold, and may also enhance epileptogenesis. [provided by RefSeq, Jun 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSZT2 functions as a key regulator of nutrient sensing by acting as an essential component of lysosome‐associated protein complexes. In particular, SZT2 integrates into the KICSTOR complex and, together with its partners, orchestrates the recruitment and function of GATOR1 (and in conjunction with GATOR2 within a SOG complex) to negatively regulate mTORC1 signaling during amino acid or glucose deprivation. Loss of SZT2 function results in aberrant, constitutive mTORC1 activation—with increased downstream phosphorylation responses observed in multiple tissues including the brain—thereby underscoring its pivotal role in metabolic adaptation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn clinical settings, mutations in SZT2 are associated with a broad spectrum of neurodevelopmental disorders. Patients with biallelic SZT2 mutations commonly exhibit early‐onset epileptic encephalopathy characterized by refractory seizures, intellectual disability, and distinctive neuroanatomical anomalies such as macrocephaly, corpus callosum malformations, and impaired myelination. These findings indicate that SZT2 is critical not only for nutrient regulation but also for modulating neuronal excitability and seizure threshold, with phenotypic variability reflecting differences in the residual activity of the protein."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the establishment of patient‐derived induced pluripotent stem cell models harboring SZT2 mutations is paving the way for in‐depth investigations into the molecular mechanisms underlying SZT2 deficiency. These innovative cellular platforms, in combination with comprehensive interactome analyses, are expected to shed light on additional roles of SZT2—including potential involvement in autophagy and ciliogenesis—and ultimately accelerate the development of targeted therapeutic strategies for SZT2‐related epileptic and intellectual disability disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rachel L Wolfson, Lynne Chantranupong, Gregory A Wyant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21423"}], "href": "https://doi.org/10.1038/nature21423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28199306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28199306"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Min Peng, Na Yin, Ming O Li "}, {"type": "b", "children": [{"type": "t", "text": "SZT2 dictates GATOR control of mTORC1 signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21378"}], "href": "https://doi.org/10.1038/nature21378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28199315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28199315"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuji Nakamura, Kohji Kato, Naomi Tsuchida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Constitutive activation of mTORC1 signaling induced by biallelic loss-of-function mutations in SZT2 underlies a discernible neurodevelopmental disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0221482"}], "href": "https://doi.org/10.1371/journal.pone.0221482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31430354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31430354"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Cecilia Cattelani, Dominik Lesiak, Gudrun Liebscher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SZT2 Interactome Unravels New Functions of the KICSTOR Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells10102711"}], "href": "https://doi.org/10.3390/cells10102711"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34685691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34685691"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lina Basel-Vanagaite, Tova Hershkovitz, Eli Heyman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.07.005"}], "href": "https://doi.org/10.1016/j.ajhg.2013.07.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23932106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23932106"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "N Tsuchida, M Nakashima, A Miyauchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel biallelic SZT2 mutations in 3 cases of early-onset epileptic encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13061"}], "href": "https://doi.org/10.1111/cge.13061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28556953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28556953"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Michelle Falcone, Kemal O Yariz, David B Ross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An amino acid deletion inSZT2 in a family with non-syndromic intellectual disability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0082810"}], "href": "https://doi.org/10.1371/journal.pone.0082810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24324832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24324832"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ghada Kunter, Jill R Woloszynek, Daniel C Link "}, {"type": "b", "children": [{"type": "t", "text": "A truncation mutant of Csf3r cooperates with PML-RARα to induce acute myeloid leukemia in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Hematol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exphem.2011.08.013"}], "href": "https://doi.org/10.1016/j.exphem.2011.08.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21911095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21911095"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Amy Pizzino, Matthew Whitehead, Parisa Sabet Rasekh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SZT2 result in early-onset epileptic encephalopathy and leukoencephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38717"}], "href": "https://doi.org/10.1002/ajmg.a.38717"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29696782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29696782"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiaomin Sun, Xuefei Zhong, Tingsong Li "}, {"type": "b", "children": [{"type": "t", "text": "Novel SZT2 mutations in three patients with developmental and epileptic encephalopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.926"}], "href": "https://doi.org/10.1002/mgg3.926"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31397114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31397114"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Tasuku Tsukamoto, Takahiro Sogo, Tomoe Ueyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chimeric G-CSF Receptor-Mediated STAT3 Activation Contributes to Efficient Induction of Cardiomyocytes from Mouse Induced Pluripotent Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biotechnol J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/biot.201900052"}], "href": "https://doi.org/10.1002/biot.201900052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31469473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31469473"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Tarek El Halabi, Maya Dirani, Mostafa Hotait, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel possible familial cause of epilepsy of infancy with migrating focal seizures related to SZT2 gene variant."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia Open (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/epi4.12451"}], "href": "https://doi.org/10.1002/epi4.12451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33681650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33681650"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sai Yang, Li-Ming Yang, Hong-Mei Liao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinical phenotype and genetic characteristics of SZT2 related diseases: A case report and literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Seizure (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.seizure.2023.12.008"}], "href": "https://doi.org/10.1016/j.seizure.2023.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38134649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38134649"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Cecilia Cattelani, Ingrid Battistella, Francesca Di Leva, et al. 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Synonyms	EIEE18, C1ORF84, SZT2B, SZT2A, KIAA0467
Proteins	SZT2_HUMAN
NCBI Gene ID	23334
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SZT2 has 5,901 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for SZT2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SZT2 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 SZT2 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 SZT2 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 SZT2 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 SZT2 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 SZT2 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 SZT2 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 SZT2 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 SZT2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SZT2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SZT2 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 SZT2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SZT2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SZT2 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 SZT2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SZT2 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 SZT2 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 SZT2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SZT2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SZT2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SZT2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SZT2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SZT2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SZT2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SZT2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SZT2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SZT2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SZT2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SZT2 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 SZT2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving SZT2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SZT2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SZT2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SZT2 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 SZT2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SZT2 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 SZT2 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 SZT2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SZT2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SZT2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SZT2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.