NIT1 Gene

Name	nitrilase 1
Description	This gene encodes a member of the nitrilase protein family with homology to bacterial and plant nitrilases, enzymes that cleave nitriles and organic amides to the corresponding carboxylic acids plus ammonia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMammalian NIT1 has emerged as a multifunctional protein with a prominent role in regulating cell growth and tumor suppression. In mouse cells, NIT1 is widely expressed, sharing partial tissue distribution with its partner Fhit, and its loss leads to accelerated cell proliferation, resistance to DNA‐damage stress, and increased cyclin D1 expression. In parallel, studies in colorectal carcinoma demonstrate that reduced NIT1 expression associates with poor differentiation and enhanced invasive properties; functional evidence indicates that NIT1 induces cell cycle arrest and apoptosis through recruitment of Smad2/3 to the TGFβ receptor and activation of the TGFβ–Smad2/3 signaling cascade, a process further augmented by a positive feedback loop involving SMAD3 binding to the NIT1 promoter."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, biochemical analyses have revealed that NIT1 physically associates with Fhit, forming a tetrameric structure reminiscent of the NitFhit fusion proteins observed in invertebrates. This interaction, along with shared binding partners such as Hsp60 and Ubc9, supports the notion that NIT1 operates within common tumor suppressor pathways. However, divergent roles are apparent in lung cancer models; in transgenic mice carrying oncogenic Kras, deletion of NIT1 resulted in markedly reduced tumor volumes and heightened cisplatin sensitivity, while high NIT1 expression in human lung cancer cells facilitates cell survival and chemoresistance, suggesting that NIT1’s function may be context‐dependent."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther insights reveal that although NIT1 belongs to the nitrilase superfamily—with homologs in plants and bacteria known to catalyze the hydrolysis of nitrile compounds—its enzymatic activity does not appear to contribute significantly to the metabolism of certain xenobiotics, as illustrated by its lack of involvement in vildagliptin hydrolysis despite high hepatic expression. In addition, recent genetic findings have implicated loss‐of‐function variants in NIT1 as the cause of a recessively inherited cerebral small vessel disease, thereby extending the relevance of NIT1 to neurological vascular pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shuho Semba, Shuang-Yin Han, Haiyan R Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biological functions of mammalian Nit1, the counterpart of the invertebrate NitFhit Rosetta stone protein, a possible tumor suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M603590200"}], "href": "https://doi.org/10.1074/jbc.M603590200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16864578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16864578"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chun Lin, Jianming Zhang, Yanxia Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIT1 suppresses tumour proliferation by activating the TGFβ1-Smad2/3 signalling pathway in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0333-3"}], "href": "https://doi.org/10.1038/s41419-018-0333-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29449642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29449642"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sonnhild Mittag, Franziska Wetzel, Sebastian Y Müller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells12030353"}], "href": "https://doi.org/10.3390/cells12030353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36766695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36766695"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong Antican Wang, Yunguang Sun, Justin M Le Blanc, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitrilase 1 modulates lung tumor progression in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.7820"}], "href": "https://doi.org/10.18632/oncotarget.7820"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26967383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26967383"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mitsutoshi Asakura, Masataka Nakano, Kohei Hayashida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human nitrilase-like protein does not catalyze the hydrolysis of vildagliptin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Pharmacokinet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2133/dmpk.DMPK-14-RG-027"}], "href": "https://doi.org/10.2133/dmpk.DMPK-14-RG-027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25008847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25008847"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julie W Rutten, Minne N Cerfontaine, Kyra L Dijkstra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic NIT1 variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gim.2024.101105"}], "href": "https://doi.org/10.1016/j.gim.2024.101105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38430071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38430071"}]}]}]}
Proteins	NIT1_HUMAN
NCBI Gene ID	4817
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NIT1 has 6,801 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for NIT1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NIT1 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by NIT1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NIT1 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 NIT1 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 NIT1 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 NIT1 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 NIT1 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 NIT1 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 NIT1 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 NIT1 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 NIT1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NIT1 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 NIT1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NIT1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NIT1 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 NIT1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NIT1 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 NIT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing NIT1 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 NIT1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NIT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing NIT1 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	cellular components co-occuring with NIT1 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 NIT1 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 NIT1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NIT1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NIT1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NIT1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NIT1 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 NIT1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NIT1 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 NIT1 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 NIT1 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 NIT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NIT1 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 NIT1 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 NIT1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NIT1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing NIT1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NIT1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NIT1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.