RECK Gene

Name	reversion-inducing-cysteine-rich protein with kazal motifs
Description	The protein encoded by this gene is a cysteine-rich, extracellular protein with protease inhibitor-like domains whose expression is suppressed strongly in many tumors and cells transformed by various kinds of oncogenes. In normal cells, this membrane-anchored glycoprotein may serve as a negative regulator for matrix metalloproteinase-9, a key enzyme involved in tumor invasion and metastasis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRECK is a membrane‐anchored glycoprotein that functions as a critical tumor suppressor by inhibiting extracellular proteolysis. By directly impeding the activation and secretion of several matrix metalloproteinases—including MMP‑2, MMP‑9, and membrane‐type MMPs—it helps maintain extracellular matrix integrity and thereby limits tumor cell invasion, metastasis, and angiogenesis. Forced expression of RECK in various tumor‐derived cell lines has been shown to reduce proteolytic activity and suppress metastatic behavior, underscoring its role as a transformation suppressor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRECK expression is highly dynamic and is controlled by multiple, interrelated mechanisms. Epigenetic modifiers such as histone deacetylase inhibitors can restore RECK levels, while oncogenic signals—including those from HER‑2/neu and RAS—suppress its transcription via promoter methylation and altered transcription factor binding. In addition, a broad spectrum of microRNAs (for example, miR‑21, miR‑182, miR‑96, miR‑25, miR‑15a/–15b, miR‑222, miR‑135b, miR‑221, and miR‑200b/c) directly target the RECK transcript and promote its downregulation in a range of cancers (including glioma, osteosarcoma, prostate, bladder, gastric, esophageal, colorectal, lung, hepatocellular carcinoma, and neuroblastoma). Genetic polymorphisms and signaling inputs—from STAT3 activation to the effects of growth factors like G‑CSF—further modulate RECK levels, collectively contributing to enhanced invasion and metastasis in tumors with low RECK expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical function in regulating extracellular matrix remodeling, emerging evidence suggests that RECK also modulates the tumor microenvironment and cancer stem-like properties. By interacting with metalloproteinases and members of the ADAM protease family, RECK can influence signaling pathways such as Notch, which in turn may affect cell differentiation and stemness. These novel insights into RECK’s broader regulatory roles not only enhance our understanding of tumor biology but also underscore its potential as a prognostic biomarker and a target for anti‐metastatic as well as anti‐stemness therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "32", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Toshihiko Masui, Ryuichiro Doi, Takatomo Koshiba, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The silencing of RECK gene is associated with promoter hypermethylation and poor survival in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.4038"}], "href": "https://doi.org/10.7150/ijbs.4038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22419890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22419890"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Chen Xin, Bao Buhe, Lu Hongting, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-15a promotes neuroblastoma migration by targeting reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and regulating matrix metalloproteinase-9 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.12074"}], "href": "https://doi.org/10.1111/febs.12074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23176145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23176145"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Liang Yang, Jianshuai Jiang "}, {"type": "b", "children": [{"type": "t", "text": "GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2019/2973289"}], "href": "https://doi.org/10.1155/2019/2973289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30733959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30733959"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "H-Y Lin, C-H Chiang, W-C Hung "}, {"type": "b", "children": [{"type": "t", "text": "STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2013.349"}], "href": "https://doi.org/10.1038/bjc.2013.349"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23820254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23820254"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Jingwei Li, Kailei Jiang, Fujie Zhao "}, {"type": "b", "children": [{"type": "t", "text": "Icariin regulates the proliferation and apoptosis of human ovarian cancer cells through microRNA-21 by targeting PTEN, RECK and Bcl-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2015.3891"}], "href": "https://doi.org/10.3892/or.2015.3891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25845681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25845681"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Yan Li, Dan Xu, Chunyang Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2965"}], "href": "https://doi.org/10.18632/oncotarget.2965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25537516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25537516"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Kun-Jing Hong, Deng-Chyang Wu, Kuang-Hung Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RECK inhibits stemness gene expression and tumorigenicity of gastric cancer cells by suppressing ADAM-mediated Notch1 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.24434"}], "href": "https://doi.org/10.1002/jcp.24434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23881612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23881612"}]}]}]}
Synonyms	ST15
Proteins	RECK_HUMAN
NCBI Gene ID	8434
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RECK has 6,486 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

RECK 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 RECK gene relative to other tissues from the Allen Brain Atlas Adult Human 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 RECK 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 RECK 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 RECK 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 RECK gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving RECK protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of RECK 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 RECK 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 RECK 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 RECK gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RECK 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 RECK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RECK protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RECK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RECK 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 RECK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RECK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RECK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RECK 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 RECK 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 RECK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RECK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RECK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RECK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RECK 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 RECK gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RECK gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RECK 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 RECK 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 RECK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RECK 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 RECK 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 RECK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RECK 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 RECK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RECK gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with RECK 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 RECK gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RECK gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing RECK from the GeneSigDB Published Gene Signatures dataset.