SPOCK2 Gene

Name	sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2
Description	This gene encodes a protein which binds with glycosaminoglycans to form part of the extracellular matrix. The protein contains thyroglobulin type-1, follistatin-like, and calcium-binding domains, and has glycosaminoglycan attachment sites in the acidic C-terminal region. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPOCK2, a member of the SPOCK (SPARC/osteonectin, cwcv and kazal‐like) family of extracellular proteoglycans, has emerged as a critical modulator in multiple human cancers. In breast carcinomas, genomic alterations affecting SPOCK2 are associated with extracellular matrix remodeling and clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In endometrial cancer, decreased SPOCK2 levels correlate with myometrial invasion and distant metastasis, while forced expression modulates the membrane type‐1 matrix metalloproteinase (MT1‐MMP)/MMP2 pathway to inhibit proliferation, invasion, adhesion, and even apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, epigenetic repression of SPOCK2 by EZH2 in lung adenocarcinoma accelerates tumor cell proliferation, migration, and invasion—effects that are reversible with EZH2 inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, early loss of SPOCK2 expression has been implicated as an initiating event during the malignant transformation of endometriosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and its presence in the extracellular matrix of pancreatic ductal adenocarcinoma underscores a putative role in tumorigenicity and drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In melanoma, reduced SPOCK2 enhances MAPK/ERK signaling, thereby promoting cell cycle progression, migration, invasion, and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " A recent comprehensive review further emphasizes that the SPOCK gene family, including SPOCK2, regulates matrix metalloproteinases, impacts epithelial–mesenchymal transition, and influences cell cycle dynamics, highlighting its potential as a target in anticancer strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSPOCK2 also plays an important role in extracellular matrix proteolysis. Studies on testican family proteins have shown that testican-2—the protein encoded by SPOCK2—interacts with and can inactivate inhibitory events mediated by other family members on MT-MMP–driven pro-MMP-2 activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In vascular tissues, particularly in the context of sporadic non-syndromic thoracic aortic aneurysms, upregulation of SPOCK2 disrupts the normal inhibitory network of matrix metalloproteinases, thereby enhancing proteolysis of extracellular matrix components and contributing to pathological remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer and matrix remodeling, SPOCK2 is emerging as a biomarker of kidney health. Single-cell RNA sequencing and immunohistochemical analyses have demonstrated that SPOCK2 is expressed exclusively in podocytes. In this setting, testican-2 is secreted into circulation, where its levels correlate positively with glomerular filtration rate. Functional in vitro studies further indicate that SPOCK2 supports glomerular endothelial tube formation and motility, implying a supportive role in maintaining glomerular integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, SPOCK2 may influence immune responses. Biochemical characterization of recombinant testican-2 revealed that its thyroglobulin type-1 domain binds to the complement subcomponent C1q, suggesting that SPOCK2 might participate in regulating classical complement pathway activation and modulating inflammatory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Silje H Nordgard, Fredrik E Johansen, Grethe I G Alnaes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20569"}], "href": "https://doi.org/10.1002/gcc.20569"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18398821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18398821"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fang Ren, Danni Wang, Yizi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPOCK2 Affects the Biological Behavior of Endometrial Cancer Cells by Regulation of MT1-MMP and MMP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s43032-020-00197-4"}], "href": "https://doi.org/10.1007/s43032-020-00197-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32430715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32430715"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yang Liu, Xiaoxi Fan, Changrui Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPOCK2 and SPRED1 function downstream of EZH2 to impede the malignant progression of lung adenocarcinoma in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-023-00855-0"}], "href": "https://doi.org/10.1007/s13577-023-00855-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36629984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36629984"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fang Ren, Yizi Wang, Peng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of SPOCK2 promotes the proliferation, adhesion, and invasion of endometrial epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gynecol Endocrinol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/09513590.2020.1812567"}], "href": "https://doi.org/10.1080/09513590.2020.1812567"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32851893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32851893"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ughur Aghamaliyev, Kaifeng Su, Maximilian Weniger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPOCK2 gene expression is downregulated in pancreatic ductal adenocarcinoma cells and correlates with prognosis of patients with pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-023-04845-5"}], "href": "https://doi.org/10.1007/s00432-023-04845-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37188984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37188984"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ji Young Kang, Hyeijin Cho, Minchan Gil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel prognostic marker SPOCK2 regulates tumour progression in melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.15092"}], "href": "https://doi.org/10.1111/exd.15092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38888196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38888196"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mingyuan Xiao, Jiancheng Xue, Enli Jin "}, {"type": "b", "children": [{"type": "t", "text": "SPOCK: Master regulator of malignant tumors (Review)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2024.13355"}], "href": "https://doi.org/10.3892/mmr.2024.13355"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39392048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39392048"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mitsutoshi Nakada, Hisashi Miyamori, Junkoh Yamashita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by other testican family proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12810672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12810672"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anna Chiarini, Francesco Onorati, Maddalena Marconi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Studies on sporadic non-syndromic thoracic aortic aneurysms: II. Alterations of extra-cellular matrix components and focal adhesion proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Prev Cardiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/2047487318759120"}], "href": "https://doi.org/10.1177/2047487318759120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29708036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29708036"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Debby Ngo, Donghai Wen, Yan Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating testican-2 is a podocyte-derived marker of kidney health."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2009606117"}], "href": "https://doi.org/10.1073/pnas.2009606117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32958645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32958645"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Donghai Wen, Linda Zhou, Zihe Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testican-2 Is Associated with Reduced Risk of Incident ESKD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2022020216"}], "href": "https://doi.org/10.1681/ASN.2022020216"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36288905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36288905"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Miha Pavsic, Turk Vito, Brigita Lenarcic "}, {"type": "b", "children": [{"type": "t", "text": "Purification and characterization of a recombinant human testican-2 expressed in baculovirus-infected Sf9 insect cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Expr Purif (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pep.2007.09.010"}], "href": "https://doi.org/10.1016/j.pep.2007.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17950619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17950619"}]}]}]}
Synonyms	TESTICAN-2
Proteins	TICN2_HUMAN
NCBI Gene ID	9806
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SPOCK2 has 6,741 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 114 datasets.

Click the + buttons to view associations for SPOCK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPOCK2 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 SPOCK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SPOCK2 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 SPOCK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SPOCK2 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 SPOCK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SPOCK2 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 SPOCK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SPOCK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SPOCK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SPOCK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SPOCK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SPOCK2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SPOCK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SPOCK2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SPOCK2 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 SPOCK2 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 SPOCK2 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 SPOCK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SPOCK2 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 SPOCK2 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 SPOCK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SPOCK2 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 SPOCK2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SPOCK2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SPOCK2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.