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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SPOCK1
SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1
Chromosome 5 · 5q31.2
NCBI Gene: 6695Ensembl: ENSG00000152377.15HGNC: HGNC:11251UniProt: Q08629
75PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular matrixmetalloendopeptidase inhibitor activitycysteine-type endopeptidase inhibitor activityextracellular matrix structural constituentatrial fibrillationperiapical tissue diseasesmoking initiationJaundice
✦AI Summary

SPOCK1 is a matricellular proteoglycan with dual roles in normal physiology and cancer pathology. Structurally, SPOCK1 is an extracellular matrix protein with calcium-binding domains and protease inhibitory activity, though it can also localize intracellularly near mitochondria and in the nucleus 1. In normal tissues, SPOCK1 is expressed at low levels and may contribute to cell-cell and cell-matrix interactions, particularly in neural tissues including synapses and neuromuscular junctions 2. Pathologically, SPOCK1 functions as a critical oncogenic mediator across multiple cancer types. In prostate cancer, SPOCK1 overexpression promotes cell viability, colony formation, and metastasis by modulating cell cycle progression and apoptosis 3. Similarly, in pancreatic cancer, SPOCK1 activates NF-κB signaling via IκBα interaction to drive epithelial-mesenchymal transition (EMT) and metastasis 4. In hepatocellular carcinoma, SPOCK1 inhibits apoptosis and promotes proliferation through MAPK and Src family kinase pathways 1. SPOCK1 also mediates therapeutic resistance: in lung adenocarcinoma, RBM15-dependent m6A modification of SPOCK1 mRNA promotes osimertinib resistance through EMT activation 5, while in colorectal cancer, SPOCK1 drives 5-FU resistance via PRRX1 regulation 6. Clinically, SPOCK1 represents a promising biomarker and therapeutic target, with expression correlating with poor prognosis, metastasis, and drug resistance across malignancies 7.

Sources cited
1
SPOCK1 overexpression promotes prostate cancer cell viability, colony formation, tumor growth, and metastasis; knockdown causes cell cycle arrest and increased apoptosis
PMID: 27486308
2
RBM15-mediated m6A modification of SPOCK1 mRNA promotes osimertinib resistance in lung adenocarcinoma through EMT activation
PMID: 39528815
3
SPOCK1 is a matricellular proteoglycan with oncogenic potential across 36 tumor types; localizes in mitochondria and neural synapses; physiological function remains partially elucidated
PMID: 35235422
4
SPOCK1 promotes pancreatic cancer metastasis via NF-κB-dependent EMT through direct interaction with IκBα
PMID: 34855159
5
SPOCK1 expression is low in healthy liver but increases significantly in HCV infection, cirrhosis, and liver cancer; promotes cell growth and migration while inhibiting apoptosis
PMID: 39827432
6
SPOCK1 upregulation confers 5-FU resistance in colorectal cancer through PRRX1-regulated apoptosis signaling
PMID: 35462225
7
SPOCK1 increases in hepatocyte cytoplasm during hepatocarcinogenesis; colocalizes with mitochondrial markers; inhibits proliferation and upregulates p21/p27 via MAPK and Src family kinase pathways
PMID: 35186754
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.47Moderate
periapical tissue diseaseOpen Targets
0.36Weak
smoking initiationOpen Targets
0.36Weak
JaundiceOpen Targets
0.32Weak
psoriasisOpen Targets
0.32Weak
psoriasis vulgarisOpen Targets
0.31Weak
mathematical abilityOpen Targets
0.31Weak
injuryOpen Targets
0.29Weak
generalised epilepsyOpen Targets
0.29Weak
abnormality of serum enzyme levelsOpen Targets
0.28Weak
biliary tract diseaseOpen Targets
0.28Weak
allergic diseaseOpen Targets
0.26Weak
carotid artery diseaseOpen Targets
0.26Weak
type 2 diabetes mellitusOpen Targets
0.26Weak
hidradenitisOpen Targets
0.23Weak
food allergyOpen Targets
0.23Weak
liver diseaseOpen Targets
0.23Weak
frozen shoulderOpen Targets
0.17Weak
response to xenobiotic stimulusOpen Targets
0.15Weak
cervical carcinomaOpen Targets
0.14Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SPARCProtein interaction89%MMP16Protein interaction81%TGProtein interaction72%FSTProtein interaction71%NAV1Shared pathway30%NAV2Shared pathway20%
Tissue Expression6 tissues
Brain
100%
Heart
20%
Ovary
1%
Lung
1%
Bone Marrow
0%
Liver
0%
Gene Interaction Network
Click a node to explore
SPOCK1SPARCMMP16TGFSTNAV1NAV2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q08629
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.38Tolerant
Observed/Expected LoF0.40 [0.28–0.59]
RankingsWhere SPOCK1 stands among ~20K protein-coding genes
  • #6,367of 20,598
    Most Researched75
  • #3,947of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedSPOCK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SPOCK1 promotes tumor growth and metastasis in human prostate cancer.
PMID: 27486308
Drug Des Devel Ther · 2016
1.00
2
RBM15 facilitates osimertinib resistance of lung adenocarcinoma through m6A-dependent epigenetic silencing of SPOCK1.
PMID: 39528815
Oncogene · 2025
0.90
3
SPOCK1 with unexpected function. The start of a new career.
PMID: 35235422
Am J Physiol Cell Physiol · 2022
0.80
4
Epigenetic regulation of triple negative breast cancer (TNBC) by TGF-β signaling.
PMID: 34326372
Sci Rep · 2021
0.70
5
SPOCK1 promotes metastasis in pancreatic cancer via NF-κB-dependent epithelial-mesenchymal transition by interacting with IκB-α.
PMID: 34855159
Cell Oncol (Dordr) · 2022
0.60