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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SPOCK3
SPARC (osteonectin), cwcv and kazal like domains proteoglycan 3
Chromosome 4 · 4q32.3
NCBI Gene: 50859Ensembl: ENSG00000196104.11HGNC: HGNC:13565UniProt: A0A0A0MTJ2
24PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular matrixmetalloendopeptidase inhibitor activityregulation of cell-substrate adhesionGO:0005615Hypercholesterolemiatrauma complicationcomplicationresponse to antihypertensive drug
✦AI Summary

SPOCK3 (SPARC, cwcv and kazal like domains proteoglycan 3) is an extracellular matrix proteoglycan that functions as a regulatory component in multiple biological processes. The protein serves as a metalloendopeptidase inhibitor, specifically inhibiting the processing of pro-matrix metalloproteinase 2 (MMP-2) by MT1-MMP and MT3-MMP, which may interfere with tumor invasion 1. SPOCK3 demonstrates significant involvement in neurological processes, with genetic variants associated with adult ADHD and personality disorders 23. The protein shows region-specific accumulation in Alzheimer's disease brain tissue, particularly in the hippocampus, where it colocalizes with amyloid plaques and exhibits pronounced regional specificity compared to other brain areas 4. In cancer biology, SPOCK3 functions as a protective prognostic factor in prostate cancer, where high expression correlates with better disease-free survival and enhanced immune cell infiltration including mast cells, NK cells, and B cells 5. The protein also serves as a prognostic biomarker in colorectal cancer, with elevated expression in tumor tissues compared to normal tissues 6. Additionally, SPOCK3 expression changes in response to environmental toxin exposure, suggesting its potential role as a biomarker for chemical-induced cellular stress 7.

Sources cited
1
SPOCK3 inhibits MMP-2 processing and may interfere with tumor invasion
PMID: 39392048
2
SPOCK3 genetic variants are associated with adult ADHD and personality disorders
PMID: 24292267
3
SPOCK3 is part of neurodevelopmental network genes associated with adult ADHD
PMID: 28097908
4
SPOCK3 shows region-specific accumulation in Alzheimer's disease brain tissue, particularly in hippocampus
PMID: 40705253
5
SPOCK3 functions as protective prognostic factor in prostate cancer with enhanced immune cell infiltration
PMID: 37563543
6
SPOCK3 serves as prognostic biomarker in colorectal cancer with elevated tumor expression
PMID: 41257959
7
SPOCK3 expression changes in response to environmental toxin exposure
PMID: 40945090
Disease Associationsⓘ20
HypercholesterolemiaOpen Targets
0.32Weak
complicationOpen Targets
0.32Weak
trauma complicationOpen Targets
0.32Weak
response to antihypertensive drugOpen Targets
0.31Weak
medical procedureOpen Targets
0.31Weak
liver diseaseOpen Targets
0.31Weak
cervical carcinomaOpen Targets
0.30Weak
adolescent idiopathic scoliosisOpen Targets
0.25Weak
congenital anomaly of cardiovascular systemOpen Targets
0.24Weak
duodenitisOpen Targets
0.24Weak
alopecia areataOpen Targets
0.23Weak
response to vaccineOpen Targets
0.20Weak
osteitis deformansOpen Targets
0.20Weak
pericarditisOpen Targets
0.17Weak
hyperpituitarismOpen Targets
0.17Weak
tooth diseaseOpen Targets
0.17Weak
carotid artery diseaseOpen Targets
0.16Weak
lymphoid leukemiaOpen Targets
0.16Weak
esophageal diseaseOpen Targets
0.16Weak
kidney diseaseOpen Targets
0.15Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MMP14Protein interaction85%MMP16Protein interaction85%SPINT2Shared pathway20%CCDC125Shared pathway20%FRMD5Shared pathway20%AP1ARShared pathway20%
Tissue Expression6 tissues
Brain
100%
Ovary
3%
Bone Marrow
2%
Heart
1%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
SPOCK3MMP14MMP16SPINT2CCDC125FRMD5AP1AR
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BQ16
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.65LoF Tolerant
pLIⓘ
0.15Tolerant
Observed/Expected LoF0.43 [0.29–0.65]
RankingsWhere SPOCK3 stands among ~20K protein-coding genes
  • #13,317of 20,598
    Most Researched24
  • #4,735of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedSPOCK3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SPOCK3, a risk gene for adult ADHD and personality disorders.
PMID: 24292267
Eur Arch Psychiatry Clin Neurosci · 2014
1.00
2
SPOCK: Master regulator of malignant tumors (Review).
PMID: 39392048
Mol Med Rep · 2024
0.90
3
Brain Region-Specific Accumulation of Amyloidosis-Associated Proteins in Postmortem Brain Tissues of Alzheimer's Disease Patients.
PMID: 40705253
Mol Neurobiol · 2025
0.80
4
Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder.
PMID: 28097908
World J Biol Psychiatry · 2018
0.70
5
Mechanism of prognostic marker SPOCK3 affecting malignant progression of prostate cancer and construction of prognostic model.
PMID: 37563543
BMC Cancer · 2023
0.60