SPOCK1

Chr 5

SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1

Also known as: SPOCK, TESTICAN, TIC1

NCBI Gene: 6695ENSG00000152377UniProt: Q08629

This gene encodes the protein core of a seminal plasma proteoglycan containing chondroitin- and heparan-sulfate chains. The protein's function is unknown, although similarity to thyropin-type cysteine protease-inhibitors suggests its function may be related to protease inhibition. [provided by RefSeq, Jul 2008]

80
ClinVar variants
13
Pathogenic / LP
0.83
pLI score
0
Active trials
Clinical Summary— SPOCK1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 59 VUS of 80 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.39LOEUF
pLI 0.826
Z-score 3.71
OE 0.17 (0.08–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.18Z-score
OE missense 0.79 (0.70–0.89)
190 obs / 241.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.08–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.70–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 4 / 23.4Missense obs/exp: 190 / 241.7Syn Z: -0.05

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS59
Likely Benign7
Benign1
13
Pathogenic
59
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
0
48
11
0
59
Likely Benign
0
2
2
3
7
Benign
0
1
0
0
1
Total05126380

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SPOCK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SPOCK1 promotes metastasis in pancreatic cancer via NF-κB-dependent epithelial-mesenchymal transition by interacting with IκB-α.
Cui X et al.·Cell Oncol (Dordr)
2022
[The role of the SPOCK1 protein in healthy and pathological liver processes].
Bárdos D et al.·Orv Hetil
2025Review
SPOCK: Master regulator of malignant tumors (Review).
Xiao M et al.·Mol Med Rep
2024Review
SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer.
Gan C et al.·BMC Gastroenterol
2023
SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion.
Liu Y et al.·J Transl Med
2023
Up-regulation of SPOCK1 induces epithelial-mesenchymal transition and promotes migration and invasion in esophageal squamous cell carcinoma.
Song X et al.·J Mol Histol
2015
SPOCK1/SIX1axis promotes breast cancer progression by activating AKT/mTOR signaling.
Xu M et al.·Aging (Albany NY)
2020
SPOCK1 contributes to the third-generation EGFR tyrosine kinase inhibitors resistance in lung cancer.
Gao Y et al.·J Cell Biochem
2019
SPOCK1 is regulated by CHD1L and blocks apoptosis and promotes HCC cell invasiveness and metastasis in mice.
Li Y et al.·Gastroenterology
2013
SPOCK1 promotes the invasion and metastasis of gastric cancer through Slug-induced epithelial-mesenchymal transition.
Chen D et al.·J Cell Mol Med
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
circ_PPAPDC1A is Associated with Brain Metastasis of Non-Small-Cell Lung Cancer via the miR-30a-3p/SPOCK1 Pathway.
Zou FW et al.·Ann Surg Oncol
2026
Senescence-associated miRNAs predict survival and modulate the tumor immune microenvironment via SPOCK1 targeting in clear cell renal cell carcinoma.
Song Z et al.·Urol Oncol
2025
SPOCK1 promotes the progression of breast cancer by modulating cancer-associated fibroblasts and exerts a synergistic effect with ANXA2.
Jie Y et al.·Front Oncol
2025🔓 Open Access
The oncogenic role of SPOCK1 in lung carcinoma by promoting immune evasion and its related mechanisms.
Lv G et al.·Cytotechnology
2025Functional
The Clinopathological and Prognostic Significance of SPOCK1 in Gynecological Cancers: A Bioinformatics Based Analysis.
Karaman E et al.·Biology (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools