THBS2

Chr 6AD

thrombospondin 2

Also known as: EDSCLL3, TSP2

NCBI Gene: 7058ENSG00000186340UniProt: P35442

The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Ehlers-Danlos syndrome, classic-like, 3MIM #620865
AD
{Lumbar disc herniation, susceptibility to}MIM #603932
UniProtIntervertebral disc disease
285
ClinVar variants
73
Pathogenic / LP
0.56
pLI score
0
Active trials
Clinical Summary— THBS2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 153 VUS of 285 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.35LOEUF
pLI 0.556
Z-score 5.58
OE 0.22 (0.14–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.21Z-score
OE missense 0.77 (0.72–0.83)
587 obs / 758.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.22 (0.14–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.72–0.83)
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.1.02
0≤1.21.6
LoF obs/exp: 13 / 59.5Missense obs/exp: 587 / 758.7Syn Z: -0.25

ClinVar Variant Classifications

285 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic4
VUS153
Likely Benign28
Benign30
Conflicting1
69
Pathogenic
4
Likely Pathogenic
153
VUS
28
Likely Benign
30
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
68
0
69
Likely Pathogenic
0
0
4
0
4
VUS
0
147
6
0
153
Likely Benign
0
16
6
6
28
Benign
0
8
3
19
30
Conflicting
—1
Total01728725285

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

View in ClinVar →

Protein Context — Lollipop Plot

THBS2 · 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
THROMBOSPONDIN II; THBS2
MIM #188061 · *

?Ehlers-Danlos syndrome, classic-like, 3

MIM #620865

Molecular basis of disorder known

Autosomal dominant

{Lumbar disc herniation, susceptibility to}

MIM #603932

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CAF-macrophage crosstalk in tumour microenvironments governs the response to immune checkpoint blockade in gastric cancer peritoneal metastases.
Li Y et al.·Gut
2025Clinical trial
Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.
Hoshino A et al.·Cell
2020
Integrating single-cell and bulk RNA sequencing data unveils antigen presentation and process-related CAFS and establishes a predictive signature in prostate cancer.
Wang W et al.·J Transl Med
2024
Heterozygous THBS2 pathogenic variant causes Ehlers-Danlos syndrome with prominent vascular features in humans and mice.
Hadar N et al.·Eur J Hum Genet
2024
Multi-scale integrative analyses identify THBS2(+) cancer-associated fibroblasts as a key orchestrator promoting aggressiveness in early-stage lung adenocarcinoma.
Yang H et al.·Theranostics
2022
Cancer-associated fibroblasts drive lung adenocarcinoma progression via THBS2-mediated epithelial-mesenchymal transition.
Ren Y et al.·Oncogene
2025
THBS1 and THBS2 Enhance the In Vitro Proliferation, Adhesion, Migration and Invasion of Intrahepatic Cholangiocarcinoma Cells.
Corbella E et al.·Int J Mol Sci
2024
Exosomal ALPPL2 and THBS2 as biomarkers for early detection and disease monitoring of pancreatic ductal adenocarcinoma.
Halder K et al.·Br J Cancer
2025
Enhanced THBS2 promotes collagen synthesis and inflammatory secretome of fibroblasts in idiopathic pulmonary fibrosis.
Yu L et al.·Sci Rep
2025
Transcriptomic Signatures in Colorectal Cancer Progression.
Ershov P et al.·Curr Mol Med
2023Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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