THBS2

Chr 6AD

thrombospondin 2

Also known as: EDSCLL3, TSP2

NCBI Gene: 7058 ENSG00000186340 UniProt: P35442 OMIM: 188061

The protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and functions as an inhibitor of angiogenesis. Mutations cause Ehlers-Danlos syndrome, classic-like type 3, which primarily affects connective tissue and increases susceptibility to lumbar disc herniation. The gene is inherited in an autosomal dominant pattern and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ADLOEUF 0.352 OMIM phenotypes

Clinical Summary— THBS2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 148 VUS of 233 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.22 (0.14–0.35)

0≤0.351.4

Missense OE?0.77 (0.72–0.83)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 13 / 59.5Missense obs/exp: 587 / 758.7Syn Z: -0.25

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS148

Likely Benign26

Benign30

Conflicting1

Pathogenic

148

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	148	0	0	148
Likely Benign	0	18	2	6	26
Benign	0	8	3	19	30
Conflicting	—				1
Total	0	175	5	25	206

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

View in ClinVar →

75 pathogenic / likely-pathogenic (of 85) ClinVar copy-number / structural variants overlap THBS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →