THBS1

Chr 15

thrombospondin 1

Also known as: THBS, THBS-1, TSP, TSP-1, TSP1

NCBI Gene: 7057 ENSG00000137801 UniProt: P07996 OMIM: 188060

The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

376

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.23

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 1.000

Z-score 6.06

OE 0.13 (0.07–0.23)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.72Z-score

OE missense 0.72 (0.67–0.77)

516 obs / 721.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.23)

0≤0.351.4

Missense OE?0.72 (0.67–0.77)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 7 / 56.0Missense obs/exp: 516 / 721.4Syn Z: 1.70

Background carrier burden — how many people carry a rare variant somewhere in THBS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,275 rare PASS variants

Rare truncating (LoF)

1 in 5,300

71 rare PASS variants

Rare synonymous (reference)

1 in 55

522 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THBS1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 66	1 in 5,600
South Asian	~43k	1 in 41	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 37	1 in 3,300
European (Finnish)	~27k	1 in 170	1 in 3,800
Admixed American	~22k	1 in 55	1 in 2,800
African / African American	~21k	1 in 57	≈ 1 in 8,400
East Asian	~20k	1 in 57	1 in 1,100
Ashkenazi Jewish	~13k	1 in 290	none seen
Middle Eastern	~2,884	1 in 44	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 20 of 21 coding exons well covered in gnomAD exomes; exon 22 marginal. Genomes: all 21.? see exons ↓