THBS3

Chr 1

thrombospondin 3

Also known as: TSP3

NCBI Gene: 7059 ENSG00000169231 UniProt: P49746

The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.93

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 2.00

OE 0.71 (0.56–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.78Z-score

OE missense 0.79 (0.73–0.85)

455 obs / 574.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.56–0.93)

0≤0.351.4

Missense OE?0.79 (0.73–0.85)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 41 / 57.4Missense obs/exp: 455 / 574.9Syn Z: 1.60

Background carrier burden — how many people carry a rare variant somewhere in THBS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 64

1,122 rare PASS variants

Rare truncating (LoF)

1 in 580

201 rare PASS variants

Rare synonymous (reference)

1 in 75

461 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THBS3. 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 69	1 in 560
South Asian	~43k	1 in 65	1 in 370
Remaining (unassigned)	~30k	1 in 55	1 in 740
European (Finnish)	~27k	1 in 160	1 in 1,600
Admixed American	~22k	1 in 50	1 in 1,100
African / African American	~21k	1 in 85	1 in 660
East Asian	~20k	1 in 60	1 in 690
Ashkenazi Jewish	~13k	1 in 180	1 in 650
Middle Eastern	~2,884	1 in 81	≈ 1 in 960

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): All 23 coding exons well covered in gnomAD exomes and genomes.? see exons ↓