THSD1

Chr 13

thrombospondin type 1 domain containing 1

Also known as: ANIB12, LMPHM13, TMTSP, UNQ3010

NCBI Gene: 55901 ENSG00000136114 UniProt: Q9NS62

The protein is a positive regulator of focal adhesion assembly that modulates endothelial cell attachment to the extracellular matrix through its thrombospondin domain. Mutations cause intracranial berry aneurysms and lymphatic malformations, reflecting its role in vascular development and integrity. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific condition.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in a number of proteins involved in the complement pathway, as well as in extracellular matrix proteins. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jan 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLymphatic malformation 13

UniProtAneurysm, intracranial berry, 12

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.88

LOEUF

Multiple*

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?

0.88LOEUF

pLI 0.000

Z-score 2.04

OE 0.58 (0.39–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.50Z-score

OE missense 0.94 (0.87–1.01)

452 obs / 482.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.39–0.88)

0≤0.351.4

Missense OE?0.94 (0.87–1.01)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 16 / 27.5Missense obs/exp: 452 / 482.7Syn Z: 0.03

Background carrier burden — how many people carry a rare variant somewhere in THSD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

1,092 rare PASS variants

Rare truncating (LoF)

1 in 1,400

113 rare PASS variants

Rare synonymous (reference)

1 in 83

436 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THSD1. 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 80	1 in 1,500
South Asian	~43k	1 in 79	1 in 1,000
Remaining (unassigned)	~30k	1 in 65	1 in 1,200
European (Finnish)	~27k	1 in 220	1 in 1,300
Admixed American	~22k	1 in 70	1 in 1,800
African / African American	~21k	1 in 73	1 in 980
East Asian	~20k	1 in 63	1 in 1,500
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 58	≈ 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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓