LTBP3

Chr 11

latent transforming growth factor beta binding protein 3

Also known as: DASS, GPHYSD3, LTBP-3, LTBP2, STHAG6, pp6425

NCBI Gene: 4054 ENSG00000168056 UniProt: Q14767

The protein forms complexes with transforming growth factor beta (TGF-beta) and plays an integral structural role in elastic fiber organization and assembly in the extracellular matrix. Mutations cause geleophysic dysplasia 3 and dental anomalies with short stature, affecting skeletal development and dental formation. The gene shows both autosomal recessive and autosomal dominant inheritance patterns and is highly constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGlaucoma 3, primary congenital, D

UniProtMicrospherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma

UniProtWeill-Marchesani syndrome 3

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — LTBP3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in LTBP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,708 rare PASS variants

Rare truncating (LoF)

1 in 820

253 rare PASS variants

Rare synonymous (reference)

1 in 67

872 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LTBP3. 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 51	1 in 870
South Asian	~43k	1 in 39	1 in 720
Remaining (unassigned)	~30k	1 in 37	1 in 1,200
European (Finnish)	~27k	1 in 120	1 in 610
Admixed American	~22k	1 in 45	1 in 860
African / African American	~21k	1 in 41	1 in 1,500
East Asian	~20k	1 in 46	1 in 380
Ashkenazi Jewish	~13k	1 in 170	1 in 1,100
Middle Eastern	~2,884	1 in 39	≈ 1 in 1,400

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): 26 of 28 coding exons well covered in gnomAD exomes; exons 1, 28 marginal. Genomes: all 28.? see exons ↓