LTBP3

Chr 11ARAD

latent transforming growth factor beta binding protein 3

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

NCBI Gene: 4054ENSG00000168056UniProt: Q14767

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]

Primary Disease Associations & Inheritance

Dental anomalies and short statureMIM #601216
AR
Geleophysic dysplasia 3MIM #617809
AD
UniProtGlaucoma 3, primary congenital, D
UniProtMicrospherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma
UniProtWeill-Marchesani syndrome 3
396
ClinVar variants
22
Pathogenic / LP
0.69
pLI score
0
Active trials
Clinical Summary— LTBP3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 256 VUS of 396 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.686
Z-score 5.89
OE 0.21 (0.14–0.34)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.85Z-score
OE missense 0.71 (0.66–0.76)
553 obs / 776.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.14–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.66–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 14 / 65.4Missense obs/exp: 553 / 776.4Syn Z: 0.89

ClinVar Variant Classifications

396 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic11
VUS256
Likely Benign114
Benign1
Conflicting3
11
Pathogenic
11
Likely Pathogenic
256
VUS
114
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
4
0
11
Likely Pathogenic
10
0
1
0
11
VUS
2
229
22
3
256
Likely Benign
0
1
50
63
114
Benign
0
0
1
0
1
Conflicting
—3
Total192307866396

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

View in ClinVar →

Protein Context — Lollipop Plot

LTBP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LTBP3-related platyspondyly with amelogenesis imperfecta

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dental anomalies and short stature

MIM #601216

Molecular basis of disorder known

Autosomal recessive

Geleophysic dysplasia 3

MIM #617809

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — LTBP3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding genotypic and phenotypic spectrums of LTBP3 variants in dental anomalies and short stature syndrome.
Kantaputra P et al.·Clin Genet
2022
Aortic root dilatation and mitral valve prolapse in three siblings with dental anomalies and short stature syndrome due to a homozygous novel LTBP3 variant.
Biçer BB et al.·Cardiol Young
2025Case report
LTBP3 Pathogenic Variants Predispose Individuals to Thoracic Aortic Aneurysms and Dissections.
Guo DC et al.·Am J Hum Genet
2018
[IDENTIFICATION OF A NOVEL LTBP3 GENE PATHOGENIC VARIANT IN DRUZE ARAB PATIENTS PRESENTED WITH SYNDROMIC SHORT STATURE WITH BRACHYOLMIA AND AMELOGENESIS IMPERFECTA].
Hadid Y et al.·Harefuah
2023Cohort
Genotype-phenotype correlation and expansion of orodental anomalies in LTBP3-related disorders.
Intarak N et al.·Mol Genet Genomics
2019Case report
Tooth agenesis: What do we know and is there a connection to cancer?
Bonczek O et al.·Clin Genet
2021Review
Protein profiling in plasma for biomarkers of seizure.
Akel S et al.·Epilepsy Res
2023
Novel LTBP3 mutations associated with thoracic aortic aneurysms and dissections.
Zhu G et al.·Orphanet J Rare Dis
2021
Dysregulation of cell migration by matrix metalloproteinases in geleophysic dysplasia.
Morales AA et al.·Sci Rep
2025
Identification of plasma proteins associated with seizures in epilepsy: A consensus machine learning approach.
Ashtiani SH et al.·PLoS One
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools