LTBP3

latent transforming growth factor beta binding protein 3, the group of Latent transforming growth factor beta binding proteins

Basic information

Region (hg38): 11:65538559-65558930

Previous symbols: [ "LTBP2" ]

Links

ENSG00000168056

∙ NCBI:4054 ∙ OMIM:602090 ∙ HGNC:6716 ∙ Uniprot:Q9NS15 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

brachyolmia-amelogenesis imperfecta syndrome (Definitive), mode of inheritance: AR
geleophysic dysplasia 3 (Limited), mode of inheritance: AD
brachyolmia-amelogenesis imperfecta syndrome (Limited), mode of inheritance: AR
Acromicric dysplasia (Supportive), mode of inheritance: AD
geleophysic dysplasia (Supportive), mode of inheritance: AD
brachyolmia-amelogenesis imperfecta syndrome (Supportive), mode of inheritance: AR
brachyolmia-amelogenesis imperfecta syndrome (Strong), mode of inheritance: AR
geleophysic dysplasia 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Geleophysic dysplasia 3; Dental anomalies and short stature	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Musculoskeletal	19344874; 25669657; 25899461; 27068007

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LTBP3 gene.

Brachyolmia-amelogenesis_imperfecta_syndrome (1315 variants)
Inborn_genetic_diseases (794 variants)
not_provided (77 variants)
LTBP3-related_disorder (58 variants)
Geleophysic_dysplasia_3 (19 variants)
not_specified (7 variants)
Heritable_Thoracic_Aortic_Disease (3 variants)
Amelogenesis_imperfecta (1 variants)
Intellectual_disability (1 variants)
Geleophysic_dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LTBP3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001130144.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			17 clinvar	486 clinvar	5 clinvar	508
missense	2 clinvar	3 clinvar	792 clinvar	21 clinvar		818
nonsense	10 clinvar	2 clinvar	4 clinvar			16
start loss						0
frameshift	35 clinvar	8 clinvar	4 clinvar			47
splice donor/acceptor (+/-2bp)	3 clinvar	22 clinvar	1 clinvar			26
Total	50	35	818	507	5

Highest pathogenic variant AF is 0.000236678

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LTBP3	protein_coding	protein_coding	ENST00000301873	28	20126

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.686	0.314	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.85	553	776	0.712	0.0000489	8339
Missense in Polyphen		162	287.77	0.56294		3044
Synonymous	0.892	316	337	0.938	0.0000239	2553
Loss of Function	5.89	14	65.4	0.214	0.00000303	743

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000188	0.000181
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.000170	0.000163
Finnish	0.000275	0.000231
European (Non-Finnish)	0.000216	0.000211
Middle Eastern	0.000170	0.000163
South Asian	0.0000681	0.0000653
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency- associated peptide (LAP), which is the regulatory chain of TGF- beta, and regulates integrin-dependent activation of TGF-beta. {ECO:0000303|PubMed:10743502, ECO:0000303|PubMed:11104663}.;
Disease: DISEASE: Dental anomalies and short stature (DASS) [MIM:601216]: A disorder characterized by hypoplastic amelogenesis imperfecta, significant short stature, brachyolmia-like anomalies including platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Dental anomalies include widely spaced, small, yellow teeth, oligodontia, and severely reduced to absent enamel. {ECO:0000269|PubMed:19344874}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Geleophysic dysplasia 3 (GPHYSD3) [MIM:617809]: A form of geleophysic dysplasia, a rare skeletal disease characterized by severe short stature, short hands and feet, and joint limitations. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include skin thickening, progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. GPHYSD3 inheritance is autosomal dominant. {ECO:0000269|PubMed:27068007}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation (Consensus)

Recessive Scores

pRec: 0.128

Intolerance Scores

loftool: 0.0559
rvis_EVS: -0.93
rvis_percentile_EVS: 9.61

Haploinsufficiency Scores

pHI: 0.304
hipred: Y
hipred_score: 0.655
ghis: 0.677

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.646

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ltbp3
Phenotype: vision/eye phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; craniofacial phenotype;

Zebrafish Information Network

Gene name: ltbp3
Affected structure: pharyngeal vasculature
Phenotype tag: abnormal
Phenotype quality: malformed

Gene ontology

Biological process: transforming growth factor beta activation;positive regulation of mesenchymal stem cell proliferation;positive regulation of mesenchymal stem cell differentiation
Cellular component: extracellular region;collagen-containing extracellular matrix;extracellular exosome
Molecular function: calcium ion binding;transforming growth factor beta binding