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 (28 variants)
• Geleophysic dysplasia 3 (2 variants)
• Heritable Thoracic Aortic Disease (1 variants)
• not provided (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	355	3	370
missense	1	1	577	9	2	590
nonsense	3	2	3			8
start loss						0
frameshift	24	4	2			30
inframe indel			21	2	2	25
splice donor/acceptor (+/-2bp)	1	15	1			17
splice region		1	21	57	4	83
non coding			2	160	31	193
Total	29	22	618	526	38

Highest pathogenic variant AF is 0.0000526

Variants in LTBP3

This is a list of pathogenic ClinVar variants found in the LTBP3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-65538885-G-A			Benign (Jun 20, 2021)
11-65539063-GGGCGGCGTC-G		LTBP3-related disorder	Likely benign (Dec 16, 2020)
11-65539073-GGCGGCGTCA-G		Brachyolmia-amelogenesis imperfecta syndrome	Conflicting classifications of pathogenicity (Jul 26, 2023)
11-65539080-T-A		Geleophysic dysplasia 3	Pathogenic (Aug 27, 2019)
11-65539082-A-AGCGGCGGCGCTGGGGAACGCAGGCCCCGTGCGG		Brachyolmia-amelogenesis imperfecta syndrome	Conflicting classifications of pathogenicity (May 17, 2024)
11-65539084-C-T		Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Nov 01, 2022)
11-65539085-G-A			Uncertain significance (Oct 02, 2019)
11-65539085-G-T		Inborn genetic diseases • Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Dec 17, 2021)
11-65539084-C-CGGCGGCGCTGGGGAACGCAGGCCCCGTGCG		Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Mar 09, 2022)
11-65539086-G-A		Brachyolmia-amelogenesis imperfecta syndrome	Likely benign (Jul 03, 2023)
11-65539087-C-A		Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Aug 21, 2022)
11-65539087-C-T		Brachyolmia-amelogenesis imperfecta syndrome • Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
11-65539089-G-C		Inborn genetic diseases • Brachyolmia-amelogenesis imperfecta syndrome	Likely benign (Nov 17, 2023)
11-65539090-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
11-65539092-C-G		Brachyolmia-amelogenesis imperfecta syndrome • LTBP3-related disorder	Uncertain significance (Dec 09, 2023)
11-65539095-G-A		Inborn genetic diseases	Likely benign (Jun 09, 2019)
11-65539096-G-A		Inborn genetic diseases	Uncertain significance (Dec 24, 2021)
11-65539105-G-A		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
11-65539106-C-T		Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Jul 06, 2023)
11-65539109-C-G		Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Nov 20, 2022)
11-65539110-G-A		Inborn genetic diseases	Likely benign (May 24, 2021)
11-65539112-G-T		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
11-65539114-G-A		Brachyolmia-amelogenesis imperfecta syndrome	Uncertain significance (Mar 18, 2023)
11-65539117-C-T		Brachyolmia-amelogenesis imperfecta syndrome • Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
11-65539122-G-A		Brachyolmia-amelogenesis imperfecta syndrome • Inborn genetic diseases	Likely benign (Dec 25, 2023)

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