LTBP2

latent transforming growth factor beta binding protein 2, the group of Latent transforming growth factor beta binding proteins

Basic information

Region (hg38): 14:74498183-74612378

Previous symbols: [ "LTBP3", "C14orf141" ]

Links

ENSG00000119681 ∙ NCBI:4053 ∙ OMIM:602091 ∙ HGNC:6715 ∙ Uniprot:Q14767 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma (Definitive), mode of inheritance: AR
• Weill-Marchesani syndrome 3 (Moderate), mode of inheritance: AR
• microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma (Moderate), mode of inheritance: AR
• Weill-Marchesani syndrome (Supportive), mode of inheritance: AD
• congenital glaucoma (Supportive), mode of inheritance: AD
• glaucoma secondary to spherophakia/ectopia lentis and megalocornea (Supportive), mode of inheritance: AR
• glaucoma 3, primary congenital, D (Strong), mode of inheritance: AR
• microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma (Strong), mode of inheritance: AR
• Weill-Marchesani syndrome 3 (Limited), mode of inheritance: Unknown
• glaucoma 3, primary congenital, D (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glaucoma 3, primary congenital, D; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma; Weill-Marchesani syndrome 3	AR	Cardiovascular; Ophthalmologic; Pharmacogenomic	Surveillance, early diagnosis, and treatment of manifestations such as ectopia lentis and glaucoma with surgical interventions (with the use of pre and postoperative agents to control intraocular pressure), or, if surgery is not effective, drainage implants or cyclodestruction, may be effective to decrease morbidity and mortality related to vision loss; Individuals with cardiovascular manifestations including pulmonary and aortic stenosis have been described, and awareness may allow early diagnosis and treatment; Agents that may contribute to glaucoma, as well as alpha-2-agonists, should be avoided	Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic	18776954; 19361779; 19656777; 20179738; 20301293; 20301314; 20617341; 21081970; 22025892; 22539340; 23401661

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LTBP2 gene.

• not provided (26 variants)
• Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma (2 variants)
• Glaucoma 3, primary congenital, D (1 variants)
• Microspherophakia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LTBP2 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			8	293	10	311
missense		1	492	8	9	510
nonsense	4	2				6
start loss			1			1
frameshift	20	1	2			23
inframe indel	1		5			6
splice donor/acceptor (+/-2bp)	2	13				15
splice region		1	16	32	1	50
non coding			51	145	78	274
Total	27	17	559	446	97

Highest pathogenic variant AF is 0.0000132

Variants in LTBP2

This is a list of pathogenic ClinVar variants found in the LTBP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-74498200-T-C		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Conflicting classifications of pathogenicity (Jul 01, 2023)
14-74498315-C-T		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Uncertain significance (Jan 12, 2018)
14-74498421-C-A		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Benign/Likely benign (May 21, 2021)
14-74498465-G-A		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
14-74498521-T-C		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
14-74498531-A-G		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
14-74498618-C-T		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
14-74498648-G-A		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Uncertain significance (Jan 13, 2018)
14-74498731-A-G		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Benign/Likely benign (May 25, 2021)
14-74498772-C-T		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
14-74498840-C-T		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Benign/Likely benign (Jan 12, 2018)
14-74498858-A-G		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Uncertain significance (Jan 12, 2018)
14-74498927-T-C		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Benign (Jan 12, 2018)
14-74499011-G-C		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Benign/Likely benign (Jan 13, 2018)
14-74499066-G-A		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Benign (Jan 13, 2018)
14-74499107-T-C		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Uncertain significance (Jan 13, 2018)
14-74499108-G-A		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
14-74499141-G-A		Weill-Marchesani syndrome • Primary congenital glaucoma	Uncertain significance (Jun 14, 2016)
14-74499253-G-A		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Uncertain significance (Jan 12, 2018)
14-74499363-A-AAAC		Weill-Marchesani syndrome • Primary congenital glaucoma	Uncertain significance (Jun 14, 2016)
14-74499403-G-A		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
14-74499457-T-C		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Conflicting classifications of pathogenicity (Jan 13, 2018)
14-74499491-A-G		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
14-74499582-C-G		Weill-Marchesani syndrome • Glaucoma 3, primary congenital, D	Uncertain significance (Jan 13, 2018)
14-74499582-C-T		Glaucoma 3, primary congenital, D • Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LTBP2	protein_coding	protein_coding	ENST00000261978	36	114434

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000741	0.999	125677	1	70	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.189	1061	1.08e+3	0.984	0.0000704	11768
Missense in Polyphen		383	430.36	0.88994		4834
Synonymous	-1.76	509	461	1.10	0.0000335	3632
Loss of Function	6.33	24	88.1	0.272	0.00000423	1026

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000948	0.000947
Ashkenazi Jewish	0.000106	0.0000992
East Asian	0.0000549	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000317	0.000308
Middle Eastern	0.0000549	0.0000544
South Asian	0.000294	0.000294
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play an integral structural role in elastic-fiber architectural organization and/or assembly. {ECO:0000303|PubMed:10743502, ECO:0000303|PubMed:11104663}.
• Disease: DISEASE: Glaucoma 3, primary congenital, D (GLC3D) [MIM:613086]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:19361779}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma (MSPKA) [MIM:251750]: A rare disease characterized by smaller and more spherical lenses than normal bilaterally, an increased anteroposterior thickness of the lens, and highly myopic eyes. Lens dislocation or subluxation may occur, leading to defective accommodation. {ECO:0000269|PubMed:20617341}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Weill-Marchesani syndrome 3 (WMS3) [MIM:614819]: A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma. {ECO:0000269|PubMed:22539340}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation (Consensus)

Recessive Scores

• pRec: 0.0915

Intolerance Scores

• loftool: 0.0599
• rvis_EVS: -1.55
• rvis_percentile_EVS: 3.29

Haploinsufficiency Scores

• pHI: 0.343
• hipred: N
• hipred_score: 0.414
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.521

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ltbp2
• Phenotype: vision/eye phenotype; hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: protein targeting;transforming growth factor beta receptor signaling pathway;protein secretion;supramolecular fiber organization
• Cellular component: extracellular region;extracellular space;cell;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding;heparin binding;growth factor binding