LTBP1

latent transforming growth factor beta binding protein 1, the group of Latent transforming growth factor beta binding proteins

Basic information

Region (hg38): 2:32946952-33399509

Links

ENSG00000049323 ∙ NCBI:4052 ∙ OMIM:150390 ∙ HGNC:6714 ∙ Uniprot:Q14766 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cutis laxa, autosomal recessive, type 2E (Limited), mode of inheritance: AR
• cutis laxa, autosomal recessive, type 2E (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cutis laxa, autosomal recessive, type IIE	AR	Cardiovascular	The condition may include congenital cardiovascular anomalies, and awareness may allow early identification and management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal	33991472

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LTBP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LTBP1 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				7	4	11
missense			119	6	6	131
nonsense		1				1
start loss						0
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region				1	3	4
non coding						0
Total	0	3	120	13	10

Variants in LTBP1

This is a list of pathogenic ClinVar variants found in the LTBP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-32947358-C-T		not specified	Uncertain significance (Apr 29, 2024)
2-32947364-G-A		not specified	Uncertain significance (Apr 15, 2024)
2-32947376-G-T		not specified	Uncertain significance (Jan 03, 2024)
2-32947412-T-C		not specified	Uncertain significance (Oct 16, 2023)
2-32947425-C-A		not specified	Uncertain significance (Oct 06, 2021)
2-32947453-G-T		not specified	Uncertain significance (Apr 25, 2023)
2-32947488-A-G		not specified	Uncertain significance (Jan 03, 2022)
2-32947503-C-A		not specified	Uncertain significance (Feb 15, 2023)
2-32947506-G-A		not specified	Uncertain significance (Jun 19, 2024)
2-32947527-C-T		not specified	Uncertain significance (Feb 15, 2023)
2-32947529-G-C		not specified	Uncertain significance (Jul 14, 2023)
2-32947578-G-T		not specified	Uncertain significance (May 16, 2022)
2-32947592-C-T		not specified	Uncertain significance (Nov 09, 2023)
2-32947599-G-A		not specified	Uncertain significance (Jan 26, 2022)
2-32947664-C-T		Congenital heart disease	Uncertain significance (Apr 23, 2021)
2-32947681-C-A		not specified	Uncertain significance (Feb 01, 2024)
2-32947683-C-T		not specified	Uncertain significance (Jun 03, 2024)
2-32947686-A-G		not specified	Uncertain significance (Aug 04, 2023)
2-32947709-G-C		not specified	Uncertain significance (Dec 06, 2022)
2-32947710-C-T		not specified	Uncertain significance (Jul 05, 2022)
2-32947716-T-TCAC			Uncertain significance (Sep 01, 2023)
2-32947736-G-C		not specified	Uncertain significance (Oct 03, 2022)
2-32947787-C-A		not specified	Uncertain significance (Jan 10, 2022)
2-32947796-C-T		not specified	Uncertain significance (Apr 25, 2023)
2-32948880-A-G		not specified	Uncertain significance (Nov 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LTBP1	protein_coding	protein_coding	ENST00000404816	34	452538

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.72e-9	1.00	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.172	909	924	0.984	0.0000506	11251
Missense in Polyphen		261	342.52	0.76201		4014
Synonymous	-2.47	416	357	1.17	0.0000215	3271
Loss of Function	5.71	32	90.8	0.353	0.00000468	1077

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000464	0.000464
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000232	0.000231
European (Non-Finnish)	0.000195	0.000193
Middle Eastern	0.000218	0.000217
South Asian	0.000299	0.000294
Other	0.00	0.00

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 (PubMed:2022183, PubMed:8617200, PubMed:8939931). 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 (PubMed:8617200, PubMed:8939931, PubMed:15184403). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (PubMed:22278742). {ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;TGF-beta Receptor Signaling;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.0115
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.47

Haploinsufficiency Scores

• pHI: 0.474
• hipred: N
• hipred_score: 0.418
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.494

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ltbp1
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; liver/biliary 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); 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); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype

Gene ontology

• Biological process: ventricular septum development;transmembrane receptor protein serine/threonine kinase signaling pathway;sequestering of TGFbeta in extracellular matrix;aorta development;post-translational protein modification;cellular protein metabolic process;coronary vasculature development;regulation of transforming growth factor beta activation
• Cellular component: microfibril;extracellular region;endoplasmic reticulum lumen;extracellular matrix;protein-containing complex;collagen-containing extracellular matrix
• Molecular function: transforming growth factor beta-activated receptor activity;extracellular matrix structural constituent;calcium ion binding;protein binding;transforming growth factor beta binding;microfibril binding