TGFB2

transforming growth factor beta 2, the group of Transforming growth factor beta family

Basic information

Region (hg38): 1:218345336-218444619

Links

ENSG00000092969 ∙ NCBI:7042 ∙ OMIM:190220 ∙ HGNC:11768 ∙ Uniprot:P61812 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Loeys-Dietz syndrome 4 (Strong), mode of inheritance: AD
• Loeys-Dietz syndrome 4 (Strong), mode of inheritance: AD
• Loeys-Dietz syndrome 4 (Strong), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
• Loeys-Dietz syndrome 4 (Strong), mode of inheritance: AD
• Loeys-Dietz syndrome 4 (Definitive), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Loeys-Dietz syndrome, type 4	AD	Cardiovascular	Individuals may manifest with cardiovascular anomalies, including thoracic aortic aneurysm as well as cardiac valvular anomalies, and awareness may allow early diagnosis and preventive measures and medical management in order to decrease morbidity and mortality	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal	20301312; 22772371; 22772368
Though manifestations may occur primarily in adults, surveillance in the pediatric period may be indicated

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TGFB2 gene.

• Loeys-Dietz syndrome 4 (37 variants)
• not provided (10 variants)
• Familial thoracic aortic aneurysm and aortic dissection (7 variants)
• Ehlers-Danlos syndrome (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGFB2 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			2	123		125
missense	1	11	222	5		239
nonsense	16	7	3			26
start loss						0
frameshift	31	8	2			41
inframe indel			6			6
splice donor/acceptor (+/-2bp)	2	10				12
splice region			6	8	3	17
non coding			66	60	34	160
Total	50	36	301	188	34

Highest pathogenic variant AF is 0.00000657

Variants in TGFB2

This is a list of pathogenic ClinVar variants found in the TGFB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-218345400-A-G		Loeys-Dietz syndrome 4	Benign/Likely benign (Jun 14, 2018)
1-218345420-T-TAGAAAG		Loeys-Dietz syndrome • Loeys-Dietz syndrome 4	Uncertain significance (Aug 27, 2021)
1-218345431-A-G		Loeys-Dietz syndrome 4	Uncertain significance (Jan 12, 2018)
1-218345453-G-A		Loeys-Dietz syndrome 4	Uncertain significance (Jan 12, 2018)
1-218345465-G-C		Loeys-Dietz syndrome 4	Uncertain significance (Jan 12, 2018)
1-218345472-G-A		Loeys-Dietz syndrome 4	Benign/Likely benign (Jun 14, 2018)
1-218345549-G-T		Loeys-Dietz syndrome 4	Uncertain significance (Jan 12, 2018)
1-218345686-C-T		Loeys-Dietz syndrome 4	Likely benign (Apr 27, 2017)
1-218345908-T-C		Loeys-Dietz syndrome 4	Uncertain significance (Jan 12, 2018)
1-218345918-A-C		Loeys-Dietz syndrome 4	Benign (Nov 26, 2019)
1-218345944-G-C		Loeys-Dietz syndrome 4	Uncertain significance (Jan 13, 2018)
1-218345956-G-T		Loeys-Dietz syndrome 4	Benign (Jan 13, 2018)
1-218345988-A-C		Loeys-Dietz syndrome 4	Benign (Apr 27, 2017)
1-218346003-A-C		Loeys-Dietz syndrome 4	Uncertain significance (Sep 15, 2021)
1-218346019-C-A		Loeys-Dietz syndrome 4	Uncertain significance (Jan 13, 2018)
1-218346020-C-G		Loeys-Dietz syndrome 4	Uncertain significance (Jan 13, 2018)
1-218346023-G-A		Loeys-Dietz syndrome 4	Uncertain significance (Sep 01, 2021)
1-218346025-T-C		Loeys-Dietz syndrome 4	Benign (Nov 26, 2019)
1-218346039-C-T		Loeys-Dietz syndrome 4	Uncertain significance (Jan 13, 2018)
1-218346048-G-GCGCACA		Loeys-Dietz syndrome • Loeys-Dietz syndrome 4	Uncertain significance (Feb 09, 2022)
1-218346052-A-ACACGCC		Loeys-Dietz syndrome	Uncertain significance (Jun 14, 2016)
1-218346056-G-A		Loeys-Dietz syndrome 4	Uncertain significance (Jan 13, 2018)
1-218346056-GCA-G		Loeys-Dietz syndrome	Likely benign (Jun 14, 2016)
1-218346056-G-GCA		Loeys-Dietz syndrome	Uncertain significance (Jun 14, 2016)
1-218346056-G-GCACA		Loeys-Dietz syndrome	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGFB2	protein_coding	protein_coding	ENST00000366929	8	98385

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000952	124655	0	1	124656	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.13	153	247	0.619	0.0000125	2903
Missense in Polyphen		39	98.372	0.39645		1127
Synonymous	-0.149	98	96.1	1.02	0.00000501	836
Loss of Function	4.16	0	20.1	0.00	9.15e-7	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000333	0.0000333
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transforming growth factor beta-2 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively. {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.; FUNCTION: Transforming growth factor beta-2: Multifunctional protein that regulates various processes such as angiogenesis and heart development (PubMed:22772371, PubMed:22772368). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains remain non-covalently linked rendering TGF-beta-2 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 and maintain it in a latent state during storage in extracellular milieus (By similarity). Once activated following release of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity). {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:22772368, ECO:0000269|PubMed:22772371}.
• Disease: DISEASE: Note=A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9. {ECO:0000269|PubMed:12706107}.; DISEASE: Loeys-Dietz syndrome 4 (LDS4) [MIM:614816]: An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae. {ECO:0000269|PubMed:22772368, ECO:0000269|PubMed:22772371}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in TGFB2 may be a cause of non-syndromic aortic disease (NSAD). NSAD is a frequently asymptomatic but potentially lethal disease characterized by thoracic aortic aneurysms and dissections without additional syndromic features. {ECO:0000269|PubMed:25046559}.
• Pathway: Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Cell cycle - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Tuberculosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);TGF-Core;Extracellular vesicle-mediated signaling in recipient cells;Vitamin D Receptor Pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;MAPK Signaling Pathway;p38 MAPK Signaling Pathway;Pathways in clear cell renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;EMT transition in Colorectal Cancer;Type 2 papillary renal cell carcinoma;Endochondral Ossification;signal transduction through il1r;alk in cardiac myocytes;nfkb activation by nontypeable hemophilus influenzae;ctcf: first multivalent nuclear factor;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Extracellular matrix organization;ATF-2 transcription factor network;Molecules associated with elastic fibres;Elastic fibre formation;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;TGF_beta_Receptor;tgf beta signaling pathway;Hemostasis;ECM proteoglycans;TGF-beta signaling TAK1;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;Regulation of retinoblastoma protein;Signaling events mediated by the Hedgehog family (Consensus)

Recessive Scores

• pRec: 0.876

Intolerance Scores

• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.647
• hipred: Y
• hipred_score: 0.851
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tgfb2
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; embryo phenotype; hematopoietic system 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); growth/size/body region phenotype; reproductive 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: tgfb2
• Affected structure: palate
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: cell morphogenesis;skeletal system development;angiogenesis;eye development;response to hypoxia;kidney development;epithelial to mesenchymal transition;neural tube closure;hair follicle development;platelet degranulation;heart morphogenesis;outflow tract septum morphogenesis;membranous septum morphogenesis;heart valve morphogenesis;atrioventricular valve morphogenesis;pulmonary valve morphogenesis;endocardial cushion morphogenesis;cardiac right ventricle morphogenesis;ventricular trabecula myocardium morphogenesis;endocardial cushion fusion;atrial septum primum morphogenesis;neural retina development;protein phosphorylation;cell cycle arrest;transforming growth factor beta receptor signaling pathway;cell-cell signaling;salivary gland morphogenesis;heart development;cell death;cell population proliferation;positive regulation of cell population proliferation;negative regulation of cell population proliferation;glial cell migration;male gonad development;response to wounding;embryo development ending in birth or egg hatching;cardioblast differentiation;regulation of signaling receptor activity;negative regulation of gene expression;positive regulation of epithelial cell migration;negative regulation of alkaline phosphatase activity;positive regulation of epithelial to mesenchymal transition;positive regulation of pathway-restricted SMAD protein phosphorylation;negative regulation of macrophage cytokine production;positive regulation of phosphatidylinositol 3-kinase signaling;cell migration;negative regulation of angiogenesis;hemopoiesis;collagen fibril organization;positive regulation of cell growth;negative regulation of cell growth;embryonic limb morphogenesis;neutrophil chemotaxis;hair follicle morphogenesis;activation of protein kinase activity;response to progesterone;positive regulation of stress-activated MAPK cascade;regulation of transforming growth factor beta2 production;positive regulation of cell adhesion mediated by integrin;ascending aorta morphogenesis;wound healing;regulation of cell population proliferation;dopamine biosynthetic process;odontogenesis;response to drug;uterine wall breakdown;regulation of apoptotic process;regulation of MAPK cascade;positive regulation of neuron apoptotic process;cell-cell junction organization;positive regulation of integrin biosynthetic process;positive regulation of Notch signaling pathway;positive regulation of ossification;positive regulation of cell cycle;positive regulation of heart contraction;negative regulation of Ras protein signal transduction;somatic stem cell division;cell development;embryonic digestive tract development;neuron development;generation of neurons;inner ear development;negative regulation of epithelial cell proliferation;positive regulation of protein secretion;negative regulation of immune response;positive regulation of immune response;positive regulation of cell division;regulation of timing of catagen;positive regulation of timing of catagen;positive regulation of cardioblast differentiation;cardiac muscle cell proliferation;uterus development;cardiac epithelial to mesenchymal transition;pathway-restricted SMAD protein phosphorylation;SMAD protein signal transduction;ventricular septum morphogenesis;atrial septum morphogenesis;pharyngeal arch artery morphogenesis;secondary palate development;extrinsic apoptotic signaling pathway;regulation of apoptotic process involved in outflow tract morphogenesis;positive regulation of pri-miRNA transcription by RNA polymerase II;regulation of complement-dependent cytotoxicity;substantia propria of cornea development;cranial skeletal system development;negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation;positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
• Cellular component: extracellular region;extracellular space;axon;platelet alpha granule lumen;neuronal cell body;collagen-containing extracellular matrix
• Molecular function: amyloid-beta binding;signaling receptor binding;type II transforming growth factor beta receptor binding;cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity;type III transforming growth factor beta receptor binding;protein homodimerization activity;protein heterodimerization activity