TGFB3
transforming growth factor beta 3, the group of Transforming growth factor beta family
Basic information
Region (hg38): 14:75958096-75983011
Previous symbols: [ "ARVD1", "ARVD" ]
Links
Phenotypes
GenCC
Source:
- Rienhoff syndrome (Definitive), mode of inheritance: AD
- Rienhoff syndrome (Strong), mode of inheritance: AD
- Rienhoff syndrome (Strong), mode of inheritance: AD
- familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 1 (Limited), mode of inheritance: AD
- Rienhoff syndrome (Moderate), mode of inheritance: AD
- Loeys-Dietz syndrome (Limited), mode of inheritance: AR
- Rienhoff syndrome (Strong), mode of inheritance: AD
- Rienhoff syndrome (Strong), mode of inheritance: AD
- familial thoracic aortic aneurysm and aortic dissection (Limited), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Arrhythmogenic right ventricular dysplasia, familial 1; Loeys-Dietz syndrome 5 (Reinhoff syndrome) | AD | Cardiovascular | Individuals with Arrhythmogenic right ventricular dysplasia may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; Individuals with Loeys-Dietz syndrome 5 (Reinhoff syndrome) have been described with cardiovascular anomalies including structural abnormalities and aortic aneurysms as well as arrhythmia, and awareness may allow early management | Cardiovascular; Craniofacial; Musculoskeletal | 1572740; 12529708; 15639475; 19362677; 20301310; 23824657; 24798638; 25835445 |
ClinVar
This is a list of variants' phenotypes submitted to
- Rienhoff syndrome (357 variants)
- Familial thoracic aortic aneurysm and aortic dissection (189 variants)
- not provided (174 variants)
- not specified (39 variants)
- Rienhoff syndrome;Arrhythmogenic right ventricular dysplasia 1 (24 variants)
- Arrhythmogenic right ventricular cardiomyopathy (12 variants)
- TGFB3-related condition (12 variants)
- Arrhythmogenic right ventricular dysplasia 1 (9 variants)
- Arrhythmogenic right ventricular dysplasia 1;Rienhoff syndrome (9 variants)
- Loeys-Dietz syndrome 4 (5 variants)
- Inborn genetic diseases (4 variants)
- Long QT syndrome (3 variants)
- See cases (2 variants)
- Hypertrophic cardiomyopathy (2 variants)
- Cranioectodermal dysplasia (2 variants)
- Brugada syndrome (1 variants)
- Cardiomyopathy (1 variants)
- Flexion contracture (1 variants)
- Primary dilated cardiomyopathy (1 variants)
- Developmental disorder (1 variants)
- TGFB3-related connective tissue disorders (1 variants)
- Left ventricular noncompaction (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGFB3 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 | 109 | 113 | ||||
| missense | 238 | 248 | ||||
| nonsense | 15 | |||||
| start loss | 2 | |||||
| frameshift | 16 | 26 | ||||
| inframe indel | 5 | |||||
| splice donor/acceptor (+/-2bp) | 11 | |||||
| splice region ? | 6 | 15 | 1 | 22 | ||
| non coding ? | 12 | 56 | 12 | 80 | ||
| Total | 24 | 33 | 261 | 169 | 13 |
Variants in TGFB3
This is a list of pathogenic ClinVar variants found in the TGFB3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-75958363-A-G | Likely benign (Jun 19, 2018) | |||
| 14-75958367-C-T | Likely benign (Jun 14, 2018) | |||
| 14-75958491-A-G | Benign (Jun 18, 2018) | |||
| 14-75958505-C-T | Likely benign (Jun 26, 2018) | |||
| 14-75958521-T-C | Benign (Jun 18, 2018) | |||
| 14-75958674-T-C | Collapse (finding);Premature ventricular contraction | Uncertain significance (Jun 06, 2014) | ||
| 14-75958682-C-T | Uncertain significance (Mar 24, 2023) | |||
| 14-75958691-C-T | Likely benign (Sep 14, 2023) | |||
| 14-75958692-G-A | Arrhythmogenic right ventricular dysplasia 1 • Rienhoff syndrome • TGFB3-related disorder | Uncertain significance (Nov 21, 2023) | ||
| 14-75958704-TA-T | Benign (Aug 08, 2019) | |||
| 14-75958932-G-A | Likely benign (Jun 14, 2018) | |||
| 14-75959002-G-A | Arrhythmogenic right ventricular cardiomyopathy | Uncertain significance (Jun 14, 2016) | ||
| 14-75959174-C-T | Likely benign (Sep 26, 2017) | |||
| 14-75959178-C-T | not specified • Familial thoracic aortic aneurysm and aortic dissection | Benign/Likely benign (Feb 07, 2017) | ||
| 14-75959179-G-A | not specified | Conflicting classifications of pathogenicity (Mar 12, 2024) | ||
| 14-75959189-A-G | Rienhoff syndrome | Uncertain significance (Oct 05, 2023) | ||
| 14-75959190-G-A | Rienhoff syndrome | Likely benign (Jul 08, 2023) | ||
| 14-75959190-G-C | Rienhoff syndrome | Uncertain significance (Dec 12, 2023) | ||
| 14-75959195-A-C | Familial thoracic aortic aneurysm and aortic dissection | Uncertain significance (Nov 06, 2020) | ||
| 14-75959196-T-C | Familial thoracic aortic aneurysm and aortic dissection • Rienhoff syndrome | Likely benign (Dec 11, 2023) | ||
| 14-75959199-A-G | Familial thoracic aortic aneurysm and aortic dissection | Likely benign (Nov 08, 2023) | ||
| 14-75959200-C-T | Rienhoff syndrome | Pathogenic (Aug 01, 2013) | ||
| 14-75959204-A-G | Uncertain significance (May 04, 2023) | |||
| 14-75959205-C-G | Familial thoracic aortic aneurysm and aortic dissection • Rienhoff syndrome | Uncertain significance (Aug 05, 2022) | ||
| 14-75959205-C-T | not specified | Likely benign (Jul 17, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TGFB3 | protein_coding | protein_coding | ENST00000238682 | 7 | 24893 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.987 | 0.0127 | 125746 | 0 | 2 | 125748 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 162 | 233 | 0.694 | 0.0000152 | 2713 |
| Missense in Polyphen | 51 | 95.197 | 0.53573 | 1109 | ||
| Synonymous | -1.33 | 110 | 93.6 | 1.18 | 0.00000565 | 810 |
| Loss of Function | 3.67 | 1 | 17.6 | 0.0568 | 9.55e-7 | 214 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000578 | 0.0000578 |
| 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 | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively. {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.; FUNCTION: Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity). 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-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 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-3 and maintain it in a latent state during storage in extracellular milieus (By similarity). TGF-beta-3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3 (By similarity). Once activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity). {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P17125}.;
- Disease
- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 1 (ARVD1) [MIM:107970]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269|PubMed:15639475}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Loeys-Dietz syndrome 5 (LDS5) [MIM:615582]: A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS5 additional variable features include mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity. LDS5 patients do not manifest remarkable aortic or arterial tortuosity, and there is no strong evidence for early aortic dissection. {ECO:0000269|PubMed:23824657}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- 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);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Rheumatoid arthritis - 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;Differentiation Pathway;Extracellular vesicle-mediated signaling in recipient cells;Photodynamic therapy-induced HIF-1 survival signaling;Hypothetical Craniofacial Development Pathway;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;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;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;ALK1 signaling events;Glypican 1 network;TGF-beta receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.784
Intolerance Scores
- loftool
- 0.118
- rvis_EVS
- -0.6
- rvis_percentile_EVS
- 17.75
Haploinsufficiency Scores
- pHI
- 0.760
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.518
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tgfb3
- Phenotype
- vision/eye phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; normal 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); 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; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- tgfb3
- Affected structure
- ventral wall of dorsal aorta
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- activation of MAPK activity;response to hypoxia;in utero embryonic development;platelet degranulation;transforming growth factor beta receptor signaling pathway;salivary gland morphogenesis;female pregnancy;aging;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of signaling receptor 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 bone mineralization;negative regulation of transforming growth factor beta receptor signaling pathway;mammary gland development;response to progesterone;positive regulation of collagen biosynthetic process;response to laminar fluid shear stress;wound healing;regulation of cell population proliferation;odontogenesis;uterine wall breakdown;regulation of apoptotic process;positive regulation of apoptotic process;regulation of MAPK cascade;negative regulation of neuron apoptotic process;response to estrogen;ossification involved in bone remodeling;cell-cell junction organization;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;lung alveolus development;cell development;digestive tract development;embryonic neurocranium morphogenesis;inner ear development;positive regulation of protein secretion;positive regulation of filopodium assembly;positive regulation of stress fiber assembly;positive regulation of cell division;face morphogenesis;frontal suture morphogenesis;positive regulation of SMAD protein signal transduction;SMAD protein signal transduction;secondary palate development;detection of hypoxia;negative regulation of vascular smooth muscle cell proliferation;regulation of epithelial to mesenchymal transition involved in endocardial cushion formation;positive regulation of tight junction disassembly
- Cellular component
- extracellular region;extracellular space;nucleus;plasma membrane;cell surface;T-tubule;platelet alpha granule lumen;neuronal cell body;intracellular membrane-bounded organelle;collagen-containing extracellular matrix
- Molecular function
- type II transforming growth factor beta receptor binding;cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity;type I transforming growth factor beta receptor binding;type III transforming growth factor beta receptor binding;identical protein binding;protein heterodimerization activity;transforming growth factor beta binding