ENG
endoglin, the group of CD molecules
Basic information
Region (hg38): 9:127815012-127854658
Previous symbols: [ "ORW1", "ORW" ]
Links
Phenotypes
GenCC
Source:
- telangiectasia, hereditary hemorrhagic, type 1 (Strong), mode of inheritance: AD
- hereditary hemorrhagic telangiectasia (Supportive), mode of inheritance: AD
- juvenile polyposis syndrome (Limited), mode of inheritance: AD
- telangiectasia, hereditary hemorrhagic, type 1 (Definitive), mode of inheritance: AD
- telangiectasia, hereditary hemorrhagic, type 1 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hereditary hemorrhagic telangiectasia, type 1 | AD | Hematologic | Individuals may have a variety of vascular complications, such as arteriovenous malformations (eg, pulmonary arteriovenous malformations, which can lead to a number of complications, including cerebral abscesses) and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality | Cardiovascular; Gastrointestinal; Hematologic | 5656734; 4834927; 4050544; 3186989; 2658618; 2729347; 2036743; 1518020; 7894484; 7666879; 9354504; 9541302; 9753031; 10636073; 11006369; 12920067; 15024723; 16287957; 16470787; 16752392; 16155196; 16542389; 17204053; 18831062; 18312453; 19439755; 20301525; 23380110; 23440993; 23722869; 23919827; 23962120; 24001356 |
| Oncologic complications have been reported (in Juvenile polyposis syndrome), but the evidence appears overall unclear |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary hemorrhagic telangiectasia (998 variants)
- Cardiovascular phenotype (386 variants)
- Telangiectasia, hereditary hemorrhagic, type 1 (307 variants)
- not provided (242 variants)
- not specified (70 variants)
- ENG-related condition (18 variants)
- Inborn genetic diseases (14 variants)
- Haemorrhagic telangiectasia 1 (6 variants)
- Juvenile Polyposis (5 variants)
- See cases (4 variants)
- Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia (3 variants)
- Pulmonary arterial hypertension (3 variants)
- ENG-Related Disorders (2 variants)
- Pulmonary hypertension, primary, 1 (2 variants)
- Telangiectasia, hereditary hemorrhagic, type 1;Systemic lupus erythematosus (1 variants)
- Cerebral arteriovenous malformation (1 variants)
- Moyamoya disease 2 (1 variants)
- Spontaneous, recurrent epistaxis (1 variants)
- Interstitial pneumonitis (1 variants)
- Galloway-Mowat syndrome 1 (1 variants)
- Telangiectasia of the skin;Palate telangiectasia;Spontaneous, recurrent epistaxis;Oral cavity telangiectasia;Pulmonary arteriovenous malformation (1 variants)
- Pulmonary arterial hypertension associated with congenital heart disease (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENG 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 | 188 | 197 | ||||
| missense | 15 | 49 | 258 | 77 | 13 | 412 |
| nonsense | 76 | 79 | ||||
| start loss | 7 | |||||
| frameshift | 206 | 13 | 220 | |||
| inframe indel | 20 | 26 | ||||
| splice donor/acceptor (+/-2bp) | 49 | 18 | 68 | |||
| splice region ? | 4 | 16 | 23 | 34 | 1 | 78 |
| non coding ? | 54 | 99 | 26 | 183 | ||
| Total | 356 | 90 | 340 | 364 | 42 |
Highest pathogenic variant AF is 0.00000668
Variants in ENG
This is a list of pathogenic ClinVar variants found in the ENG region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-127815096-G-A | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Apr 27, 2017) | ||
| 9-127815124-T-C | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jan 13, 2018) | ||
| 9-127815148-G-A | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815149-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815152-A-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815159-T-C | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jan 12, 2018) | ||
| 9-127815190-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jan 13, 2018) | ||
| 9-127815191-G-A | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jan 13, 2018) | ||
| 9-127815213-CAGTT-C | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jun 14, 2016) | ||
| 9-127815233-G-C | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jan 12, 2018) | ||
| 9-127815244-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 12, 2018) | ||
| 9-127815251-A-C | Benign (Jun 01, 2022) | |||
| 9-127815258-C-G | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815291-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 12, 2018) | ||
| 9-127815362-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Benign (Jan 12, 2018) | ||
| 9-127815409-T-G | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 12, 2018) | ||
| 9-127815416-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815430-G-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815532-G-T | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 12, 2018) | ||
| 9-127815549-G-A | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Jan 13, 2018) | ||
| 9-127815573-G-A | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815678-G-A | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Jan 13, 2018) | ||
| 9-127815682-C-T | Telangiectasia, hereditary hemorrhagic, type 1 | Likely benign (Aug 16, 2019) | ||
| 9-127815689-A-G | Telangiectasia, hereditary hemorrhagic, type 1 | Uncertain significance (Oct 19, 2022) | ||
| 9-127815697-G-T | Cardiovascular phenotype | Likely benign (Feb 23, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ENG | protein_coding | protein_coding | ENST00000373203 | 15 | 39745 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00142 | 125743 | 0 | 4 | 125747 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.935 | 338 | 390 | 0.867 | 0.0000235 | 4238 |
| Missense in Polyphen | 65 | 115.24 | 0.56403 | 1363 | ||
| Synonymous | -0.252 | 174 | 170 | 1.02 | 0.0000112 | 1370 |
| Loss of Function | 4.78 | 3 | 32.3 | 0.0929 | 0.00000177 | 335 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000353 | 0.0000353 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000932 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (PubMed:7894484). Regulates the migration of vascular endothelial cells (PubMed:17540773). Required for normal extraembryonic angiogenesis and for embryonic heart development (By similarity). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (By similarity). May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors (PubMed:1692830). Acts as TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors (PubMed:8370410, PubMed:21737454, PubMed:22347366, PubMed:23300529). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (PubMed:21737454, PubMed:22347366, PubMed:23300529). {ECO:0000250|UniProtKB:Q63961, ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:21737454, ECO:0000269|PubMed:23300529, ECO:0000269|PubMed:7894484, ECO:0000269|PubMed:8370410, ECO:0000305|PubMed:1692830}.;
- Disease
- DISEASE: Telangiectasia, hereditary hemorrhagic, 1 (HHT1) [MIM:187300]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269|PubMed:10545596, ECO:0000269|PubMed:10625079, ECO:0000269|PubMed:10982033, ECO:0000269|PubMed:15024723, ECO:0000269|PubMed:15712270, ECO:0000269|PubMed:16525724, ECO:0000269|PubMed:16752392, ECO:0000269|PubMed:20414677, ECO:0000269|PubMed:7894484, ECO:0000269|PubMed:9157574, ECO:0000269|PubMed:9245986, ECO:0000269|PubMed:9554745}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;TGF-beta Receptor Signaling;TGF_beta_Receptor;ALK1 signaling events;HIF-1-alpha transcription factor network
(Consensus)
Recessive Scores
- pRec
- 0.766
Intolerance Scores
- loftool
- 0.0316
- rvis_EVS
- -0.39
- rvis_percentile_EVS
- 27.03
Haploinsufficiency Scores
- pHI
- 0.150
- hipred
- Y
- hipred_score
- 0.594
- ghis
- 0.518
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.779
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Eng
- Phenotype
- growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype; craniofacial 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); 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; digestive/alimentary 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);
Gene ontology
- Biological process
- chronological cell aging;branching involved in blood vessel morphogenesis;vasculogenesis;positive regulation of protein phosphorylation;heart looping;sprouting angiogenesis;outflow tract septum morphogenesis;epithelial to mesenchymal transition involved in endocardial cushion formation;endocardial cushion morphogenesis;cardiac ventricle morphogenesis;cardiac atrium morphogenesis;ventricular trabecula myocardium morphogenesis;cell migration involved in endocardial cushion formation;regulation of transcription, DNA-templated;cell adhesion;negative regulation of gene expression;regulation of cardiac muscle cell apoptotic process;positive regulation of pathway-restricted SMAD protein phosphorylation;regulation of transforming growth factor beta receptor signaling pathway;central nervous system vasculogenesis;negative regulation of cell migration;BMP signaling pathway;positive regulation of BMP signaling pathway;negative regulation of protein autophosphorylation;response to corticosteroid;positive regulation of collagen biosynthetic process;dorsal aorta morphogenesis;response to drug;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;smooth muscle tissue development;artery morphogenesis;venous blood vessel morphogenesis;positive regulation of protein kinase B signaling;atrial cardiac muscle tissue morphogenesis;bone development;extracellular matrix constituent secretion;cellular response to mechanical stimulus;response to transforming growth factor beta;endocardial cushion to mesenchymal transition;vascular smooth muscle cell development;positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation;positive regulation of vascular smooth muscle cell differentiation;atrioventricular canal morphogenesis;regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis;regulation of cell proliferation involved in heart morphogenesis
- Cellular component
- extracellular space;focal adhesion;external side of plasma membrane;integral component of membrane;receptor complex;endothelial microparticle
- Molecular function
- transmembrane signaling receptor activity;transforming growth factor beta receptor, cytoplasmic mediator activity;type II transforming growth factor beta receptor binding;protein binding;galactose binding;glycosaminoglycan binding;type I transforming growth factor beta receptor binding;BMP binding;identical protein binding;protein homodimerization activity;activin binding;transforming growth factor beta binding