ENG Gene (Endoglin): Function, Expression, and Clinical Significance
A comprehensive overview of the ENG gene, its protein product endoglin, associated diseases, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | ENG |
|---|---|
| Full Name | Endoglin |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 2022 ncbi.nlm.nih.gov/gene/2022 |
| Ensembl ID | ENSG00000106991 |
| UniProt ID | P17813 |
| OMIM ID | 131195 |
| HGNC ID | 3349 |
| Aliases | CD105, END, HHT1, ORW1 |
Description
The ENG gene encodes endoglin (CD105), a homodimeric transmembrane glycoprotein that is a core component of the transforming growth factor-beta (TGF-beta) receptor complex. It is primarily expressed on endothelial cells and plays a critical role in angiogenesis, vascular remodeling, and cardiovascular development. Endoglin functions as an auxiliary receptor that modulates TGF-beta/ALK1 and TGF-beta/ALK5 signaling pathways. Mutations in ENG are the primary cause of Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disorder characterized by arteriovenous malformations and telangiectasias. Additionally, ENG expression is upregulated in tumor-associated vasculature, making it a significant biomarker and therapeutic target in oncology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) | Loss-of-function mutations in ENG lead to haploinsufficiency of endoglin, disrupting TGF-beta signaling in endothelial cells, which impairs vascular development and integrity, resulting in telangiectasias and arteriovenous malformations. | OMIM 131195; ClinVar |
| Pulmonary Arterial Hypertension (PAH) | Rare ENG mutations have been identified in patients with PAH, suggesting a role in vascular smooth muscle cell proliferation and endothelial dysfunction, contributing to pulmonary vascular remodeling. | OMIM 131195; NCBI Gene |
| Cancer (Tumor Angiogenesis) | ENG is overexpressed in proliferating endothelial cells of tumor vasculature. It promotes angiogenesis by modulating TGF-beta signaling, facilitating tumor growth and metastasis. It is a target for anti-angiogenic therapies. | COSMIC; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Adrenal Gland | 58.2 | Medium |
| Lung | 45.1 | Medium |
| Spleen | 38.5 | Medium |
| Heart | 35.9 | Medium |
| Liver | 25.4 | Low |
| Brain | 12.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HUVEC (Human Umbilical Vein Endothelial Cells) | High | Primary endothelial cells; high expression is expected due to the role of ENG in vascular biology. |
| HMVEC (Human Microvascular Endothelial Cells) | High | Microvascular endothelial cells; consistent with high expression in angiogenic tissues. |
| HeLa (Cervical Cancer) | Low | Epithelial cancer cell line; lower expression compared to endothelial cells. |
| MCF7 (Breast Cancer) | Low | Epithelial cancer cell line; expression is lower than in endothelial cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.360C>A (p.Cys120Ter) | Nonsense | Rare (pathogenic) | Introduces a premature stop codon, leading to a truncated non-functional protein, causing haploinsufficiency and HHT1. |
| c.479G>A (p.Arg160Gln) | Missense | Rare (pathogenic) | Amino acid substitution in the extracellular domain, likely disrupting ligand binding or protein folding, leading to HHT1. |
| c.1130_1131del (p.Gly377AlafsTer5) | Frameshift | Rare (pathogenic) | Deletion causing a frameshift and premature termination, resulting in a truncated protein and loss of function. |
| c.1471C>T (p.Arg491Trp) | Missense | Rare (pathogenic) | Substitution in the cytoplasmic domain, potentially affecting intracellular signaling interactions, associated with HHT1. |
Mutation functional classification
Loss of Function (LOF)
The majority of pathogenic ENG mutations are loss-of-function, leading to haploinsufficiency. This is the primary mechanism for HHT1, where reduced endoglin levels disrupt TGF-beta signaling and vascular integrity.
Gain of Function (GOF)
No clear gain-of-function mutations have been described for ENG in hereditary diseases. However, in cancer, overexpression of wild-type ENG is considered a pro-angiogenic factor, but this is not due to a mutation.
Dominant Negative (DN)
While most mutations cause haploinsufficiency, some missense mutations may exert a dominant-negative effect by forming non-functional heterodimers with the wild-type protein, further reducing functional endoglin levels.
View complete mutation data：
Gene Ontology (GO)
| • transmembrane signaling receptor activity | • transforming growth factor beta receptor activity |
| • protein homodimerization activity | • integrin binding |
| • cell adhesion molecule binding | • angiogenesis |
| • vasculogenesis | • transforming growth factor beta receptor signaling pathway |
| • cell migration | • cell-cell adhesion |
| • endothelial cell proliferation | • response to hypoxia |
| • plasma membrane | • integral component of membrane |
Pathways
• TGF-beta signaling pathway
• ALK1 signaling pathway
• Angiogenesis
• Endothelial cell differentiation
• VEGF signaling pathway (crosstalk)
Protein Summary
Endoglin (CD105) is a 180 kDa homodimeric transmembrane glycoprotein. It consists of a large extracellular domain (561 amino acids), a single transmembrane domain, and a short cytoplasmic tail (47 amino acids). It is a key auxiliary receptor for TGF-beta superfamily ligands, particularly BMP9 and BMP10, forming a complex with ALK1 (ACVRL1) and TGFBR2. This complex phosphorylates SMAD1/5/8, regulating endothelial cell proliferation, migration, and vascular tone. Endoglin is highly expressed on proliferating endothelial cells, syncytiotrophoblasts, and mesenchymal stem cells. Its expression is essential for embryonic cardiovascular development, as Eng knockout mice die mid-gestation due to vascular defects. In adults, it is a marker of activated endothelium and is upregulated during inflammation, wound healing, and tumor angiogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ENG Knockout HEK293 Cell Line | EDJ-KQ3346 | Human | 2022 | Details Get a Quote |
| ENGASE Knockout HEK293 Cell Line | EDJ-KQ12506 | Human | 64772 | Details Get a Quote |
| ENG Knockout HCT 116 Cell Line | EDJ-KQ24991 | Human | 2022 | Details Get a Quote |
| ENG Knockout HeLa Cell Line | EDJ-KQ24992 | Human | 2022 | Details Get a Quote |
| ENGASE Knockout A-549 Cell Line | EDJ-KQ42714 | Human | 64772 | Details Get a Quote |
| ENGASE Knockout HCT 116 Cell Line | EDJ-KQ42716 | Human | 64772 | Details Get a Quote |
| ENGASE Knockout HeLa Cell Line | EDJ-KQ42717 | Human | 64772 | Details Get a Quote |
| ENG Knockout A-549 Cell Line | EDJ-KQ61636 | Human | 2022 | Details Get a Quote |
