ACVRL1 (Activin A Receptor Like Type 1)
Key regulator of angiogenesis and vascular development; mutations cause hereditary hemorrhagic telangiectasia type 2 (HHT2).
Gene Information Card
| Symbol | ACVRL1 |
|---|---|
| Full Name | Activin A Receptor Like Type 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 94 ncbi.nlm.nih.gov/gene/94 |
| Ensembl ID | ENSG00000139567 |
| UniProt ID | P37023 |
| OMIM ID | 601284 |
| HGNC ID | 175 |
| Aliases | ALK1, HHT2, ACVRLK1, TSR-I |
Description
The ACVRL1 gene encodes activin A receptor like type 1 (ALK1), a type I receptor in the TGF-beta superfamily. ALK1 is predominantly expressed on endothelial cells and plays a critical role in angiogenesis by transducing signals from BMP9 and BMP10 ligands. Mutations in ACVRL1 cause hereditary hemorrhagic telangiectasia type 2 (HHT2), an autosomal dominant disorder characterized by vascular malformations, epistaxis, and telangiectasias.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary hemorrhagic telangiectasia type 2 (HHT2) | Loss-of-function mutations in ACVRL1 impair BMP9/BMP10 signaling, leading to abnormal angiogenesis and fragile blood vessels. | OMIM #601284; ClinVar; multiple peer-reviewed studies |
| Pulmonary arterial hypertension (PAH) | Rare missense variants in ACVRL1 disrupt endothelial BMP signaling, contributing to vascular remodeling. | ClinVar; NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.7 | Low |
| Brain | 2.1 | Not detected |
| Kidney | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 35.2 | High expression; primary endothelial model |
| HPAEC (pulmonary artery endothelial) | 28.9 | High expression |
| HEK293 | 1.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1120C>T (p.Arg374Trp) | Missense | Common in HHT2 | Loss of receptor function; impaired BMP9 binding |
| c.1231C>T (p.Arg411Trp) | Missense | Recurrent | Dominant-negative effect; reduced cell surface expression |
| c.1450C>T (p.Arg484Ter) | Nonsense | Rare | Premature truncation; complete loss of kinase domain |
Mutation functional classification
Loss of Function (LOF)
Most HHT2-associated mutations (nonsense, frameshift, splice-site) lead to haploinsufficiency or complete loss of ALK1 function.
Gain of Function (GOF)
Not reported for ACVRL1; gain-of-function mutations are not associated with HHT2.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg411Trp) produce a receptor that interferes with wild-type ALK1 signaling.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0005024 (transforming growth factor beta receptor activity |
| • type I) | • GO:0007179 (transforming growth factor beta receptor signaling pathway) |
| • GO:0001525 (angiogenesis) | • GO:0016021 (integral component of membrane) |
Pathways
• TGF-beta signaling pathway (KEGG: hsa04350)
• BMP signaling pathway (Reactome: R-HSA-201451)
• Signaling by TGF-beta family members (Reactome: R-HSA-9006936)
Protein Summary
ALK1 is a 503-amino acid transmembrane serine/threonine kinase receptor. It consists of an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular kinase domain. Upon binding BMP9 or BMP10, ALK1 phosphorylates SMAD1/5/8, which then complex with SMAD4 to regulate transcription of angiogenic genes. ALK1 is essential for endothelial cell proliferation, migration, and vessel maturation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACVRL1 Knockout HEK293 Cell Line | EDJ-KQ17795 | Human | 94 | Details Get a Quote |
| ACVRL1 Knockout HeLa Cell Line | EDJ-KQ52544 | Human | 94 | Details Get a Quote |
| ACVRL1 Knockout A-549 Cell Line | EDJ-KQ61028 | Human | 94 | Details Get a Quote |
| ACVRL1 Knockout HCT 116 Cell Line | EDJ-KQ69503 | Human | 94 | Details Get a Quote |
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