ACVR1 Gene (Activin A Receptor Type 1): Function, Mutations, and Related Diseases
A comprehensive biomedical overview of the ACVR1 gene, including its genomic context, protein function, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | ACVR1 |
|---|---|
| Full Name | Activin A receptor type 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q23.2-q23.3 |
| NCBI Gene ID | 90 ncbi.nlm.nih.gov/gene/90 |
| Ensembl ID | ENSG00000115170 |
| UniProt ID | Q04771 |
| OMIM ID | 102576 |
| HGNC ID | 171 |
| Aliases | ALK2, ACVR1A, ACTRI, ACVRLK2, FOP, SKR1, TSRI |
Description
The ACVR1 gene encodes activin A receptor type 1 (ACVR1), also known as ALK2, a transmembrane serine/threonine kinase receptor that belongs to the TGF-beta receptor superfamily. It binds activins and bone morphogenetic proteins (BMPs) to regulate intracellular SMAD signaling, which is critical for bone formation, muscle development, and other developmental processes. Mutations in ACVR1 are strongly associated with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterized by heterotopic ossification. The gene is also implicated in certain cancers, including diffuse intrinsic pontine glioma (DIPG).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fibrodysplasia ossificans progressiva (FOP) | Gain-of-function mutations (e.g., R206H) in the ACVR1 kinase domain lead to constitutive activation or altered ligand specificity, causing aberrant BMP signaling and ectopic bone formation in soft tissues. | ClinVar, OMIM (102576), multiple publications |
| Diffuse intrinsic pontine glioma (DIPG) | Somatic mutations (e.g., R206H, G328V) in ACVR1 are found in ~20-30% of DIPG cases, leading to dysregulated BMP signaling that promotes tumor growth. | COSMIC, ClinVar, published studies |
| Congenital heart defects | Rare variants in ACVR1 have been reported in patients with congenital heart defects, though the mechanism is not fully defined. | ClinVar, limited evidence |
| Progressive osseous heteroplasia (POH) | Some cases of POH have been linked to ACVR1 mutations, but the association is less common than with GNAS mutations. | ClinVar, case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Lung | 7.1 | Low |
| Liver | 4.3 | Low |
| Kidney | 6.0 | Low |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.5 | High expression |
| A549 | 8.0 | Medium |
| MCF7 | 6.5 | Medium |
| K562 | 4.0 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R206H | Missense | ~97% of FOP cases | Gain-of-function: constitutive activation of the receptor, leading to aberrant BMP signaling |
| G328V | Missense | Somatic in DIPG | Gain-of-function: altered kinase activity, promotes tumorigenesis |
| G328R | Missense | Somatic in DIPG | Gain-of-function: similar to G328V |
| L196P | Missense | Rare in FOP | Gain-of-function: constitutive activation |
| Q207E | Missense | Rare in FOP | Gain-of-function: altered ligand specificity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ACVR1 are rare and not well characterized; they may lead to reduced BMP signaling, but no clear disease association has been established.
Gain of Function (GOF)
Most pathogenic mutations in ACVR1 are gain-of-function, leading to constitutive activation or altered ligand specificity, which is the primary mechanism in FOP and DIPG.
Dominant Negative (DN)
Dominant-negative effects have not been reported for ACVR1 mutations; the known mutations act as gain-of-function.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein serine/threonine kinase activity |
| • transmembrane receptor protein serine/threonine kinase activity | • BMP receptor activity |
| • activin receptor activity | • signal transduction |
| • SMAD protein signal transduction | • positive regulation of osteoblast differentiation |
| • cell surface receptor signaling pathway | • protein phosphorylation |
Pathways
• BMP signaling pathway
• TGF-beta signaling pathway
• Activin receptor signaling pathway
• SMAD signaling pathway
• Osteoblast differentiation
Protein Summary
The ACVR1 protein is a type I receptor for BMPs and activins. It consists of an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular serine/threonine kinase domain. Upon ligand binding, ACVR1 phosphorylates SMAD1/5/8, which then complex with SMAD4 and translocate to the nucleus to regulate gene transcription. This pathway is essential for bone and muscle development. Mutations that constitutively activate ACVR1 lead to excessive BMP signaling, causing heterotopic ossification in FOP and contributing to tumor growth in DIPG.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACVR1 Knockout HEK293 Cell Line | EDJ-KQ361 | Human | 90 | Details Get a Quote |
| ACVR1B Knockout HEK293 Cell Line | EDJ-KQ362 | Human | 91 | Details Get a Quote |
| ACVR1C Knockout HEK293 Cell Line | EDJ-KQ363 | Human | 130399 | Details Get a Quote |
| ACVR1B Knockout A-549 Cell Line | EDJ-KQ17978 | Human | 91 | Details Get a Quote |
| ACVR1 Knockout A-549 Cell Line | EDJ-KQ18548 | Human | 90 | Details Get a Quote |
| ACVR1 Knockout HCT 116 Cell Line | EDJ-KQ18549 | Human | 90 | Details Get a Quote |
| ACVR1 Knockout HeLa Cell Line | EDJ-KQ18550 | Human | 90 | Details Get a Quote |
| ACVR1B Knockout HCT 116 Cell Line | EDJ-KQ18551 | Human | 91 | Details Get a Quote |
| ACVR1B Knockout HeLa Cell Line | EDJ-KQ18552 | Human | 91 | Details Get a Quote |
| ACVR1C Knockout HeLa Cell Line | EDJ-KQ58277 | Human | 130399 | Details Get a Quote |
| ACVR1C Knockout A-549 Cell Line | EDJ-KQ66765 | Human | 130399 | Details Get a Quote |
| ACVR1C Knockout HCT 116 Cell Line | EDJ-KQ75171 | Human | 130399 | Details Get a Quote |
| ACVR1B and TGFBR1 Knockout HEK293 Cell Line | EDC08097 | Human | 91 and 7046 | Details Get a Quote |
| ACVR1B Knockout HAP1 Cell Line | EDC08195 | Human | 91 | Details Get a Quote |
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