ACVR1B (Activin A Receptor Type 1B)
A serine/threonine kinase receptor in the TGF-beta signaling pathway, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | ACVR1B |
|---|---|
| Full Name | Activin A receptor type 1B |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 91 ncbi.nlm.nih.gov/gene/91 |
| Ensembl ID | ENSG00000135503 |
| UniProt ID | P36896 |
| OMIM ID | 601300 |
| HGNC ID | 172 |
| Aliases | ALK4, ACTRIB, ACVRLK4, SKR2 |
Description
ACVR1B (Activin A receptor type 1B) encodes a serine/threonine kinase receptor that binds activin and other TGF-beta family ligands. Upon ligand binding, it phosphorylates SMAD2/SMAD3, regulating transcription of genes involved in cell proliferation, differentiation, and apoptosis. Mutations and altered expression of ACVR1B are associated with various cancers, including pancreatic and colorectal cancer, as well as developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic cancer | Somatic mutations (e.g., missense) in ACVR1B disrupt TGF-beta signaling, promoting tumor growth. | COSMIC; PMID: 22956686 |
| Colorectal cancer | Loss-of-function mutations impair growth inhibition, contributing to tumor progression. | COSMIC; PMID: 16959974 |
| Pituitary adenoma | ACVR1B overexpression or mutation alters activin signaling, affecting hormone secretion. | PMID: 15634788 |
| Fibrodysplasia ossificans progressiva (FOP) | Rare ACVR1B variants may modify BMP/activin signaling, but ACVR1 (ALK2) is primary. | ClinVar; PMID: 16912704 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 5.4 | Medium |
| Brain | 3.2 | Low |
| Colon | 6.1 | Medium |
| Heart | 2.8 | Low |
| Kidney | 4.5 | Medium |
| Liver | 3.9 | Low |
| Lung | 5.0 | Medium |
| Pancreas | 7.2 | Medium |
| Placenta | 8.5 | High |
| Testis | 6.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 6.3 | Cervical cancer cell line |
| A549 | 5.1 | Lung cancer cell line |
| HEK 293 | 7.0 | Embryonic kidney cell line |
| MCF7 | 4.8 | Breast cancer cell line |
| HepG2 | 5.5 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1157G>A (p.Arg386His) | Missense | <1% | Loss of kinase activity; associated with colorectal cancer (COSMIC COSM37580) |
| c.1460G>A (p.Arg487Gln) | Missense | <1% | Impaired SMAD2 phosphorylation; reported in pancreatic cancer (COSMIC COSM37581) |
| c.1099C>T (p.Arg367*) | Nonsense | <1% | Truncated protein; loss of function (ClinVar) |
| c.1244A>G (p.Asn415Ser) | Missense | <1% | Reduced ligand binding; somatic in pituitary adenoma (COSMIC COSM37582) |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations that reduce or abolish kinase activity or SMAD phosphorylation, leading to disrupted TGF-beta signaling and tumor progression.
Gain of Function (GOF)
Not well-documented; most reported mutations are loss-of-function.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg386His) may act dominant-negative by forming inactive receptor complexes.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0004675 (transmembrane receptor protein serine/threonine kinase activity) |
| • GO:0005024 (transforming growth factor beta receptor activity | • type I) |
| • GO:0007179 (transforming growth factor beta receptor signaling pathway) | • GO:0016301 (kinase activity) |
| • GO:0016740 (transferase activity) | • GO:0046332 (SMAD binding) |
| • GO:0046872 (metal ion binding) |
Pathways
• TGF-beta signaling pathway (KEGG: hsa04350)
• Activin receptor signaling (Reactome: R-HSA-2473224)
• Signaling by TGF-beta family members (Reactome: R-HSA-9006936)
• SMAD2/SMAD3 phosphorylation (Reactome: R-HSA-2173793)
Protein Summary
ACVR1B (ALK4) is a 505-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 activin binding, it forms a complex with type II receptors (e.g., ACVR2A) and phosphorylates SMAD2/SMAD3, which then translocate to the nucleus to regulate gene expression. The protein is widely expressed and plays a critical role in development, cell cycle control, and tumor suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACVR1B Knockout HEK293 Cell Line | EDJ-KQ362 | Human | 91 | Details Get a Quote |
| ACVR1B Knockout A-549 Cell Line | EDJ-KQ17978 | Human | 91 | 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 |
| ACVR1B & TGFBR1 Knockout HEK293 Cell Line | EDC08097 | Human | 91 & 7046 | Details Get a Quote |
| ACVR1B Knockout HAP1 Cell Line | EDC08195 | Human | 91 | Details Get a Quote |
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