ACVR2A
protein-codingactivin A receptor type 2A, the group of Type 2 receptor serine/threonine kinases
Gene summary
This gene encodes a receptor that mediates the functions of activins, which are members of the transforming growth factor-beta (TGF-beta) superfamily involved in diverse biological processes. The encoded protein is a transmembrane serine-threonine kinase receptor which mediates signaling by forming heterodimeric complexes with various combinations of type I and type II receptors and ligands in a cell-specific manner. The encoded type II receptor is primarily involved in ligand-binding and includes an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic serine-threonine kinase domain. This gene may be associated with susceptibility to preeclampsia, a pregnancy-related disease which can result in maternal and fetal morbidity and mortality. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jun 2013]
- ACVR2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ACVR2A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001616.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 33 | 33 | ||||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 42 | 0 | 0 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001607.1 | 11 | MANE Select | |
| Ensembl | ENSP00000241416.7 | 11 | MANE Select | |
| RefSeq | NP_001265508.1 | 11 | Standard | |
| RefSeq | NP_001265509.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| acvr2aa | Danio rerio | Structure: endochondral bone Quality: aplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-beta signaling pathway - Homo sapiens (human)
- Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- Mesodermal Commitment Pathway
Biological Process
- gastrulation with mouth forming second
- positive regulation of protein phosphorylation
- protein phosphorylation
- transmembrane receptor protein serine/threonine kinase signaling pathway
- transforming growth factor beta receptor signaling pathway
Molecular Function
- protein serine/threonine kinase activity
- transmembrane receptor protein serine/threonine kinase activity
- transforming growth factor beta-activated receptor activity
- transforming growth factor beta receptor activity, type II
- protein binding
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- cell surface
- inhibin-betaglycan-ActRII complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000241416
- Coding exons
- 11
- Length
- 86308
- Individuals with no LoFs
- 125598
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125600
- p
- 0.00000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.29 | 123 | 277 | 0.444 | 0.0000133 | 3379 |
| Missense (PolyPhen) | 23 | 123.76 | 0.18584 | 1558 | ||
| Synonymous | -0.167 | 98 | 95.9 | 1.02 | 0.00000483 | 947 |
| Loss of Function | 4.71 | 1 | 27.8 | 0.0359 | 0.00000137 | 345 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6 (By similarity). {ECO:0000250|UniProtKB:P27038, ECO:0000269|PubMed:1314589}.;
Recessive Scores
- pRec
- 0.240
Intolerance Scores
- LoFtool
- 0.0781
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |