ACVR2B

Chr 3

activin A receptor type 2B

Also known as: ACTRIIB, ActR-IIB, HTX4

NCBI Gene: 93ENSG00000114739UniProt: Q13705OMIM: 602730

The ACVR2B protein is a transmembrane serine/threonine kinase that serves as the primary receptor for activin signaling, binding activin ligands and phosphorylating downstream type-1 receptors to regulate processes including neuronal differentiation, wound healing, and follicular development. Mutations cause autosomal dominant heterotaxy with visceral malformations involving abnormal left-right body axis patterning. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismLOEUF 0.381 OMIM phenotype
Clinical Summary— ACVR2B
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 227 VUS of 405 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.834
Z-score 4.02
OE 0.18 (0.09–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.04Z-score
OE missense 0.67 (0.59–0.75)
196 obs / 294.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.18 (0.09–0.38)
0≤0.351.4
Missense OE0.67 (0.59–0.75)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 5 / 27.9Missense obs/exp: 196 / 294.7Syn Z: -1.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedACVR2B-related heterotaxy syndromeOTHERAD
DN
0.5378th %ile
GOF
0.6639th %ile
LOF
0.55top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

405 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS227
Likely Benign69
Benign85
Conflicting3
10
Pathogenic
3
Likely Pathogenic
227
VUS
69
Likely Benign
85
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
2
1
0
3
VUS
4
75
143
5
227
Likely Benign
0
4
30
35
69
Benign
0
0
80
5
85
Conflicting
—3
Total48126445397

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ACVR2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Genetic polymorphisms of muscular fitness in young healthy men
Venckunas T et al.·PLoS One
2022
The association between sarcopenia susceptibility and polymorphisms of FTO, ACVR2B, and IRS1 in Tibetans
Zhang X et al.·Mol Genet Genomic Med
2021
Activin A and Acvr2b mRNA from Umbilical Cord Blood Are Not Reliable Markers of Mild or Moderate Neonatal Hypoxic-Ischemic Encephalopathy.
O'Sullivan MP et al.·Neuropediatrics
2021
Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2/Acvr2b competitive receptor-activated Smad pathway.
Liu A et al.·Biomaterials
2021
Establishment and verification of a prognostic risk score model based on immune genes for hepatocellular carcinoma in an Asian population
Wang Y et al.·Transl Cancer Res
2023Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients