ACVR1B

Chr 12

activin A receptor type 1B

Also known as: ACTRIB, ACVRLK4, ALK4, SKR2

NCBI Gene: 91ENSG00000135503UniProt: P36896OMIM: 601300

This gene encodes a transmembrane serine/threonine kinase that functions as an activin type I receptor, transducing activin signals through SMAD-mediated pathways to regulate neuronal differentiation and survival, along with multiple other developmental processes. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.17), but currently has only somatic cancer associations in OMIM rather than established germline developmental disorders. Activin signaling is critical for nervous system development, suggesting potential for neurodevelopmental phenotypes from germline mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanism1 OMIM phenotype
Clinical Summary— ACVR1B
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 41 VUS of 61 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

DN
0.3694th %ile
GOF
0.5857th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 20% of P/LP variants are LoF

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS41
Benign2
9
Pathogenic
1
Likely Pathogenic
41
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
6
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
38
3
0
41
Likely Benign
0
0
0
0
0
Benign
0
0
1
1
2
Total23911153

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

View in ClinVar →

Protein Context — Lollipop Plot

ACVR1B · 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
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution.
Boueiz A et al.·Am J Respir Cell Mol Biol
2019
Acvr1b Loss Increases Formation of Pancreatic Precancerous Lesions From Acinar and Ductal Cells of Origin.
Saeki K et al.·Cell Mol Gastroenterol Hepatol
2024
Implication of rare genetic variants of NODAL and ACVR1B in congenital heart disease patients from Indian population.
Yadav ML et al.·Exp Cell Res
2021Cohort
Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage-tumor interaction axes among different lineages of pituitary neuroendocrine tumors.
Lin S et al.·Genome Med
2024
Bioinformatics Analysis of the Genetic and Epigenetic Alterations of Bone Morphogenetic Protein Receptors in Metastatic Breast Cancer.
Hermawan A et al.·Biochem Genet
2024Review
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