Alternative titles; symbols
HGNC Approved Gene Symbol: ACVR2B
Cytogenetic location: 3p22.2 Genomic coordinates (GRCh38): 3:38,453,890-38,493,142 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3p22.2 | Heterotaxy, visceral, 4, autosomal | 613751 | 3 |
Activins are gonadal polypeptide hormones that are potent stimulators of FSH secretion and release in vitro (see 147380). Activins are dimers of 2 beta subunits that share extensive sequence homology with transforming growth factor-beta (190180). There are 2 classes of activin receptors, type I and type II (see ACVR2; 102581). By RT-PCR with primers based on the sequences of rodent type II activin receptor genes, Hilden et al. (1994) cloned an ACVR2B cDNA from the K562 erythroleukemic cell line. The predicted 512-amino acid protein, which they called ActRIIB, was 99% identical to the mouse homolog and 69% identical to ACVR2. ACVR2B contains an extracellular ligand binding domain, a transmembrane domain, and an intracellular serine/threonine kinase domain. Northern blot analysis of fetal tissues revealed that ACVR2B mRNAs are variably expressed in several tissues, with the highest level of expression in brain. On Northern blots of K562 cell mRNA, Hilden et al. (1994) found that ACVR2B was expressed predominantly as 2.5- and 10-kb transcripts, with a very weak signal at 2.1 kb.
Lee et al. (2005) showed that ligands such as myostatin (MSTN; 601788) signal through mouse Acvr2 and Acvr2b to regulate muscle growth in vivo.
Ishikawa et al. (1998) reported that the ACVR2B gene contains 11 exons and spans approximately 30 kb.
Kosaki et al. (1999) reported the intron-exon organization of the human ACVR2B gene and compared their findings with those of Ishikawa et al. (1998).
By its inclusion within a contig and fluorescence in situ hybridization, Ishikawa et al. (1998) mapped the ACVR2B gene to 3p22-p21.3. By FISH, Bondestam et al. (1999) mapped the ACVR2B gene to 3p22.
In patients with left-right axis malformations (613751), Kosaki et al. (1999) identified heterozygous mutations in the ACVR2B gene (602730.0001-602730.0002).
Burdine and Schier (2000) reviewed convergent and divergent mechanisms in left-right axis formation in chick, mouse, frog, and zebrafish and the role of mutations in EBAF (601877), ACVR2B, ZIC3 (300265), and connexin-43 (121014) in humans.
Oh and Li (1997) found that targeted disruption of the mouse Acvr2b gene results in abnormal left-right (LR) axis development in Acvr2b -/- homozygotes. Resulting malformations include atrial and ventricular septal defects, right-sided morphology of the left atrium and left lung, and spleen hypoplasia.
Lin et al. (1999) generated homozygous knockout mice for the Pitx2 (601542) gene by targeted disruption. The cardiac and pulmonary phenotype of these mice was indistinguishable from those of Acvr2b knockout mice, indicating that Pitx2 is the critical downstream target of Acvr2b, a putative Nodal (601265) receptor.
In 2 unrelated patients with left-right axis malformations (613751), Kosaki et al. (1999) found a G-to-A transition at nucleotide 119 in exon 2 of the ACVR2B gene resulting in an arg40-to-his amino acid substitution. One of the patients had ventricular inversion (dextrocardia), but intact ventricular septum and normally related great arteries. The patient also had a right aortic arch and a right-sided spleen, as well as anomalies of the inferior and the superior vena cava. The second patient had a complete atrial ventricular canal defect with dextro-transposed great arteries and obstruction to pulmonary outflow. Pulmonary venous return was normal, but like the first patient, there was an interrupted inferior vena cava with azygous continuation. This patient also had polysplenia and midline liver. The mutation was not found in 100 randomly selected control individuals.
In a patient with left-right axis malformations (613751), Kosaki et al. (1999) found a G-to-A transition at nucleotide 1480 in exon 11 of the ACVR2B gene resulting in a val494-to-ile amino acid substitution of the protein product. The patient had ventricular inversion with ventricular septal defect, inversion and transposition of the great vessels, pulmonary stenosis, total anomalous pulmonary venous return, and midline liver. The mutation was not found in 100 randomly selected control individuals.
Bondestam, J., Horelli-Kuitunen, N., Hilden, K., Ritvos, O., Aaltonen, J. Assignment of ACVR2 and ACVR2B the human activin receptor type II and IIB genes to chromosome bands 2q22.2-q23.3 and 3p22 and the human follistatin gene (FST) to chromosome 5q11.2 by FISH. Cytogenet. Cell Genet. 87: 219-220, 1999. [PubMed: 10702675] [Full Text: https://doi.org/10.1159/000015429]
Burdine, R. D., Schier, A. F. Conserved and divergent mechanisms in left-right axis formation. Genes Dev. 14: 763-776, 2000. [PubMed: 10766733]
Hilden, K., Tuuri, T., Eramaa, M., Ritvos, O. Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor. Blood 83: 2163-2170, 1994. [PubMed: 8161782]
Ishikawa, S., Kai, M., Murata, Y., Tamari, M., Daigo, Y., Murano, T., Ogawa, M., Nakamura, Y. Genomic organization and mapping of the human activin receptor type IIB (hActR-IIB) gene. J. Hum. Genet. 43: 132-134, 1998. [PubMed: 9621519] [Full Text: https://doi.org/10.1007/s100380050054]
Kosaki, R., Gebbia, M., Kosaki, K., Lewin, M., Bowers, P., Towbin, J. A., Casey, B. Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB. Am. J. Med. Genet. 82: 70-76, 1999. [PubMed: 9916847] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19990101)82:1<70::aid-ajmg14>3.0.co;2-y]
Lee, S.-J., Reed, L. A., Davies, M. V., Girgenrath, S., Goad, M. E. P., Tomkinson, K. N., Wright, J. F., Barker, C., Ehrmantraut, G., Holmstrom, J., Trowell, B., Gertz, B., Jiang, M.-S., Sebald, S. M., Matzuk, M., Li, E., Liang, L., Quattlebaum, E., Stotish, R. L., Wolfman, N. M. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc. Nat. Acad. Sci. 102: 18117-18122, 2005. [PubMed: 16330774] [Full Text: https://doi.org/10.1073/pnas.0505996102]
Lin, C. R., Kioussi, C., O'Connell, S., Briata, P., Szeto, D., Liu, F., Izpisua-Belmonte, J. C., Rosenfeld, M. G. Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature 401: 279-282, 1999. [PubMed: 10499586] [Full Text: https://doi.org/10.1038/45803]
Oh, S. P., Li, E. The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse. Genes Dev. 11: 1812-1826, 1997. [PubMed: 9242489] [Full Text: https://doi.org/10.1101/gad.11.14.1812]