Reviewed August 2007
What is the official name of the ACVR1 gene?
The official name of this gene is “activin A receptor, type I.”
ACVR1 is the gene's official symbol. The ACVR1 gene is also known by other names, listed below.
What is the normal function of the ACVR1 gene?
The ACVR1 gene provides instructions for making the activin receptor type I protein, which is a member of a protein family called bone morphogenetic protein (BMP) type I receptors. BMP receptors span the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This arrangement allows receptors to receive signals from outside the cell and transmit them inside to affect cell development and function.
Activin receptor type I is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification). This process occurs in normal skeletal maturation from birth to young adulthood.
Activin receptor type I is normally activated at appropriate times by molecules called ligands. Activation may occur when these ligands, such as BMPs, attach (bind) to the receptor or to other proteins with which it forms a complex. A protein called FKBP12 can inhibit activin receptor type I by binding to the receptor and preventing inappropriate (leaky) activation in the absence of ligand.
How are changes in the ACVR1 gene related to health conditions?
- fibrodysplasia ossificans progressiva - caused by mutations in the ACVR1 gene
All individuals with a definite diagnosis of fibrodysplasia ossificans progressiva have a mutation in which the protein building block (amino acid) histidine is substituted for the amino acid arginine at position 206 of the ACVR1 protein (written as Arg206His or R206H). Researchers believe that under certain conditions this mutation may change the shape of the receptor. This shape change may disrupt the binding of an inhibitor protein such as FKBP12 or interfere with other mechanisms that control activation. As a result, the receptor may be constantly activated (constitutive activation), even in the absence of ligands. Constitutive activation of the receptor causes overgrowth of bone and cartilage and fusion of joints, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva.
Where is the ACVR1 gene located?
Cytogenetic Location: 2q23-q24
Molecular Location on chromosome 2: base pairs 157,736,445 to 157,875,861
The ACVR1 gene is located on the long (q) arm of chromosome 2 between positions 23 and 24.
More precisely, the ACVR1 gene is located from base pair 157,736,445 to base pair 157,875,861 on chromosome 2.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about ACVR1?
You and your healthcare professional may find the following resources about ACVR1 helpful.
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for ACVR1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=90%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28ACVR1%5BTIAB%5D%29%20OR%20%28%28ALK2%5BTIAB%5D%29%20OR%20%28SKR1%5BTIAB%5D%29%20OR%20%28ACTRI%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/102576)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/ACVR1ID564ch2q24.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=90)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=171)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/90)
What other names do people use for the ACVR1 gene or gene products?
- activin A receptor, type II-like kinase 2
- activin A type I receptor
- activin A type I receptor precursor
- ActR-IA protein, human
- hydroxyalkyl-protein kinase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding ACVR1?
amino acid ;
cell membrane ;
You may find definitions for these and many other terms in the Genetics Home Reference
- OMIM: ACTIVIN A RECEPTOR, TYPE I (http://omim.org/entry/102576)
- Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors. 2004 Dec;22(4):233-41. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15621726?dopt=Abstract)
- de Sousa Lopes SM, Roelen BA, Monteiro RM, Emmens R, Lin HY, Li E, Lawson KA, Mummery CL. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev. 2004 Aug 1;18(15):1838-49. (http://www.ncbi.nlm.nih.gov/pubmed/15289457?dopt=Abstract)
- Fiori JL, Billings PC, de la Peña LS, Kaplan FS, Shore EM. Dysregulation of the BMP-p38 MAPK signaling pathway in cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res. 2006 Jun;21(6):902-9. (http://www.ncbi.nlm.nih.gov/pubmed/16753021?dopt=Abstract)
- Groppe JC, Shore EM, Kaplan FS. Functional modeling of the ACVR1 (R206H) mutation in FOP. Clin Orthop Relat Res. 2007 Sep;462:87-92. (http://www.ncbi.nlm.nih.gov/pubmed/17572636?dopt=Abstract)
- Kaplan FS, Glaser DL, Pignolo RJ, Shore EM. A new era for fibrodysplasia ossificans progressiva: a druggable target for the second skeleton. Expert Opin Biol Ther. 2007 May;7(5):705-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17477807?dopt=Abstract)
- Lin GT, Chang HW, Liu CS, Huang PJ, Wang HC, Cheng YM. De novo 617G-A nucleotide mutation in the ACVR1 gene in a Taiwanese patient with fibrodysplasia ossificans progressiva. J Hum Genet. 2006;51(12):1083-6. Epub 2006 Nov 1. (http://www.ncbi.nlm.nih.gov/pubmed/17077940?dopt=Abstract)
- Nakajima M, Haga N, Takikawa K, Manabe N, Nishimura G, Ikegawa S. The ACVR1 617G>A mutation is also recurrent in three Japanese patients with fibrodysplasia ossificans progressiva. J Hum Genet. 2007;52(5):473-5. Epub 2007 Mar 10. (http://www.ncbi.nlm.nih.gov/pubmed/17351709?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/90)
- O'Connell MP, Billings PC, Fiori JL, Deirmengian G, Roach HI, Shore EM, Kaplan FS. HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells. J Cell Biochem. 2007 Dec 15;102(6):1493-503. (http://www.ncbi.nlm.nih.gov/pubmed/17516498?dopt=Abstract)
- Samad TA, Rebbapragada A, Bell E, Zhang Y, Sidis Y, Jeong SJ, Campagna JA, Perusini S, Fabrizio DA, Schneyer AL, Lin HY, Brivanlou AH, Attisano L, Woolf CJ. DRAGON, a bone morphogenetic protein co-receptor. J Biol Chem. 2005 Apr 8;280(14):14122-9. Epub 2005 Jan 25. (http://www.ncbi.nlm.nih.gov/pubmed/15671031?dopt=Abstract)
- Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7. Epub 2006 Apr 23. Erratum in: Nat Genet. 2007 Feb;39(2):276. FOP International Research Consortium [removed]; Cho, Tae-Joon [added]; Choi, In Ho [added]; Connor, J Michael [added]; Delai, Patricia [added]; Glaser, David L [added]; LeMerrer, Martine [added]; Morhart, Rolf [added]; Rogers, John G [added]; Smith, Roger [added]; Triffitt, James T [added]; Urtizberea, J Andoni [added]; Zasloff, Michael [added]. (http://www.ncbi.nlm.nih.gov/pubmed/16642017?dopt=Abstract)
- Zhang D, Schwarz EM, Rosier RN, Zuscik MJ, Puzas JE, O'Keefe RJ. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J Bone Miner Res. 2003 Sep;18(9):1593-604. (http://www.ncbi.nlm.nih.gov/pubmed/12968668?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.