Normal Function
The YY1AP1 gene provides instructions for making a protein that is part of a group of proteins known as the INO80 chromatin remodeling complex. In the cell nucleus, this protein complex binds to chromatin, which is the network of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling by the INO80 chromatin remodeling complex allows cells to control the activity (expression) of certain genes.
The INO80 chromatin remodeling complex helps regulate several critical cell functions, including cell maturation (differentiation) and cell growth and division (proliferation). In particular, the INO80 chromatin remodeling complex is necessary for the differentiation of bone cells. Activity of the INO80 chromatin remodeling complex also appears to be particularly important in smooth muscle cells, which line the walls of blood vessels.
Health Conditions Related to Genetic Changes
Grange syndrome
Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the YY1AP1 gene cause Grange syndrome. Grange syndrome is a rare condition that causes narrowing (stenosis) and blockage (occlusion) of the blood vessels that supply blood to many organs and tissues, including the kidneys, brain, and heart. People with Grange syndrome can also have short fingers and toes (brachydactyly), fused fingers or toes (syndactyly), bones that are prone to breakage, learning disabilities, and heart defects.
Pathogenic variants in the YY1AP1 gene are described as "loss-of-function variants" because they reduce or eliminate the activity of the YY1AP1 protein. Without functioning YY1AP1 proteins, the INO80 chromatin remodeling complex cannot effectively control gene expression. This likely impairs the differentiation of smooth muscle cells. As a result, blood vessel walls do not develop normally, leading to stenosis and occlusion. Similarly, the loss of functional INO80 chromatin remodeling complex impairs the differentiation of bone cells and reduces the accumulation of calcium and other minerals (mineralization) in bones. This likely contributes to the bone abnormalities seen in people with Grange syndrome.
More About This Health ConditionOther Names for This Gene
- HCCA2
- YAP
- YY1AP
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Akalin A, Oz V, Pinarbasi AS, Ozalkak S, Karaca MS, Yildirim R. A Novel YY1AP1 Variant in Grange Syndrome: Clinical and Molecular Findings in Eight Individuals With a Dual Molecular Diagnosis Involving CLMP in One Patient. Am J Med Genet A. 2026 Sep;200(9):2036-2051. doi: 10.1002/ajmg.a.70170. Epub 2026 Apr 17. Citation on PubMed
- Guo DC, Duan XY, Regalado ES, Mellor-Crummey L, Kwartler CS, Kim D, Lieberman K, de Vries BBA, Pfundt R, Schinzel A, Kotzot D, Shen X, Yang ML; University of Washington Center for Mendelian Genomics; Bamshad MJ, Nickerson DA, Gornik HL, Ganesh SK, Braverman AC, Grange DK, Milewicz DM. Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease. Am J Hum Genet. 2017 Jan 5;100(1):21-30. doi: 10.1016/j.ajhg.2016.11.008. Epub 2016 Dec 8. Citation on PubMed or Free article on PubMed Central
- Morrison AJ, Shen X. Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nat Rev Mol Cell Biol. 2009 Jun;10(6):373-84. doi: 10.1038/nrm2693. Epub 2009 May 8. Citation on PubMed
- Unsel-Bolat G, Tezcan N, Genc-Akdag D, Gerik-Celebi HB, Tezcan A, Bolat H. A novel compound heterozygous YY1AP1 variant in Grange syndrome: importance of early signs in preventing life-threatening vascular complications. J Hum Genet. 2026 Aug;71(8):485-492. doi: 10.1038/s10038-026-01471-0. Epub 2026 Mar 26. Citation on PubMed
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