Adolescent idiopathic scoliosis (AIS) is a type of scoliosis characterized not only by the curvature of the spine but also by the age at which it develops. AIS occurs in individuals between the ages of 10 and 18 years old and is defined as a lateral curvature of the spine with an angle exceeding 10 degrees. “Idiopathic” refers to scoliosis without a specific cause; however, the Scoliosis Research Society (2025) found that 30% of AIS patients have family members who have had scoliosis. Having AIS can lead to several physical symptoms, including a back or rib hump, uneven shoulders, and a torso lean due to the curvature of the spine. These symptoms can result in discomfort and even back pain, particularly in the lower back. Rebello et al. (2023) found the gene COL11A2 played a key role in vertebral development. While some COL11A2 variants have been classified, 96% of them have not. Classifying these variants can help to diagnose AIS at earlier stages and prevent further spinal curvature. Clinical submissions reported in the Ensembl database categorized pathogenic, benign and unclassified variants. YASARA modeling of the COL11A2 protein was used to examine the structural characteristics relative to regions with unclassified variants. SIFT, PolyPhen, Revel, CADD and MetaLR scores were normalized and plotted to compare known pathogenic and benign variants with selected R130W and R130Q unclassified variants. Molecular dynamics simulations were performed to model 20 nanoseconds of movement in an aqueous environment for the wild type COL11A2 as well as the two variants, R130W and R130Q. The results of these methods are mixed. The analysis of the in-silico predictor scores, as well as the chemical difference between arginine and tryptophan suggested that R130W may be pathogenic. Swaps between glutamine and arginine appear in 44.8% of pathogenic missense mutations in COL11A2. However, gene conservation analysis yielded low scores for position 130 when over 150 homologues and the molecular dynamics simulations for both R130W and R130Q demonstrated little divergence from the wild type COL11A2. This research will aid future studies into these mutations and other mutations of this gene, which will help to discover any existing links to adolescent idiopathic scoliosis and ultimately improve the ability of physicians to diagnose this condition before it becomes more severe.

References: Denise Rebello, Elizabeth Wohler, Vida Erfani, Guozhuang Li, Alexya N Aguilera, Alberto Santiago-Cornier, Sen Zhao, Steven W Hwang, Robert D Steiner, Terry Jianguo Zhang, Christina A Gurnett, Cathleen Raggio, Nan Wu, Nara Sobreira, Philip F Giampietro, Brian Ciruna, COL11A2 as a candidate gene for vertebral malformations and congenital scoliosis, Human Molecular Genetics, Volume 32, Issue 19, 1 October 2023, Pages 2913–2928, https://doi.org/10.1093/hmg/ddad117 Scoliosis Research Society. (2025). Adolescent Idiopathic Scoliosis. Scoliosis Research Society, Springer Nature, www.srs.org/Patients/Conditions/Scoliosis/Idiopathic-Scoliosis.