Submission Details

Autosomal recessive

09/17/2020

The FKBP10 gene is located on chromosome 17 at 17q21.2 and encodes the FKBP prolyl isomerase 10 protein, which is a member of the immunophilins group of proteins. FKBP prolyl isomerase 10 protein has peptidyl prolyl cis-trans isomerase activity (PPIase) that accelerates protein folding, and it may also enable collagen folding by acting as a collagen chaperon. FKBP10 was first reported in relation to autosomal recessive osteogenesis imperfecta with or without joint contractures in 2010 (20362275: Alanay et al. (2010). At least six unique loss-of-function variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least six probands from four publications (20362275: Alanay et al. 2010; 21567934: Shaheen et al. 2011; 20839288: Kelley et al. 2011; 27762305: Xu et al. 2017). Segregation was noted in four families but with insufficient evidence to score. More genetic evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is supported by expression studies and animal models. In summary, FKBP10 is definitively associated with autosomal recessive osteogenesis imperfecta with or without joint contractures. Lumping and Splitting: Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism(s) underlying the disease entities (Marini et al. 2014): Bruck syndrome 1 (MIM:259450) and Osteogenesis imperfecta, type XI (MIM:610968).

20362275 21567934 20839288 27762305 24777781