CDK16

Inheritance Pattern: XL

Disease ID:MONDO:0100148

Submitter: ClinGen

*CDK16* was first reported in relation to X-linked intellectual disability and spastic paraplegia in 2016 (Hu et al., PMID: 25644381). Within this publication, the variant segregated with disease in three additional family members. Since then, only one additional human case has been reported, this time in association with West syndrome (Peng et al., 2018, PMID: 29667327). Within these publications, two unique variants, one frameshift (predicted null) and one missense, have been reported. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, disease entities were lumped. Although two phenotypes were identified via publication, including intellectual disability with spastic paraplegia and West syndrome, no distinct differences in molecular mechanism or inheritance pattern were identified. Therefore, all of the disease entities have been lumped into one disease entity, complex neurodevelopmental disorder. Evidence supporting this gene-disease relationship includes case level data and experimental data. For the purposes of this curation, two variants in this gene were scored in the two publications mentioned above (PMIDs: 25644381, 29667327). This gene-disease association is also supported by data from protein expression analysis, two hybrid screens, targeted mutagenesis, and in vitro chemical genetic screens (PMIDs: 100099831, 20510931, 26205494, 16461345 and 30880224). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts this gene-disease relationship. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on October 28, 2021 (SOP Version 8).

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: G2P