Fig. 1

Study workflow. Candidate NDD HNRNPs were determined from the literature and publicly available information (such as amino acid sequences) and from identification of probands in our novel cohorts. The candidate NDD HNRNPs were finalized by considering only genes in which at least three probands were identified from published and/or novel sources. Functional impacts focused on these finalized NDD HNRNP candidates and included pathogenicity predictions (gnomAD and GEVIR), de novo enrichment analyses (using the Chimpanzee–Human [CH] model and denovolyzeR), missense analyses (using CLUMP and MetaDome), expression analyses of fetal cortex and adult tissues, and phenotypic analyses within HNRNPs, across HNRNPs, and in comparison to other similarly presenting disorders by HPO terms. CNV: copy number variant; pLI: loss-of-function intolerance; LGD: likely gene disrupting; NMD: nonsense mediated decay; HPO: human phenotype ontology