Rho GTPase activity and cytoskeletal organization44–46. Other credible causal genes in the locus include CLP1 (cleavage factor polyribonucleotide kinase subunit 1), TMX2 (thioredoxin-related transmembrane protein 2) and ZDHHC5 (zinc finger DHHC type palmitoyltransferase 5). Rare genetic mutations in CLP1 are associated with pontocerebellar hypoplasia type 10, a very rare autosomal recessive neurodegenerative disease characterized by brain atrophy and delayed myelination resulting in intellectual disability47. TMX2 is associated with increased risk of neurodevelopmental disorders with microcephaly, cortical malformations, spasticity and congenital nervous system abnormalities48. ZDHHC5 is broadly expressed in the brain, including the frontal cortex. ZDHHC5 has not been implicated in brain development but has been linked to lung acinar adenocarcinoma and lung papillary adenocarcinoma in prior studies49.
