CUL3

• Haploinsufficiency score: 2
• Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: Disease Ontology: 0060041

Evidence for haploinsufficiency phenotype

PubMed ID	Description
22495309	O'Roak et al (2012) found a de novo nonsense change in CUL3 by whole exome sequencing in a patient with autism. No additional clinical information was provided and no additional de novo variants were listed in this individual. The change was in exon 6 of the 16 CUL3 exons.
22914163	Kong et al (2012) report a de novo nonsense variant in exon 12 of the CUL3 gene in a patient with an autism spectrum disorder. Variants were detected by whole genome sequencing. No additional clinical information was provided.
27824329	Wang et al (2016) sequenced 189 genes that they defined as autism risk genes in a cohort of probands with autism spectrum disorders. They found a de novo G>T change at the first position of the donor site in intron 8 of the CUL3 gene. RNA studies were not performed.

Haploinsufficiency phenotype comments:

PMID 22266938: Boyden et al (2012) found that variants, including cannoncial splice variants clustering at the intron 8 splice acceptor and the intron 9 splice donor, in CUL3 cause Pseudohypoaldosteronism type IIE. However, all these mutations result in an in-frame deletion of exon 9. PMID 23665959: Zaidi et al (2013) identified a de novo frameshift variant in exon 4 of CUL3 in a patient with congenital heart disease. The neurodevelopmental profile of the patient is unknown. Variants were detected by whole exome sequencing. PMID 25363760: De Rubeis et al (2014) identified a nonsense variant and a splice variant (inheritance unknown for both) in a cohort of patients with autism.

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity