Aliases: DDX9, LKP, NDH2, NDHII, RHA
Chromosome No: 1
Chromosome Band: 1q25.3
Genetic Category: Rare single gene variant-Rare single gene variant/Functional-Syndromic/Functional
ASD Reports: 5
Recent Reports: 1
Annotated variants: 25
Associated CNVs: 6
Evidence score: 3
| Associated Disorders: |
|
Relevance to Autism
Yamada et al., 2023 demonstrated that two de novo missense variants in the DHX9 gene (a p.Arg1052Gln variant that was previously reported in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and a p.Gly414Arg variant that was identified in a novel patient presenting with developmental delay/intellectual disability, undergrowth, and ventricular non-compaction cardiomyopathy) resulted in aberrant localization and loss-of-function effects in transgenic Drosophila lines. In the same report, the authors also found that mice heterozygous for a p.Gly416Arg variant, which corresponded to the p.Gly414Arg variant, displayed reduced body weight, reduced emotionality, and cardiac conduction abnormalities (prolonged PR interval). Additional de novo variants in the DHX9 gene, including a de novo loss-of-function variant, have been identified in ASD probands from simplex families from the MSSNG cohort (Zhou et al., 2022), while a paternally-inherited DHX9 missense variant with a CADD score of 31 was identified in a Chinese ASD proband from the ACGC cohort (Guo et al., 2018). Calame et al., 2023 described 20 individuals with rare monoallelic DHX9 variants presenting with either a neurodevelopmental disorder characterized by developmental delay/intellectual disability, neuropsychiatric disorders (including autism spectrum disorder), seizures, axial hypotonia, and dysmorphic features, or Charcot-Marie-Tooth disease; subsequent functional studies demonstrated that DHX9 variants disrupted cellular localization and helicase activity and increased R-loops and double-stranded DNA breaks, while a Dhx9 -/- mice was shown to exhibit behavioral and neurological abnormalities in this report.
Molecular Function
This gene encodes a member of the DEAH-containing family of RNA helicases. The encoded protein is an enzyme that catalyzes the ATP-dependent unwinding of double-stranded RNA and DNA-RNA complexes. This protein localizes to both the nucleus and the cytoplasm and functions as a transcriptional regulator. This protein may also be involved in the expression and nuclear export of retroviral RNAs. Alternate splicing results in multiple transcript variants.
External Links
