Two de novo loss-of-function (LoF) variants were identified in ASD probands in Yuen et al., 2017 (one in a proband from a simplex family, the other in a proband from a multiplex family). Based on the discovery of two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), KDM6A was determined to be an ASD candidate gene in Yuen et al., 2017.
Molecular Function
This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Mutations in the KDM6A gene are associated with Kabuki syndrome 2 (KABUK2; OMIM 300867), a congenital intellectual disability syndrome with additional features including postnatal dwarfism and distinct facial dysmorphic features.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing
Model Type:
Genetic
Model Genotype:
Wildtype
Mutation:
Knockdown was performed by injecting a 2ng dose (1nl) of translation-blocking kdm6a morpholino into one-cell stage embryos.
Allele Type: Knockdown
Strain of Origin: Unreported
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: Unreported
Model Type:
Genetic
Model Genotype:
Wildtype
Mutation:
Double morpholino knockdown was performed by injecting a 1ng dose (1nl) of translation-blocking kdm6a morpholino and 1ng dose (1nl) of translation-blocking kdm6a-like morpholino into one-cell stage embryos.
Allele Type: Knockdown
Strain of Origin: Unreported
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: Unreported
Description: Kdm6a morphants showed a decrease in the size of the lower jaw, hypoplastic Meckels cartilage, palatoquadrates, ceratohyals, and ceratobranchials compared to controls. Moreover, the in kdm6a morphants, the ethmoid plate failed to extend along its axis.
