Two de novo variants (one nonsense, one missense) in the NUAK1 gene were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2012 and Iossifov et al., 2014. Krumm et al., 2015 reported that no de novo SNVs in this gene were observed in SSC unaffected siblings (de novo SNV P-value <0.05), and no rare effect types were reported in the Exome Variant Server.
Molecular Function
This gene encodes a serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo gene disruptions in children on the autistic spectrum.
Loss of one allele of Nuak1 in neurons of mice leads to abnormal cortical development and connectivity, deficits in spatial memory consolidation, abnormal sensorimotor gating, deficits in social memory but no change in social approach. Reinstatement of Nuak1 expression in neurons rescues deficits in axonal phenotypes.
References
Type
Title
Author, Year
Primary
Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A lacZ cassette with a neo cassette was inserted just upstream of the translation initiation site followed by a PolyA transcription termination sequence (pA) leading to a consitutive null mutation. Long-term in utero cortical electroporation was performed to label the axons of layer 2/3 pyramidal neurons in the primary somatosensory cortex.
Allele Type: Knockout
Strain of Origin: Genetic Background: C57Bl/6 J
ES Cell Line: Mutant ES Cell Line: Model Source: Riken institute
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A lacZ cassette with a neo cassette was inserted just upstream of the translation initiation site followed by a PolyA transcription termination sequence (pA) leading to a consitutive null mutation. Long-term in utero cortical electroporation was performed to label the axons of layer 2/3 pyramidal neurons in the primary somatosensory cortex.
Allele Type: Knockout
Strain of Origin: Genetic Background: C57Bl/6 J
ES Cell Line: Mutant ES Cell Line: Model Source: Riken institute
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Mosaic homozygous deletion of exon 2 of the Nuak1 gene by in utero, cortical, electroporation of CAG-cre at E15.5, in widespread cells and tissues of the offspring
Allele Type: Mosaic
Strain of Origin: Genetic Background: C57Bl/6 J
ES Cell Line: Mutant ES Cell Line: Model Source: KOMP Repository from UC Davis
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mosaic heterozygous deletion of exon 2 of the Nuak1 gene by in utero, cortical, electroporation of CAG-cre at E15.5, in widespread cells and tissues of the offspring
Allele Type: Mosaic
Strain of Origin: Genetic Background: C57Bl/6 J
ES Cell Line: Mutant ES Cell Line: Model Source: KOMP Repository from UC Davis
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Conditional heterozygous deletion of exon 2 of the Nuak1 gene using Nex-cre, in the neurons of the dorsal telencephalon, authors note that NEX-cre is expressed expression in intermediate progenitors and in PNs of the dorsal telencephalon, excluding GABAergic interneurons and astrocytes or other non-neuronal cells.
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: C57Bl/6 J
ES Cell Line: Mutant ES Cell Line: Model Source: KOMP Repository from UC Davis
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 2 of the Nuak1 gene using Nex-cre, in the neurons of the dorsal telencephalon, authors note that Nex-cre is expressed in intermediate progenitors and in pyramidal neurons of the dorsal telencephalon, excluding GABAergic interneurons and astrocytes or other non-neuronal cells.
Allele Type: Conditional loss-of-function
Strain of Origin: null
Genetic Background: null
ES Cell Line: null
Mutant ES Cell Line: null
Model Source: null
Description: Het mutants show decrease in body weight and size at p26 and p40 but not at p18, compared with controls, more pronounced in males than females.
Exp Paradigm: NA
Description: Het mutants show no change in preference for the target quadrant during the probe trial compared with controls, immediately following training. however het mutants show decrease in time spent in the target quadrant one month after training compared with controls.
Exp Paradigm: NA
Description: Mutants with conditional cortical null deletion of nuak1 show decrease in terminal axon branching on the contralateral hemisphere layer ii/iii neurons compared with controls, indicating a role for nuak1 in cortico-cortical connectivity during postnatal development.
Exp Paradigm: NA
Description: Het mutants with conditional cortical deletion of nuak1 show decrease in terminal axon branching on the contralateral hemisphere layer ii/iii neurons compared with controls, indicating a role for nuak1 in cortico-cortical connectivity during postnatal development.
Exp Paradigm: NA
Description: Het mutants with conditional deletion of nuak1 in the telencephalon displayed no preference for the novel mouse compared with controls.
Exp Paradigm: NA
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Het mutants with conditional deletion of nuak1 in the telencephalon show decrease in response to memory of the cue of the fear conditioning test compared with controls.
Exp Paradigm: NA
Description: Mutants with conditional deletion of nuak1 in the telencephalon displayed no preference for the novel mouse compared with controls.
Exp Paradigm: NA
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Mutants with conditional deletion of nuak1 in the telencephalon show decrease in response to memory of the cue of the fear conditioning test compared with controls.
Exp Paradigm: NA
