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Relevance to Autism

Loss of neuronal Uba6 during embryonic development in a mouse model resulted in altered patterning of neurons in the hippocampus and the amygdala, decreased dendritic spine density, and numerous behavioral disorders, including hyperactivity, deficits in social interaction, and increased anxiety (Lee et al., 2013).

Molecular Function

This gene encodes an E1 enzyme that initiates the activation and conjugation of ubiquitin-like proteins.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Altered social behavior and neuronal development in mice lacking the Uba6-Use1 ubiquitin transfer system.
Support
Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.
ASD
Macrocephaly
Support
Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system.
Support
Integrating de novo and inherited variants in 42
ASD
Support
Severe childhood speech disorder: Gene discovery highlights transcriptional dysregulation
Childhood apraxia of speech
DD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN546R001 
 frameshift_variant 
 c.2163_2167del 
 p.Phe722SerfsTer25 
 Familial 
 Paternal 
 Simplex 
 GEN546R002 
 missense_variant 
 c.1766T>C 
 p.Leu589Ser 
 Unknown 
  
  
 GEN546R003 
 synonymous_variant 
 c.2163T>C 
 p.Cys721%3D 
 De novo 
  
  
 GEN546R004 
 missense_variant 
 c.2102A>C 
 p.Glu701Ala 
 De novo 
  
 Multiplex 
 GEN546R005 
 frameshift_variant 
 c.2780_2784del 
 p.Asn927SerfsTer12 
 De novo 
  
  
 GEN546R006 
 splice_site_variant 
 c.1248+1G>A 
  
 De novo 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
4
Duplication
 1
 
4
Deletion
 1
 
4
Duplication
 4
 
4
Deletion
 1
 
4
Deletion
 1
 
4
Deletion-Duplication
 30
 
4
Deletion-Duplication
 3
 

Model Summary

This data reveals an unanticipated role for Uba6 in neuronal development, spine architecture, mouse behavior, and turnover of Ube3a.

References

Type
Title
Author, Year
Primary
Altered social behavior and neuronal development in mice lacking the Uba6-Use1 ubiquitin transfer system.

M_UBA6_1_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exons 16 and 17 of the UBA6 gene, encoding the essential adenylation domain, using Nestin-cre in neuronal, glial and other cell types in the central and peripheral nervous system
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: C57B6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_UBA6_1_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Increased motor coordination indicated by better performance
Exp Paradigm: Rotarod test
 Accelerating rotarod test
 3 months
Grip strength1
Decreased
Description: Decreased grip strength
Exp Paradigm: Grip strength test
 Grip strength test
 3 months
General locomotor activity1
Increased
Description: Increased general locomotory activity indicative of hyperactivity
Exp Paradigm: Open field test
 Open field test
 3 months
Neuronal number: purkinje cells1
Abnormal
Description: Abnormal neuronal architecture in amygdala, reduction in neuronal number in basolateral amygdala and reduced neuronal density in piriform cortex
Exp Paradigm: Hematoxylin and eosin (h&e) staining and immunohistochemistry with neuronal-specific anti-neun antibodies on coronal brain sections
 Histology
 Unreported
Dendritic architecture: spine density1
Decreased
Description: Decreased spine density in amygdala and ca3
Exp Paradigm: Golgi staining
 Golgi-cox staining
 3 months
Brain size1
Decreased
Description: Decreased overall brain size
Exp Paradigm: Brain size measurements
 Histology
 3 months
Neuronal number: purkinje cells1
Abnormal
Description: Abnormal neuronal numbers indicated by reduction in number of neurons in ca3 region with no change in neuronal content in ca1, dentate gyrus, cortex, or cerebellum
Exp Paradigm: Hematoxylin and eosin (h&e) staining and immunohistochemistry with neuronal-specific anti-neun antibodies on coronal brain sections
 Histology
 Unreported
Brain morphology1
Abnormal
Description: Abnormal brain morphology limited specifically to hippocampus and amygdala
Exp Paradigm: Histological analysis of brain sections
 Histology
 3 months
Sensorimotor gating1
Decreased
Description: Decreased prepulse inhibition
Exp Paradigm: Prepulse inhibition test to acoustic stimuli
 Prepulse inhibition
 3 months
Startle response: acoustic stimulus1
Increased
Description: Increased acoustic startle reflex indicated by exaggerated response to acoustic stimuli
Exp Paradigm: Startle sensitivity to acoustic stimuli
 Acoustic startle reflex test
 3 months
Social interaction1
Decreased
Description: Decreased social interactions indicated by less time interacting with stranger mouse preferring empty chamber
Exp Paradigm: Three-chamber social interaction test
 Three-chamber social approach test
 3 months
Nest building behavior1
Decreased
Description: Decreased nest building behavior indicated by no evidence of nest building or interaction with nesting material
Exp Paradigm: Nest building observations
 Nest building assay
 3 months
Metabolic function1
Increased
Description: Increased metabolic activity with more oxygen consumption and carbon dioxide production
Exp Paradigm: Energy homeostasis analysis
 Energy homeostasis analysis
 3 months
Mortality/lethality1
Increased
Description: Increased lethality
Exp Paradigm: General observations
 General observations
 P5-p21, p60
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory indicated by absence of stomach contents
Exp Paradigm: Histological analysis
 Histology
 Unreported
Size/growth1
Decreased
Description: Decreased body weight and body length
Exp Paradigm: General observations
 General observations
 11 weeks
Depression1
Increased
Description: Increased depression indicated by 5-fold less time immobilized
Exp Paradigm: Forced swim test
 Forced swim test
 3 months
Anxiety1
Increased
Description: Increased anxiety demonstrated by more time spent in periphery and less time in center
Exp Paradigm: Open field test
 Open field test
 3 months
Spatial working memory1
Decreased
Description: Decreased working memory indicated by reduced spontaneous alternation
Exp Paradigm: Y-maze arena test
 Y-maze test
 3 months
Cued or contextual fear conditioning1
Increased
Description: Increased cued/conditioning anamolies indicated by reduced freezing to shock and conditioning chamber
Exp Paradigm: Fear-conditioning test
 Fear conditioning test
 3 months
Protein expression level evidence1
Increased
Description: Increased levels of ube3a, arc, and shank3 in amygdala
Exp Paradigm: Spine development protein levels
 Western blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased uba6 protein expression in cortex, hippocampus, and amygdala
Exp Paradigm: Uba6 protein expression
 Western blot
 3 months
Protein expression level evidence1
 No change
 Western blot
 Unreported
Protein expression level evidence1
 No change
 Western blot
 3 months
Core body temperature1
 No change
 NA
 Unreported
Respiratory function1
 No change
 Energy homeostasis analysis
 3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure

 

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