Studies have found genetic association and rare variations in the UBE3A gene that are associated with autism. Association was found in families of the Collaborative Linkage Study of Autism (Nurmi et al., 2001), and rare variants were found in cases of European ancestry.
Molecular Function
This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.
A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome
Dube3a null mutants display abnormal locomotive behavior and circadian rhythms, and defective long-term memory. Flies that overexpress Ube3a in the nervous system also display locomotion defects, dependent on the ubiquitin ligase activity. Missense mutations in UBE3A alleles of Angelman syndrome patients alter amino acid residues conserved in the fly protein, and when introduced into dube3a, behave as loss-of-function mutations. Loss of function of Ube3a leads to climbing defects and overexpression causes changes in synaptic transmission in the neuromuscular junction. Ube3a mutants also show reduced gene and protein expression of Ube3a, an effect more pronounced in mutants with paternally inherited null mutation. Knockout and knockdown mutants show learning deficits which can be rescued by reexpression of genomic or human variant of Ube3a. The learning deficits are not due to locomotor activity ot taste sensitivity impairments as those are not affected in mutants.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies overexpressing the dube3a^C941A UAS transgene with the eye-specific Gal4 driver, GMR-gal4.
Allele Type: Loss-of-function
Strain of Origin: w; dube3a^C941A
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies overexpressing the wildtype dube3a UAS transgene with the eye-specific Gal4 driver, GMR-gal4.
Allele Type: LOF Knockin
Strain of Origin: w; dube3a^15B
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies that overexpress dube3a^C941A in the developing and adult nervous system were generated using the Gal4/UAS system and the pan-neural driver elav-gal4.
Allele Type: LOF Knockin
Strain of Origin: w; dube3a^C941A
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies that overexpress dube3a in the wing were generated using the Gal4/UAS system and the wing driver MS1096-gal4.
Allele Type: Overexpression
Strain of Origin: dube3a
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies that overexpress dube3a^C941A in the wing were generated using the Gal4/UAS system and the wing driver MS1096-gal4.
Allele Type: Overexpression
Strain of Origin: w; dube3a^C941A
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies that ubiquitously overexpress dube3a^C941A using the Gal4/UAS system and the ubiquitous driver tubulin4-gal4.
Allele Type: Overexpression
Strain of Origin: w; dube3a^C941A
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (C55Y) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the eye using the GMR-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^C55Y
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (T447P) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the eye using the GMR-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^T447P
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (R626) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the eye using the GMR-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^R626C
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
dube3a^80 mutant line was generated by modifying another dube3A mutant line carrying a transposable P element inserted in the 5'UTR of the dube3A gene, by immobilizing the P element to generate an imprecise excision or deletion allele. The transcription start site is within the deletion in dube3a^80, yielding no dube3a80 transcripts. dube3a^6PE is a precise excision (WT) allele that is isogenic with dube3a^15B for the two major autosomes and was used as control. .
Allele Type: Knockout
Strain of Origin: w; dube3a^80
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (I925K) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the eye using the GMR-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^I925K
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (C55Y) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the wing using the MS1096--GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^C55Y
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (T447P) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the wing using the MS1096--GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^T447P
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (R626) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the wing using the MS1096--GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^R626C
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (I925K) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients selectively overexpressed in the wing using the MS1096--GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^I925K
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (C55Y) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients ubiquitously overexpressed in the fly using the tubulin4-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^C55Y
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (T447P) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients ubiquitously overexpressed in the fly using the tubulin4-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^T447P
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (R626) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients ubiquitously overexpressed in the fly using the tubulin4-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^R626C
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies with a missense mutation of human UBE3A (I925K) introduced into the fly 3mdube3a gene that results in loss of function and has been identified in Angelman syndrome patients ubiquitously overexpressed in the fly using the tubulin4-GAL4 driver.
Allele Type: LOF Knockin
Strain of Origin: w; UASt-3myc dube3a^I925K
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
dube3a^6J mutant line was generated by modifying another dube3A mutant line carrying a transposable P element inserted in the 5'UTR of the dube3A gene, by immobilizing the P element to generate an imprecise excision or deletion allele. The mutant allele retains the transcription start site and yields transcripts containing exons downstream of the deletion. dube3a^6PE is a precise excision (WT) allele that is isogenic with dube3a^15B for the two major autosomes and was used as control. .
Allele Type: Knockout
Strain of Origin: w; dube3a^6J
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies overexpressing the dube3a^C941A UAS transgene with the eye-specific Gal4 driver, GMR-gal4.
Allele Type: LOF Knockin
Strain of Origin: w; dube3a^C941A
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
dube3a^15B null mutant line was generated by modifying another dube3A mutant line carrying a transposable P element inserted in the 5'UTR of the dube3A gene, by immobilizing the P element to generate an imprecise excision or deletion allele. The mutant allele retains the transcription start site and yields transcripts containing exons downstream of the deletion. dube3a^6PE is a precise excision (WT) allele that is isogenic with dube3a^15B for the two major autosomes and was used as control. .
Allele Type: Knockout
Strain of Origin: w; dube3a^15B
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies that overexpress dube3a in the developing and adult nervous system were generated using the Gal4/UAS system and the pan-neural driver elav-gal4.
Allele Type: Overexpression
Strain of Origin: dube3a
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Transheterozygotes of dube3a^80 and Df(3L)vin5, a chromosome that carries a deletion of several genes including dube3a. .
Allele Type: Knockout
Strain of Origin: w; dube3a^80
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Transheterozygotes of dube3a^6J and Df(3L)vin5, a chromosome that carries a deletion of several genes including dube3a. .
Allele Type: Knockout
Strain of Origin: w; dube3a^6J
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Transheterozygotes of dube3a^15B and Df(3L)vin5, a chromosome that carries a deletion of several genes including dube3a. .
Allele Type: Knockout
Strain of Origin: w; dube3a^15B
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Transheterozygotes of dube3a^6PE and Df(3L)vin5, a chromosome that carries a deletion of several genes including dube3a. .
Allele Type: Knockout
Strain of Origin: w; dube3a^6PE
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Flies that ubiquitously overexpress dube3a using the Gal4/UAS system and the ubiquitous driver tubulin4-gal4.
Allele Type: Overexpression
Strain of Origin: dube3a
Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mutant Ube3a allele, with a P transposable element, inherited maternally.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mutant Ube3a allele, with a P transposable element, inherited paternally.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Duplication mutation inherited maternally.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Duplication mutation inherited paternally.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Homozygous duplication mutation.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
ElavGal4 driven expression of UASdube3aRNAi (w^1118; P{GD450}v45876) in neurons in a wildtype background.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 45876
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
ElavGal4 driven expression of UASdube3aRNAi (w^1118; P{GD450}v45875) in neurons in a wildtype background.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: VDRC 45875
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
ElavGal4 driven overexpression of UASdube3a in wild-type background.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
ElavGal4 driven overexpression of human Ube3a isoform 1 (2558bp) in wild-type background.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
ElavGal4 driven overexpression of UASdube3aC941A in wild-type background.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
201YGal4 driven expression of UASdube3aRNAi's (w^1118; P{GD450}v45876 and w^1118; P{GD450}v45875) in in maternally-inherited null mutation background.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
OK107Gal4 driven expression of UASdube3aRNAi's (w^1118; P{GD450}v45876 and w^1118; P{GD450}v45875) in in maternally-inherited null mutation background.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Mutant Ube3a allele, with a P transposable element, inherited maternally.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional silencing using temperature-sensitive tubulin-Gal80 from egg to 3 days of age.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional silencing using temperature-sensitive tubulin-Gal80 from eclosion to 3 days of age.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional silencing using temperature-sensitive tubulin-Gal80 from egg to eclosion.
Allele Type: Loss-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Knockdown of Dube3a using dsRNAi in the embryonic and larval somatic muscle using the 24B-Gal4 driver.
Allele Type: Knockdown
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Knockdown of Dube3a using dsRNAi in muscle or neurons using the pan neuronal driver c155-Gal4.
Allele Type: Knockdown
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Fruitfly Dube3a (Ube3a)line that produces the highest Dube3a protein levels (compared to line 51 and 45) under the pan neuronal C155-Gal4 driver. Authors note that this transgene manifests a rough eye with the eye specific gmr-Gal4 driver.
Allele Type: Overexpression
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Fruitfly Dube3a (Ube3a)line that produces a moderate increase in Dube3a protein levels under the C155-Gal4 pan neuronal driver (authors note that this transgene manifests a mildly rough eye with the eye specific gmr-Gal4 driver).
Allele Type: Overexpression
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Fruitfly Dube3a (Ube3a)line that produces a moderate increase in Dube3a protein levels under the C155-Gal4 pan neuronal driver (authors note that this transgene manifests a mildly rough eye with the eye specific gmr-Gal4 driver).
Allele Type: Overexpression
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Knockdown of Dube3a using dsRNAi in embryonic mesoderm, larval muscles and wing imaginal discs using c179-Gal4 driver.
Allele Type: Knockdown
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Dube3a^15b a loss of function mutation resulting in no Dube3a protein.
Allele Type: Knockout
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Knockdown of Dube3a usind dsRNAi in the somatic muscle and imaginal wing discs using the mef2-Gal4 driver.
Allele Type: Knockdown
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
.
Allele Type: Knockout
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source: Bloomington Drosophila Stock Center
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
.
Allele Type: Knockdown
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source: Bloomington Drosophila Stock Center
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
.
Allele Type: Knockdown
Strain of Origin: Genetic Background: w^1118
ES Cell Line: Mutant ES Cell Line: Model Source: Ronald L. Davis (The Scripps Research Institute, Jupiter, FL)
Description: Mutants showed some abnormalities in eye development compared to controls. Five out of six lines had normal eye development, however one line showed development of rough eyes.
Description: Mutant fly eyes show variable accumulation of mutant protein compared to controls. One of six line shows no change in mutant protein accumulation compared to controls.
Description: Mutant flies showed some increase in lethality compared to controls. Four out of six lines showed no difference in lethality, however two lines showed an increased in lethality compared to controls.
Description: Young male mutant flies showed weaker circadian rhythm strength compared to controls.
Exp Paradigm: The relative power of rhythmicity was indicated as a Fast Fourier Transformation (FFT) value. Flies were entrained to a 12 h:12 h, light:dark cycle for 3 days.
Description: Older male mutant flies showed weaker circadian rhythm strength compared to controls.
Exp Paradigm: The relative power of rhythmicity was indicated as a Fast Fourier Transformation (FFT) value. Flies were entrained to a 12 h:12 h, light:dark cycle for 3 days.
Description: Older female mutant flies showed weaker circadian rhythm strength compared to controls.
Exp Paradigm: The relative power of rhythmicity was indicated as a Fast Fourier Transformation (FFT) value. Flies were entrained to a 12 h:12 h, light:dark cycle for 3 days.
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Mutant flies showed deficits in avoiding an odor associated to footshock in spaced training paradigm but not in mass training paradigm compared to controls.
Exp Paradigm: Spaced training: 10 training sessions (12 trials per session) are separated by 15-min rest intervals. Flies were trained to associate an odor with a shock and were then tested for avoidance of the odor.
Description: Overexpression of Dube3a causes decreased EJP as in several transgenic larvae it could not be evoked at intermittent time points
Exp Paradigm: Rapid Stimulation Assay
Description: Amplitude of EJPs evoked following rapid stimulation decreases in Dube3a deficient larvae compared to WT in rapid stimulation assays
Exp Paradigm: Rapid Stimulation Assay
Description: Resting membrane potential of Dube3a 15b (Dube3a deficient) muscle cells is significantly more negative compared to w118 indicating hyperpolarization of membrane
