Human Gene Module / Chromosome 15 / UBE3A

UBE3Aubiquitin protein ligase E3A

Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
7 / 27
Rare Variants / Common Variants
19 / 2
Aliases
UBE3A, AS,  ANCR,  E6-AP,  HPVE6A,  EPVE6AP,  FLJ26981
Associated Syndromes
Angelman syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association
Chromosome Band
15q11.2
Associated Disorders
EPS, ID, ASD, ADHD, DD/NDD
Relevance to Autism

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.

Reports related to UBE3A (27 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families. Nurmi EL , et al. (2001) Yes -
2 Recent Recommendation Imprinting in neurons. Kishino T (2006) No -
3 Recent Recommendation Ube3a expression is not altered in Mecp2 mutant mice. Jordan C and Francke U (2006) No -
4 Recent Recommendation Gene symbol: UBE3A. Disease: Angelman syndrome. Mueller OT and Coovadia A (2008) No -
5 Support Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Glessner JT , et al. (2009) Yes -
6 Recent Recommendation Ube3a is required for experience-dependent maturation of the neocortex. Yashiro K , et al. (2009) No -
7 Support Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Schaaf CP , et al. (2011) Yes -
8 Support High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism. Kelleher RJ 3rd , et al. (2012) Yes -
9 Recent Recommendation Impairment of TrkB-PSD-95 signaling in Angelman syndrome. Cao C , et al. (2013) No -
10 Recent Recommendation E6AP/UBE3A ubiquitin ligase harbors two E2~ubiquitin binding sites. Ronchi VP , et al. (2013) No -
11 Recent Recommendation Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc. Khnle S , et al. (2013) No -
12 Support Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Carvill GL , et al. (2013) No ID, ASD, DD
13 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
14 Support Whole-genome sequencing of quartet families with autism spectrum disorder. Yuen RK , et al. (2015) Yes -
15 Recent Recommendation A coding-independent function of an alternative Ube3a transcript during neuronal development. Valluy J , et al. (2015) No -
16 Support 15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes. Noor A , et al. (2015) No Neuropsychiatric phenotypes (anxiety, depression)
17 Recent Recommendation UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis. Sun J , et al. (2015) No -
18 Recent Recommendation An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A. Yi JJ , et al. (2015) No -
19 Recent Recommendation Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila. Li W , et al. (2016) No -
20 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. Martnez F , et al. (2016) No ID
21 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Trujillano D , et al. (2016) No DD, epilepsy/seizures
22 Support Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes. Parrini E , et al. (2016) No Angelman syndrome
23 Support The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/-catenin pathway by inhibiting the proteasome. Yi JJ , et al. (2017) No -
24 Support Expanding the genetic heterogeneity of intellectual disability. Anazi S , et al. (2017) No -
25 Support Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice. Tumien B , et al. (2017) No ADHD
26 Support Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes. Xiong J , et al. (2019) Yes ID
27 Highly Cited UBE3A/E6-AP mutations cause Angelman syndrome. Kishino T , et al. (1997) No -
Rare Variants   (19)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.601G>A;c.532G>A;c.592G>A p.Ala201Thr;p.Ala178Thr;p.Ala198Thr missense_variant Familial (5 cases), Unknown (5 cases) Maternal (3 cases); paternal (2 cases) Simplex 21624971 Schaaf CP , et al. (2011)
c.520A>G p.Thr174Ala missense_variant Unknown - Simplex 21624971 Schaaf CP , et al. (2011)
c.571_579delCTTTTC p.192_193del inframe_deletion Familial Paternal Simplex 21624971 Schaaf CP , et al. (2011)
c.333C>G p.Asn111Lys missense_variant - - Multiplex 22558107 Kelleher RJ 3rd , et al. (2012)
c.1269C>T p.(=) synonymous_variant - - Multiplex 22558107 Kelleher RJ 3rd , et al. (2012)
c.1585G>A p.Arg506Cys missense_variant Familial Maternal Multiplex 23708187 Carvill GL , et al. (2013)
c.2110G>C p.Pro704Ala missense_variant Unknown - - 23708187 Carvill GL , et al. (2013)
- p.Thr485Ala missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.1796delC p.Ala599fs frameshift_variant Familial Maternal Multiplex 25621899 Yuen RK , et al. (2015)
- - copy_number_gain Familial Maternal Multi-generational 25884337 Noor A , et al. (2015)
c.2609G>A p.Gly870Asp missense_variant De novo Germinal mosaicism Multiplex 27620904 Martnez F , et al. (2016)
c.2572_2575dup p.Lys859ThrfsTer2 frameshift_variant De novo - - 27848944 Trujillano D , et al. (2016)
c.947T>C p.Leu293Pro missense_variant De novo - - 27864847 Parrini E , et al. (2016)
c.312_315del p.Tyr104Ter frameshift_variant De novo - - 27864847 Parrini E , et al. (2016)
c.504delG p.Val170LeufsTer9 frameshift_variant - - Multiplex 28940097 Anazi S , et al. (2017)
c.2513_2525dupCTACATCTCATAC p.Cys843fs frameshift_variant De novo - - 29286531 Tumien B , et al. (2017)
c.2281G>A p.Gly761Arg missense_variant De novo - - 29286531 Tumien B , et al. (2017)
c.2507_2510delAAGA p.Lys836Argfs frameshift_variant De novo - - 31031587 Xiong J , et al. (2019)
c.1437C>A p.Tyr479Ter stop_gained De novo - - 31031587 Xiong J , et al. (2019)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - microsatellite - - - 11543639 Nurmi EL , et al. (2001)
- - copy_number_gain - - - 19404257 Glessner JT , et al. (2009)
SFARI Gene score
3S

Suggestive Evidence, Syndromic

3S

Score Delta: Increased from 3S to 4.5 + acc2 + S

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2018
3S
icon
4.5 + acc2 + S

Increased from 3S to 4.5 + acc2 + S

Description

3S

10/1/2017
3S
icon
3S

Increased from 3S to 3S

Description

UBE3A is present in common 15q11-13 duplications which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). Angelman syndrome results predominantly either from de novo 15q11-q13 deletions on the maternal chromosome or mutations in UBE3A. A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 found novel coding variants but was not statistically strong in a case-control study. Kim et al., 2008 failed to find association in TdT tests. Nurmi et al., reported a preliminary study of association (2003). Veenstra-VanderWeele reported rare variants with resequencing in 1999, but with no case-control sequencing. A de novo missense variant in UBE3A (p.Thr485Ala) that was identified in a male ASD proband from the Simons Simplex Collection in PMID 25363768 was demonstrated in PMID 26255772 to abolish a phosphorylation site involved in regulating UBE3A activity. As a result of this variant, mutant UBE3A showed enhanced UBE3A activity in vitro and enhanced substrate turnover, which in turn caused excessive dendritic spine development in vivo. Increased UBE3A gene dosage in mice resulted in defective social interaction, impaired communication, and increased repetitive stereotypic behavior in PMID 21974935.

4/1/2017
3S
icon
3S

Increased from 3S to 3S

Description

UBE3A is present in common 15q11-13 duplications which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). Angelman syndrome results predominantly either from de novo 15q11-q13 deletions on the maternal chromosome or mutations in UBE3A. A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 found novel coding variants but was not statistically strong in a case-control study. Kim et al., 2008 failed to find association in TdT tests. Nurmi et al., reported a preliminary study of association (2003). Veenstra-VanderWeele reported rare variants with resequencing in 1999, but with no case-control sequencing. A de novo missense variant in UBE3A (p.Thr485Ala) that was identified in a male ASD proband from the Simons Simplex Collection in PMID 25363768 was demonstrated in PMID 26255772 to abolish a phosphorylation site involved in regulating UBE3A activity. As a result of this variant, mutant UBE3A showed enhanced UBE3A activity in vitro and enhanced substrate turnover, which in turn caused excessive dendritic spine development in vivo. Increased UBE3A gene dosage in mice resulted in defective social interaction, impaired communication, and increased repetitive stereotypic behavior in PMID 21974935.

Reports Added
[Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.2001] [Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.2009] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.2012] [UBE3A/E6-AP mutations cause Angelman syndrome.1997] [Imprinting in neurons.2006] [Ube3a expression is not altered in Mecp2 mutant mice.2006] [Gene symbol: UBE3A. Disease: Angelman syndrome.2008] [Ube3a is required for experience-dependent maturation of the neocortex.2009] [Impairment of TrkB-PSD-95 signaling in Angelman syndrome.2013] [E6AP/UBE3A ubiquitin ligase harbors two E2~ubiquitin binding sites.2013] [Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc.2013] [A coding-independent function of an alternative Ube3a transcript during neuronal development.2015] [15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes.2015] [UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis.2015] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A.2015] [Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila.2016] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/-catenin pathway by inhibiting the proteasome.2017]
1/1/2017
3S
icon
3S

Increased from 3S to 3S

Description

UBE3A is present in common 15q11-13 duplications which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). Angelman syndrome results predominantly either from de novo 15q11-q13 deletions on the maternal chromosome or mutations in UBE3A. A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 found novel coding variants but was not statistically strong in a case-control study. Kim et al., 2008 failed to find association in TdT tests. Nurmi et al., reported a preliminary study of association (2003). Veenstra-VanderWeele reported rare variants with resequencing in 1999, but with no case-control sequencing. A de novo missense variant in UBE3A (p.Thr485Ala) that was identified in a male ASD proband from the Simons Simplex Collection in PMID 25363768 was demonstrated in PMID 26255772 to abolish a phosphorylation site involved in regulating UBE3A activity. As a result of this variant, mutant UBE3A showed enhanced UBE3A activity in vitro and enhanced substrate turnover, which in turn caused excessive dendritic spine development in vivo. Increased UBE3A gene dosage in mice resulted in defective social interaction, impaired communication, and increased repetitive stereotypic behavior in PMID 21974935.

10/1/2016
3S
icon
3S

Increased from 3S to 3S

Description

UBE3A is present in common 15q11-13 duplications which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). Angelman syndrome results predominantly either from de novo 15q11-q13 deletions on the maternal chromosome or mutations in UBE3A. A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 found novel coding variants but was not statistically strong in a case-control study. Kim et al., 2008 failed to find association in TdT tests. Nurmi et al., reported a preliminary study of association (2003). Veenstra-VanderWeele reported rare variants with resequencing in 1999, but with no case-control sequencing. A de novo missense variant in UBE3A (p.Thr485Ala) that was identified in a male ASD proband from the Simons Simplex Collection in PMID 25363768 was demonstrated in PMID 26255772 to abolish a phosphorylation site involved in regulating UBE3A activity. As a result of this variant, mutant UBE3A showed enhanced UBE3A activity in vitro and enhanced substrate turnover, which in turn caused excessive dendritic spine development in vivo. Increased UBE3A gene dosage in mice resulted in defective social interaction, impaired communication, and increased repetitive stereotypic behavior in PMID 21974935.

4/1/2016
3S
icon
3S

Increased from 3S to 3S

Description

UBE3A is present in common 15q11-13 duplications which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). Angelman syndrome results predominantly either from de novo 15q11-q13 deletions on the maternal chromosome or mutations in UBE3A. A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 found novel coding variants but was not statistically strong in a case-control study. Kim et al., 2008 failed to find association in TdT tests. Nurmi et al., reported a preliminary study of association (2003). Veenstra-VanderWeele reported rare variants with resequencing in 1999, but with no case-control sequencing. A de novo missense variant in UBE3A (p.Thr485Ala) that was identified in a male ASD proband from the Simons Simplex Collection in PMID 25363768 was demonstrated in PMID 26255772 to abolish a phosphorylation site involved in regulating UBE3A activity. As a result of this variant, mutant UBE3A showed enhanced UBE3A activity in vitro and enhanced substrate turnover, which in turn caused excessive dendritic spine development in vivo. Increased UBE3A gene dosage in mice resulted in defective social interaction, impaired communication, and increased repetitive stereotypic behavior in PMID 21974935.

Reports Added
[Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.2001] [Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.2009] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.2012] [UBE3A/E6-AP mutations cause Angelman syndrome.1997] [Imprinting in neurons.2006] [Ube3a expression is not altered in Mecp2 mutant mice.2006] [Gene symbol: UBE3A. Disease: Angelman syndrome.2008] [Ube3a is required for experience-dependent maturation of the neocortex.2009] [Impairment of TrkB-PSD-95 signaling in Angelman syndrome.2013] [E6AP/UBE3A ubiquitin ligase harbors two E2~ubiquitin binding sites.2013] [Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc.2013] [A coding-independent function of an alternative Ube3a transcript during neuronal development.2015] [15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes.2015] [UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis.2015] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A.2015] [Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila.2016]
7/1/2015
S
icon
3S

Increased from S to 3S

Description

UBE3A is present in common 15q11-13 duplications which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). Angelman syndrome results predominantly either from de novo 15q11-q13 deletions on the maternal chromosome or mutations in UBE3A. A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 found novel coding variants but was not statistically strong in a case-control study. Kim et al., 2008 failed to find association in TdT tests. Nurmi et al., reported a preliminary study of association (2003). Veenstra-VanderWeele reported rare variants with resequencing in 1999, but with no case-control sequencing. A de novo missense variant in UBE3A (p.Thr485Ala) that was identified in a male ASD proband from the Simons Simplex Collection in PMID 25363768 was demonstrated in PMID 26255772 to abolish a phosphorylation site involved in regulating UBE3A activity. As a result of this variant, mutant UBE3A showed enhanced UBE3A activity in vitro and enhanced substrate turnover, which in turn caused excessive dendritic spine development in vivo. Increased UBE3A gene dosage in mice resulted in defective social interaction, impaired communication, and increased repetitive stereotypic behavior in PMID 21974935.

Reports Added
[Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.2001] [Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.2009] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.2012] [UBE3A/E6-AP mutations cause Angelman syndrome.1997] [Imprinting in neurons.2006] [Ube3a expression is not altered in Mecp2 mutant mice.2006] [Gene symbol: UBE3A. Disease: Angelman syndrome.2008] [Ube3a is required for experience-dependent maturation of the neocortex.2009] [Impairment of TrkB-PSD-95 signaling in Angelman syndrome.2013] [E6AP/UBE3A ubiquitin ligase harbors two E2~ubiquitin binding sites.2013] [Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc.2013] [A coding-independent function of an alternative Ube3a transcript during neuronal development.2015] [15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes.2015] [UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis.2015] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A.2015]
4/1/2015
S
icon
S

Increased from S to S

Description

Present in common 15q11-13 duplication which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 find novel coding variants but not statistically strong in case-control study. Kim et al., 2008 fail to find association in TdT tests. Nurmi et al., report prelim study of association (2003). Veenstra-VanderWeele reports rare variants with resequencing in 1999. No case-control sequencing.

1/1/2015
S
icon
S

Increased from S to S

Description

Present in common 15q11-13 duplication which involves autism (Glessner et al., 2009; Bucan et al., 2009 and many other references reporting duplication). A number of other rare variants which have been associated with this gene and/or association studies without sufficient statistical significance to warrant elevating the gene. Schaaf et al., 2011 find novel coding variants but not statistically strong in case-control study. Kim et al., 2008 fail to find association in TdT tests. Nurmi et al., report prelim study of association (2003). Veenstra-VanderWeele reports rare variants with resequencing in 1999. No case-control sequencing.

Krishnan Probability Score

Score 0.57047232918466

Ranking 917/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.9995762439583

Ranking 899/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.93793256990487

Ranking 13691/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score

Score -0.10514181672056

Ranking 12541/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
CNVs associated with UBE3A(1 CNVs)
15q11.2 88 Deletion-Duplication 126  /  2155
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
AFG3L1P AFG3-like AAA ATPase 1, pseudogene Human Protein Binding 172
AHSP alpha hemoglobin stabilizing protein Human Protein Binding 51327 Q549J4
ANXA1 annexin A1 Human Protein Binding 301 P04083
Arc activity regulated cytoskeletal-associated protein Mouse Protein Binding 11838 Q9WV31
Arhgef15 Rho guanine nucleotide exchange factor (GEF) 15 Mouse Protein Binding 442801 Q5FWH6
ASAP3 ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 Human Protein Binding 55616 Q8TDY4
BMAL1 Aryl hydrocarbon receptor nuclear translocator-like protein 1 Human Protein Binding 406 O00327
BPY2 basic charge, Y-linked, 2 Human Protein Binding 9083 O14599
CELA2B Chymotrypsin-like elastase family member 2B Human Protein Binding 51032 P08218
CG8209 Fruit Fly Protein Binding 38888 Q9VSC5
DERA deoxyribose-phosphate aldolase (putative) Human Protein Binding 51071 Q9Y315
ERCC6L2 excision repair cross-complementing rodent repair deficiency, complementation group 6-like 2 Human Protein Binding 375748 Q5T890
Kcnn2 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 Mouse Protein Binding 140492 P58390
KLHL38 kelch-like family member 38 Human Protein Binding 340359 Q2WGJ6
MAGEA8 melanoma antigen family A8 Human Protein Binding 4107 B2R9W4
miR-134 microRNA 134 Human RNA Binding 406924 N/A
PIPSL PIP5K1A and PSMD4-like, pseudogene Human Protein Binding 266971 A2A3N6
PSMB7 proteasome (prosome, macropain) subunit, beta type, 7 Human Protein Binding 5695 E9KL30
Rpn10 26S proteasome non-ATPase regulatory subunit 4 Fruit Fly Protein Binding 40388 P55035
SERHL2 Serine hydrolase-like protein 2 Human Protein Binding 253190 Q9H4I8
SHBG sex hormone-binding globulin Human Protein Binding 6462 P04278
TRPV5 Transient receptor potential cation channel subfamily V member 5 Human Protein Binding 56302 E9PBZ6
Uch-L5 Ubiquitin C-terminal hydrolase Fruit Fly Protein Binding 39102 Q9XZ61
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