OTUD7AOTU deubiquitinase 7A
Autism Reports / Total Reports
3 / 7Rare Variants / Common Variants
6 / 0Aliases
OTUD7A, C15orf16, C16ORF15, CEZANNE2, OTUD7Associated Syndromes
15q13.3 microdeletion syndromeChromosome Band
15q13.3Associated Disorders
-Relevance to Autism
OTUD7A resides within the locus for 15q13.3 microdeletion syndrome (OMIM 612001). A recurrent 680 kb deletion affecting OTUD7A and CHRNA7 was identified in ten individuals from four unrelated families presenting with neurodevelopmental phenotypes including developmental delay, intellectual disability, and seizures (Shinawi et al., 2009). Two reports published in 2018 further implicated OTUD7A as a major contributor to the phenotypes observed in individuals with 15q13.3 microdeletion syndrome. Uddin et al., 2018 demonstrated that expression of wild-type OTUD7A in cortical neurons from a mouse model of 15q13.3 microdeletion syndrome [Df(h15q13)/+] rescued dendritic spine defects, whereas OTUD7A containing a de novo in-frame deletion variant that was identified in an ASD proband failed to do so. Yin et al., 2018 reported that OTUD7A knockout mice recapitulated many of the the phenotypes observed in Df(h15q13)-/- mice, including developmental delay, abnormal electroencephalography patterns and seizures, rediced ultrasonic vocalizations, impaired motor learning and motor coordination, and reduced acoustic startle.
Molecular Function
The protein encoded by this gene is a deubiquitinizing enzyme with deubiquitinating activity towards 'Lys-11'-linked polyubiquitin chains, as well as a possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression.
External Links
SFARI Genomic Platforms
Reports related to OTUD7A (7 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes | Shinawi M , et al. (2009) | No | - |
2 | Primary | OTUD7A Regulates Neurodevelopmental Phenotypes in the 15q13.3 Microdeletion Syndrome | Uddin M , et al. (2018) | Yes | - |
3 | Recent Recommendation | Otud7a Knockout Mice Recapitulate Many Neurological Features of 15q13.3 Microdeletion Syndrome | Yin J , et al. (2018) | No | - |
4 | Support | Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes | Guo H , et al. (2018) | Yes | - |
5 | Support | - | Kozlova A et al. (2022) | No | - |
6 | Support | - | Zhou X et al. (2022) | Yes | - |
7 | Recent Recommendation | - | Unda BK et al. (2023) | No | - |
Rare Variants (6)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.265C>T | p.Arg89Ter | stop_gained | Unknown | - | - | 35931052 | Kozlova A et al. (2022) | |
c.406G>T | p.Glu136Ter | stop_gained | Unknown | - | - | 35931052 | Kozlova A et al. (2022) | |
c.1474_1482del | p.Ser492_Ser494del | inframe_deletion | Unknown | - | - | 35931052 | Kozlova A et al. (2022) | |
c.1474_1482del | p.Ser492_Ser494del | inframe_deletion | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.2214_2223del | p.Ala739ArgfsTer238 | frameshift_variant | De novo | - | Simplex | 30504930 | Guo H , et al. (2018) | |
c.1474_1482del | p.Asn492_Lys494del | inframe_deletion | De novo | - | Multiplex | 29395074 | Uddin M , et al. (2018) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate
OTUD7A resides within the locus for 15q13.3 microdeletion syndrome (OMIM 612001). A recurrent 680 kb deletion affecting OTUD7A and CHRNA7 was identified in ten individuals from four unrelated families presenting with neurodevelopmental phenotypes including developmental delay, intellectual disability, and seizures (Shinawi et al., 2009). Two reports published in 2018 further implicated OTUD7A as a major contributor to the phenotypes observed in individuals with 15q13.3 microdeletion syndrome. Uddin et al., 2018 demonstrated that expression of wild-type OTUD7A in cortical neurons from a mouse model of 15q13.3 microdeletion syndrome [Df(h15q13)/+] rescued dendritic spine defects, whereas OTUD7A containing a de novo in-frame deletion variant that was identified in an ASD proband failed to do so. Yin et al., 2018 reported that OTUD7A knockout mice recapitulated many of the the phenotypes observed in Df(h15q13)-/- mice, including developmental delay, abnormal electroencephalography patterns and seizures, rediced ultrasonic vocalizations, impaired motor learning and motor coordination, and reduced acoustic startle. Genome sequencing of 180 simplex and multiplex ASD families identified a de novo frameshift variant in the OTUD7A gene in an ASD proband from a simplex family in Guo et al., 2018.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
10/1/2019
Decreased from 3 to 2
New Scoring Scheme
Description
OTUD7A resides within the locus for 15q13.3 microdeletion syndrome (OMIM 612001). A recurrent 680 kb deletion affecting OTUD7A and CHRNA7 was identified in ten individuals from four unrelated families presenting with neurodevelopmental phenotypes including developmental delay, intellectual disability, and seizures (Shinawi et al., 2009). Two reports published in 2018 further implicated OTUD7A as a major contributor to the phenotypes observed in individuals with 15q13.3 microdeletion syndrome. Uddin et al., 2018 demonstrated that expression of wild-type OTUD7A in cortical neurons from a mouse model of 15q13.3 microdeletion syndrome [Df(h15q13)/+] rescued dendritic spine defects, whereas OTUD7A containing a de novo in-frame deletion variant that was identified in an ASD proband failed to do so. Yin et al., 2018 reported that OTUD7A knockout mice recapitulated many of the the phenotypes observed in Df(h15q13)-/- mice, including developmental delay, abnormal electroencephalography patterns and seizures, rediced ultrasonic vocalizations, impaired motor learning and motor coordination, and reduced acoustic startle. Genome sequencing of 180 simplex and multiplex ASD families identified a de novo frameshift variant in the OTUD7A gene in an ASD proband from a simplex family in Guo et al., 2018.
Reports Added
[New Scoring Scheme]10/1/2018
Decreased from 3 to 3
Description
OTUD7A resides within the locus for 15q13.3 microdeletion syndrome (OMIM 612001). A recurrent 680 kb deletion affecting OTUD7A and CHRNA7 was identified in ten individuals from four unrelated families presenting with neurodevelopmental phenotypes including developmental delay, intellectual disability, and seizures (Shinawi et al., 2009). Two reports published in 2018 further implicated OTUD7A as a major contributor to the phenotypes observed in individuals with 15q13.3 microdeletion syndrome. Uddin et al., 2018 demonstrated that expression of wild-type OTUD7A in cortical neurons from a mouse model of 15q13.3 microdeletion syndrome [Df(h15q13)/+] rescued dendritic spine defects, whereas OTUD7A containing a de novo in-frame deletion variant that was identified in an ASD proband failed to do so. Yin et al., 2018 reported that OTUD7A knockout mice recapitulated many of the the phenotypes observed in Df(h15q13)-/- mice, including developmental delay, abnormal electroencephalography patterns and seizures, rediced ultrasonic vocalizations, impaired motor learning and motor coordination, and reduced acoustic startle. Genome sequencing of 180 simplex and multiplex ASD families identified a de novo frameshift variant in the OTUD7A gene in an ASD proband from a simplex family in Guo et al., 2018.
7/1/2018
Increased from to 3
Description
OTUD7A resides within the locus for 15q13.3 microdeletion syndrome (OMIM 612001). A recurrent 680 kb deletion affecting OTUD7A and CHRNA7 was identified in ten individuals from four unrelated families presenting with neurodevelopmental phenotypes including developmental delay, intellectual disability, and seizures (Shinawi et al., 2009). Two reports published in 2018 further implicated OTUD7A as a major contributor to the phenotypes observed in individuals with 15q13.3 microdeletion syndrome. Uddin et al., 2018 demonstrated that expression of wild-type OTUD7A in cortical neurons from a mouse model of 15q13.3 microdeletion syndrome [Df(h15q13)/+] rescued dendritic spine defects, whereas OTUD7A containing a de novo in-frame deletion variant that was identified in an ASD proband failed to do so. Yin et al., 2018 reported that OTUD7A knockout mice recapitulated many of the the phenotypes observed in Df(h15q13)-/- mice, including developmental delay, abnormal electroencephalography patterns and seizures, rediced ultrasonic vocalizations, impaired motor learning and motor coordination, and reduced acoustic startle.
Krishnan Probability Score
Score 0.46138310282127
Ranking 9383/25841 scored genes
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ExAC Score
Score 0.97459544138619
Ranking 2261/18225 scored genes
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Sanders TADA Score
Score 0.94284890471288
Ranking 15462/18665 scored genes
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Zhang D Score
Score 0.53701356720806
Ranking 299/20870 scored genes
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CNVs associated with OTUD7A(1 CNVs)
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15q13.3 | 80 | Deletion-Duplication | 117 / 452 |