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Intellectual disability

Gene: OTUD7A

Green List (high evidence)
OTUD7A (OTU deubiquitinase 7A)
EnsemblGeneIds (GRCh38): ENSG00000169918
EnsemblGeneIds (GRCh37): ENSG00000169918
OMIM: 612024, Gene2Phenotype
OTUD7A is in 3 panels

6 reviews

Eleanor Williams (Genomics England Curator)

This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:31997314 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag
Created: 16 Oct 2023, 8:04 p.m. | Last Modified: 16 Oct 2023, 8:04 p.m.
Panel Version: 5.313
Created: 16 Oct 2023, 8:04 p.m.
Last Modified: 16 Oct 2023, 8:04 p.m.
Panel version: 5.313

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 11 Oct 2023, 9:34 a.m.
Last Modified: 11 Oct 2023, 9:34 a.m.
Panel version: 5.286

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Created: 17 Apr 2023, 6:19 a.m. | Last Modified: 17 Apr 2023, 6:19 a.m.
Panel Version: 5.50
PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.

This gene has been reported in the DD panel of Gene2Phenotype (with 'limited' rating), but has not yet been associated with phenotypes in OMIM.
Created: 17 Apr 2023, 6:12 a.m. | Last Modified: 17 Apr 2023, 6:30 a.m.
Panel Version: 5.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intellectual disability, MONDO:0001071

Publications

Created: 17 Apr 2023, 6:12 a.m.
Last Modified: 17 Apr 2023, 6:30 a.m.
Panel version: 5.47

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

Second case and third case with DD and biallelic variant reported in 36180924 and 31997314, in addition to the previously mentioned 31997314.
Created: 8 Oct 2022, 10:59 p.m. | Last Modified: 8 Oct 2022, 10:59 p.m.
Panel Version: 3.1737

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 8 Oct 2022, 10:59 p.m.
Last Modified: 8 Oct 2022, 10:59 p.m.
Panel version: 3.1737

Sarah Leigh (Genomics England Curator)

Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen, Although the region ISCA-46295-Loss, which encompasses the OTUD7A locus, is associated with seizures 20236110, mental retardation 22775350, dysmorphic features, developmental delay and severe epileptic encephalopathy. PMID 31997314 report a homozygous variant in a case of severe global developmental delay, language impairment and epileptic encephalopathy; segregation and functional studies support this gene disease association.
Created: 2 Jul 2020, 5:07 p.m. | Last Modified: 2 Jul 2020, 5:07 p.m.
Panel Version: 3.132
Created: 2 Jul 2020, 5:07 p.m.
Last Modified: 2 Jul 2020, 5:07 p.m.
Panel version: 3.132

Zornitza Stark (Australian Genomics)

Red List (low evidence)

One patient with severe global developmental delay, language impairment and epileptic encephalopathy reported. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies. Mouse model and other data support the role of this gene in neurodevelopmental phenotypes but nevertheless, single family to date.
Sources: Literature
Created: 4 Jun 2020, 2:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, intellectual disability, no OMIM# yet

Publications

Created: 4 Jun 2020, 2:42 a.m.

Panel version: 3.80

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • developmental and epileptic encephalopathy, MONDO:0100062
  • intellectual disability, MONDO:0001071
OMIM
612024
Clinvar variants
Variants in OTUD7A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Apr 2024, Gel status: 3

Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag gene-checked was removed from gene: OTUD7A.

16 Oct 2023, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag gene-checked tag was added to gene: OTUD7A.

11 Oct 2023, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, intellectual disability, no OMIM# yet to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071

11 Oct 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_23_promote_green was removed from gene: OTUD7A.

11 Oct 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to OTUD7A. Source Expert Review Green was added to OTUD7A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_23_promote_green tag was added to gene: OTUD7A.

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: otud7a has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924

17 Apr 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074

2 Jul 2020, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: otud7a has been classified as Red List (Low Evidence).

4 Jun 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: OTUD7A was added gene: OTUD7A was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074 Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, intellectual disability, no OMIM# yet Review for gene: OTUD7A was set to RED