OTUD7A

OTU deubiquitinase 7A, the group of OTU domain containing

Basic information

Region (hg38): 15:31475398-31870789

Previous symbols: [ "C15orf16", "OTUD7" ]

Links

ENSG00000169918 ∙ NCBI:161725 ∙ OMIM:612024 ∙ HGNC:20718 ∙ Uniprot:Q8TE49 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia and seizures	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	33381903; 31997314
Heterozygotes are described as manifesting with milder neurocognitive sequelae

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OTUD7A gene.

• Specific learning disability (1 variants)
• Neurodevelopmental disorder with hypotonia and seizures (1 variants)
• Language disorder;Epileptic encephalopathy;Severe global developmental delay (1 variants)
• Non-syndromic intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTUD7A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	4	12
missense	1		54	1	1	57
nonsense	1		1			2
start loss						0
frameshift			4			4
inframe indel			1	1	1	3
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding					1	1
Total	2	1	60	10	7

Variants in OTUD7A

This is a list of pathogenic ClinVar variants found in the OTUD7A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-31483301-C-T		not specified	Uncertain significance (May 24, 2024)
15-31483422-G-A		not specified	Uncertain significance (Jun 05, 2023)
15-31483428-G-C		not specified	Uncertain significance (Apr 08, 2023)
15-31483431-C-T		not specified	Uncertain significance (Jun 13, 2024)
15-31483449-C-G		See cases	Uncertain significance (Nov 04, 2020)
15-31483457-C-G		not specified	Uncertain significance (Apr 13, 2022)
15-31483468-C-CGCGTCG			Uncertain significance (Apr 26, 2022)
15-31483512-A-G		not specified	Uncertain significance (Jun 12, 2023)
15-31483519-G-C			Likely benign (Feb 01, 2024)
15-31483548-C-T		not specified	Uncertain significance (Dec 11, 2023)
15-31483557-T-C		not specified	Likely benign (Apr 12, 2023)
15-31483580-C-G		not specified	Uncertain significance (May 20, 2024)
15-31483600-C-T		OTUD7A-related disorder	Benign (Jul 12, 2019)
15-31483642-C-G			Likely benign (Aug 01, 2022)
15-31483646-C-A		not specified	Uncertain significance (Jul 13, 2022)
15-31483730-T-TCGTCCCGCGCGCCC		OTUD7A-related disorder	Uncertain significance (Mar 30, 2023)
15-31483749-C-T		not specified	Uncertain significance (Nov 08, 2022)
15-31483779-G-A		not specified	Uncertain significance (Feb 11, 2022)
15-31483781-G-A		not specified	Uncertain significance (Dec 21, 2023)
15-31483788-G-A		not specified	Uncertain significance (Aug 12, 2021)
15-31483801-C-G		OTUD7A-related disorder	Benign (Jul 02, 2018)
15-31483809-C-T		not specified	Uncertain significance (May 18, 2023)
15-31483818-T-C		OTUD7A-related disorder	Benign (Jul 02, 2018)
15-31483829-G-A		not specified	Uncertain significance (Dec 28, 2023)
15-31483839-C-A		not specified	Uncertain significance (Oct 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTUD7A	protein_coding	protein_coding	ENST00000307050	11	387664

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.952	0.0475	125721	0	25	125746	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.87	284	456	0.623	0.0000305	5862
Missense in Polyphen		125	272.19	0.45924		3118
Synonymous	-0.572	224	213	1.05	0.0000165	1949
Loss of Function	4.39	5	31.6	0.158	0.00000152	396

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00105	0.00103
Finnish	0.000139	0.0000924
European (Non-Finnish)	0.0000193	0.0000176
Middle Eastern	0.00105	0.00103
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has deubiquitinating activity towards 'Lys-11'-linked polyubiquitin chains. {ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:23827681}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Ovarian tumor domain proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.0796
• rvis_EVS: -1.15
• rvis_percentile_EVS: 6.23

Haploinsufficiency Scores

• pHI: 0.242
• hipred: Y
• hipred_score: 0.809
• ghis: 0.606

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.102

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Otud7a
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• Biological process: protein deubiquitination;protein K11-linked deubiquitination;negative regulation of I-kappaB kinase/NF-kappaB signaling;protein K63-linked deubiquitination;protein K48-linked deubiquitination;protein deubiquitination involved in ubiquitin-dependent protein catabolic process
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: DNA binding;thiol-dependent ubiquitin-specific protease activity;zinc ion binding;thiol-dependent ubiquitinyl hydrolase activity;K63-linked polyubiquitin modification-dependent protein binding