OTUD6B

OTU deubiquitinase 6B, the group of OTU domain containing

Basic information

Region (hg38): 8:91070195-91087095

Links

ENSG00000155100 ∙ NCBI:51633 ∙ OMIM:612021 ∙ HGNC:24281 ∙ Uniprot:Q8N6M0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (IDDFSDA)	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	Craniofacial; Musculoskeletal; Neurologic	28343629

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OTUD6B gene.

• not provided (29 variants)
• Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (22 variants)
• Inborn genetic diseases (15 variants)
• Intellectual disability;Epilepsy;Dysmorphic features (3 variants)
• not specified (2 variants)
• OTUD6B-related condition (2 variants)
• Epilepsy;Dysmorphic features;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTUD6B 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				3	1	4
missense		3	20			23
nonsense	3	2	1			6
start loss						0
frameshift	4	2	1			7
inframe indel						0
splice donor/acceptor (+/-2bp)	2					2
splice region			1	3		4
non coding			1		1	2
Total	9	7	23	3	2

Highest pathogenic variant AF is 0.000145

Variants in OTUD6B

This is a list of pathogenic ClinVar variants found in the OTUD6B region.

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

Position	Type	Phenotype	Significance	ClinVar
8-91070310-A-G			Uncertain significance (Jun 28, 2019)
8-91070335-C-T		Inborn genetic diseases	Uncertain significance (Jan 10, 2022)
8-91070346-A-G		Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies • not specified • OTUD6B-related disorder	Conflicting classifications of pathogenicity (Apr 25, 2023)
8-91070370-G-A		Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	Uncertain significance (Mar 03, 2018)
8-91070382-G-A		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
8-91070399-G-C		OTUD6B-related disorder	Uncertain significance (Oct 23, 2023)
8-91070403-G-T			Pathogenic (Nov 27, 2021)
8-91070409-C-G			Uncertain significance (Nov 02, 2021)
8-91070427-C-G		OTUD6B-related disorder	Uncertain significance (Mar 20, 2023)
8-91070465-A-G			Likely benign (Mar 01, 2022)
8-91071136-A-G		Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies • Intellectual disability;Epilepsy;Dysmorphic features	Pathogenic (Jan 09, 2017)
8-91071151-C-G			Likely benign (Oct 01, 2023)
8-91071158-A-T		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
8-91071167-C-G		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
8-91071186-G-A		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
8-91071196-A-G		Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	Benign (Sep 05, 2021)
8-91071200-A-G		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
8-91071227-G-A		Inborn genetic diseases	Uncertain significance (Oct 29, 2020)
8-91071242-CAT-C		Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	Pathogenic (Nov 07, 2019)
8-91071244-TAGAG-T		Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	Pathogenic/Likely pathogenic (Jul 30, 2023)
8-91071247-A-G		OTUD6B-related disorder	Likely benign (Jan 27, 2020)
8-91071260-C-T			Likely pathogenic (Mar 03, 2021)
8-91073851-C-G		OTUD6B-related disorder	Uncertain significance (Oct 23, 2023)
8-91073886-G-A		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
8-91073911-G-T			Uncertain significance (Feb 01, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTUD6B	protein_coding	protein_coding	ENST00000285420	7	16900

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-7	0.371	125523	0	70	125593	0.000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.296	145	155	0.933	0.00000738	2084
Missense in Polyphen		53	61.541	0.86121		858
Synonymous	-0.0496	55	54.5	1.01	0.00000257	576
Loss of Function	0.650	12	14.7	0.817	6.91e-7	218

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00112
Ashkenazi Jewish	0.000104	0.0000993
East Asian	0.000550	0.000544
Finnish	0.0000927	0.0000925
European (Non-Finnish)	0.000156	0.000150
Middle Eastern	0.000550	0.000544
South Asian	0.000137	0.000131
Other	0.000766	0.000653

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1 (PubMed:21267069, PubMed:27864334). May associate with the protein synthesis initiation complex and modify its ubiquitination to repress translation (PubMed:27864334). May also repress DNA synthesis and modify different cellular targets thereby regulating cell growth and proliferation (PubMed:27864334). May also play a role in proteasome assembly and function (PubMed:28343629). {ECO:0000269|PubMed:21267069, ECO:0000269|PubMed:27864334, ECO:0000269|PubMed:28343629}.
• Disease: DISEASE: Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (IDDFSDA) [MIM:617452]: An autosomal recessive severe multisystem disorder characterized by poor overall growth, developmental delay, early- onset seizures, intellectual disability, and dysmorphic features. Additional features include microcephaly, absent speech, hypotonia, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features. {ECO:0000269|PubMed:28343629}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: EGFR1 (Consensus)

Recessive Scores

• pRec: 0.0953

Intolerance Scores

• loftool: 0.587
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.53

Haploinsufficiency Scores

• pHI: 0.0869
• hipred: N
• hipred_score: 0.170
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.574

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Otud6b
• Phenotype: growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: cell population proliferation;protein deubiquitination;proteasome assembly
• Cellular component: eukaryotic translation initiation factor 4F complex
• Molecular function: thiol-dependent ubiquitin-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity