OTUB1

OTU deubiquitinase, ubiquitin aldehyde binding 1, the group of OTU domain containing

Basic information

Region (hg38): 11:63985853-64001811

Links

ENSG00000167770 ∙ NCBI:55611 ∙ OMIM:608337 ∙ HGNC:23077 ∙ Uniprot:Q96FW1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OTUB1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTUB1 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						0
missense			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	8	0	0

Variants in OTUB1

This is a list of pathogenic ClinVar variants found in the OTUB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-63986485-A-G		not specified	Uncertain significance (Mar 26, 2024)
11-63988355-A-C		not specified	Uncertain significance (Feb 10, 2022)
11-63988355-A-G		not specified	Uncertain significance (Oct 22, 2021)
11-63988732-A-G		not specified	Uncertain significance (Jan 04, 2024)
11-63996549-C-T		not specified	Uncertain significance (Dec 07, 2023)
11-63996647-C-T		not specified	Uncertain significance (Nov 09, 2021)
11-63996868-T-C		not specified	Uncertain significance (Nov 10, 2022)
11-63997189-A-G		not specified	Uncertain significance (Nov 09, 2021)
11-63997414-C-A		not specified	Uncertain significance (Jan 04, 2022)
11-63998961-G-A		not specified	Uncertain significance (Feb 15, 2023)
11-63998968-G-A			Likely benign (Apr 01, 2022)
11-63998972-G-A		not specified	Uncertain significance (Jun 02, 2024)
11-63998997-C-T		not specified	Uncertain significance (Aug 30, 2021)
11-63999021-T-C		not specified	Uncertain significance (Jan 26, 2022)
11-63999371-A-G		not specified	Uncertain significance (May 01, 2024)
11-63999378-T-C		not specified	Likely benign (May 14, 2024)
11-63999533-A-C		not specified	Uncertain significance (Oct 12, 2021)
11-63999550-C-A		not specified	Uncertain significance (Mar 15, 2024)
11-63999559-G-A		not specified	Uncertain significance (Jan 26, 2022)
11-63999650-G-A		not specified	Uncertain significance (Feb 07, 2023)
11-63999688-T-G		not specified	Uncertain significance (Jan 31, 2024)
11-63999694-C-T		not specified	Uncertain significance (Jul 15, 2021)
11-63999755-G-A		not specified	Uncertain significance (Apr 28, 2023)
11-64000297-C-G		not specified	Uncertain significance (Oct 05, 2023)
11-64000337-C-T		not specified	Uncertain significance (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTUB1	protein_coding	protein_coding	ENST00000538426	7	15959

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.971	0.0289	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.19	85	164	0.518	0.0000103	1780
Missense in Polyphen		13	59.907	0.217		644
Synonymous	-0.384	74	69.9	1.06	0.00000475	497
Loss of Function	3.39	1	15.4	0.0651	7.39e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys- 48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.
• Pathway: Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Ovarian tumor domain proteases;Deubiquitination (Consensus)

Intolerance Scores

• loftool: 0.244
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.104
• hipred: Y
• hipred_score: 0.675
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Otub1
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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)

Zebrafish Information Network

• Gene name: otub1a
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: adaptive immune response;DNA repair;cellular response to DNA damage stimulus;protein deubiquitination;protein K48-linked deubiquitination;cellular response to interleukin-1;negative regulation of histone H2A K63-linked ubiquitination;negative regulation of double-strand break repair
• Cellular component: nucleus;nucleoplasm;cytosol;extracellular exosome
• Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;NEDD8-specific protease activity;ubiquitin protein ligase binding;ubiquitin binding