OTUD4

OTU deubiquitinase 4, the group of OTU domain containing

Basic information

Region (hg38): 4:145110837-145180589

Links

ENSG00000164164 ∙ NCBI:54726 ∙ OMIM:611744 ∙ HGNC:24949 ∙ Uniprot:Q01804 ∙ 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 OTUD4 gene.

• Inborn genetic diseases (29 variants)
• not provided (4 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTUD4 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		3
missense			29			29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	29	3	0

Variants in OTUD4

This is a list of pathogenic ClinVar variants found in the OTUD4 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-145111042-G-A		not specified	Uncertain significance (Feb 22, 2023)
4-145111062-T-G		Malignant tumor of prostate	Uncertain significance (-)
4-145112254-G-A			Benign (Apr 04, 2018)
4-145119934-A-G		not specified	Uncertain significance (Jun 06, 2023)
4-145120042-A-T		not specified	Uncertain significance (Aug 13, 2021)
4-145123265-C-T			Benign (Apr 04, 2018)
4-145123482-A-G		not specified	Uncertain significance (Dec 22, 2023)
4-145137460-C-T		not specified	Uncertain significance (Jan 03, 2022)
4-145137534-G-A		not specified	Uncertain significance (Oct 20, 2023)
4-145137569-C-T		not specified	Uncertain significance (Dec 08, 2023)
4-145137683-G-C		not specified	Uncertain significance (Dec 28, 2023)
4-145137717-T-C		not specified	Uncertain significance (Dec 01, 2022)
4-145137745-G-A			Likely benign (Sep 01, 2022)
4-145137772-A-T		not specified	Conflicting classifications of pathogenicity (Jul 01, 2023)
4-145137776-G-A		not specified	Uncertain significance (Oct 04, 2022)
4-145137776-G-T		not specified	Uncertain significance (Feb 06, 2024)
4-145137782-G-C		Amenorrhea	Uncertain significance (Mar 08, 2021)
4-145137899-C-T		not specified	Uncertain significance (Apr 28, 2023)
4-145137960-G-T		not specified	Uncertain significance (Nov 18, 2022)
4-145137969-G-A		not specified	Uncertain significance (Oct 20, 2021)
4-145138037-G-A		not specified	Uncertain significance (Aug 10, 2021)
4-145138068-A-C		not specified	Uncertain significance (Sep 23, 2023)
4-145138126-G-C			Likely benign (Mar 01, 2023)
4-145138241-T-C		not specified	Uncertain significance (Nov 30, 2022)
4-145138258-C-A		not specified	Uncertain significance (Nov 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTUD4	protein_coding	protein_coding	ENST00000454497	20	69324

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000291	125724	0	23	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	434	536	0.810	0.0000262	6814
Missense in Polyphen		113	162.66	0.6947		2171
Synonymous	-0.0115	189	189	1.00	0.00000922	2021
Loss of Function	6.19	6	55.9	0.107	0.00000308	690

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000376	0.000376
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}.

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.381
• rvis_EVS: -0.99
• rvis_percentile_EVS: 8.56

Haploinsufficiency Scores

• pHI: 0.462
• hipred: Y
• hipred_score: 0.501
• ghis: 0.586

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Otud4

Zebrafish Information Network

• Gene name: otud4
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: protein deubiquitination;negative regulation of toll-like receptor signaling pathway;innate immune response;protein K63-linked deubiquitination;protein K48-linked deubiquitination;positive regulation of DNA demethylation;regulation of protein K48-linked deubiquitination;negative regulation of interleukin-1-mediated signaling pathway
• Cellular component: nucleus;cytoplasm
• Molecular function: RNA binding;thiol-dependent ubiquitin-specific protease activity;protein binding;protein-containing complex scaffold activity;Lys63-specific deubiquitinase activity