OTUD5

OTU deubiquitinase 5, the group of OTU domain containing

Basic information

Region (hg38): X:48922024-48958386

Links

ENSG00000068308

∙ NCBI:55593 ∙ OMIM:300713 ∙ HGNC:25402 ∙ Uniprot:Q96G74 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

multiple congenital anomalies/dysmorphic syndrome (Moderate), mode of inheritance: XL
multiple congenital anomalies-neurodevelopmental syndrome, X-linked (Strong), mode of inheritance: XL
multiple congenital anomalies-neurodevelopmental syndrome, X-linked (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple congenital anomalies-neurodevelopmental syndrome, X-linked	XL	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal	33131077; 33523931

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OTUD5 gene.

not_provided (30 variants)
Inborn_genetic_diseases (30 variants)
Multiple_congenital_anomalies-neurodevelopmental_syndrome,_X-linked (18 variants)
OTUD5-related_disorder (7 variants)
not_specified (2 variants)
Dysplastic_corpus_callosum (1 variants)
Neurodegeneration_with_brain_iron_accumulation_5 (1 variants)
See_cases (1 variants)
Ependymoma (1 variants)
Abnormal_cerebral_cortex_morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTUD5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001136157.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar	1 clinvar	10
missense	4 clinvar	3 clinvar	54 clinvar	3 clinvar		64
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	5	3	55	12	1

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OTUD5	protein_coding	protein_coding	ENST00000156084	9	36344

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00283	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.99	44	205	0.215	0.0000164	3643
Missense in Polyphen		3	60.517	0.049573		961
Synonymous	0.0542	79	79.6	0.992	0.00000624	1188
Loss of Function	3.85	0	17.2	0.00	0.00000132	262

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: Deubiquitinating enzyme that functions as negative regulator of the innate immune system. Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production. Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'- linked ubiquitin chains (in vitro). {ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:22245969, ECO:0000269|PubMed:23827681}.;
Pathway: RIG-I-like receptor signaling pathway - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Gastric Cancer Network 2;RIG-I-like Receptor Signaling;Post-translational protein modification;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Metabolism of proteins;Innate Immune System;Immune System;Negative regulators of DDX58/IFIH1 signaling;Ovarian tumor domain proteases;Deubiquitination (Consensus)

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool
rvis_EVS: -0.16
rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

pHI: 0.368
hipred: Y
hipred_score: 0.831
ghis: 0.513

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.772

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Otud5
Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; 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); hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype; embryo phenotype;

Zebrafish Information Network

Gene name: otud5b
Affected structure: trunk
Phenotype tag: abnormal
Phenotype quality: bent

Gene ontology

Biological process: protein deubiquitination;negative regulation of type I interferon production;response to lipopolysaccharide;protein K63-linked deubiquitination;protein K48-linked deubiquitination
Cellular component: cytosol
Molecular function: thiol-dependent ubiquitin-specific protease activity;Lys63-specific deubiquitinase activity;ubiquitinyl hydrolase activity;Lys48-specific deubiquitinase activity