USP18

ubiquitin specific peptidase 18, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 22:18149843-18177397

Links

ENSG00000184979 ∙ ∙ OMIM:607057 ∙ HGNC:12616 ∙ Uniprot:Q9UMW8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pseudo-TORCH syndrome 2 (Strong), mode of inheritance: AR
• pseudo-TORCH syndrome 2 (Strong), mode of inheritance: AR
• pseudo-TORCH syndrome 2 (Supportive), mode of inheritance: AR
• pseudo-TORCH syndrome 2 (Definitive), mode of inheritance: AR
• pseudo-TORCH syndrome 2 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pseudo-TORCH syndrome 2	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	Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	12833411; 27325888

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP18 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP18 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				5	1	6
missense			15	1	4	20
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				1	1	2
non coding					3	3
Total	0	2	15	6	8

Variants in USP18

This is a list of pathogenic ClinVar variants found in the USP18 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-18157533-G-A		not specified	Benign (Nov 12, 2023)
22-18157668-G-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
22-18157736-G-A			Benign (Dec 31, 2019)
22-18157743-A-G		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
22-18157760-G-A		USP18-related disorder	Likely benign (Jun 01, 2018)
22-18157776-G-A		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
22-18160167-T-G			Benign (Dec 31, 2019)
22-18160180-G-T		Inborn genetic diseases	Uncertain significance (Apr 06, 2024)
22-18160233-C-T			Likely benign (Jan 01, 2024)
22-18160234-G-A		not specified	Uncertain significance (Dec 01, 2023)
22-18161890-C-T		Inborn genetic diseases	Uncertain significance (Jun 16, 2022)
22-18167155-A-G		not specified	Benign (Jan 24, 2024)
22-18167327-T-C		Inborn genetic diseases	Uncertain significance (May 01, 2024)
22-18167915-C-T		not specified	Benign (Nov 12, 2023)
22-18167920-C-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2022)
22-18167943-C-T		Inborn genetic diseases	Likely benign (Jun 07, 2023)
22-18167944-G-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
22-18167944-G-C		Inborn genetic diseases	Likely benign (Apr 29, 2024)
22-18167962-A-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
22-18167963-G-A		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
22-18169849-C-T			Benign (Dec 11, 2018)
22-18169868-C-T		Pseudo-TORCH syndrome 2	Likely pathogenic (May 02, 2023)
22-18169888-C-G		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
22-18169928-C-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2021)
22-18170769-A-G		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP18	protein_coding	protein_coding	ENST00000215794	10	27499

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00150	0.993	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.841	158	191	0.829	0.0000102	2458
Missense in Polyphen		41	59.425	0.68995		854
Synonymous	-0.144	78	76.4	1.02	0.00000448	660
Loss of Function	2.41	8	19.5	0.411	9.77e-7	240

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000286	0.000275
Ashkenazi Jewish	0.000206	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000368	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.000103	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the regulation of inflammatory response to interferon type 1 (PubMed:27325888). Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms. {ECO:0000269|PubMed:27325888}.
• Disease: DISEASE: Pseudo-TORCH syndrome 2 (PTORCH2) [MIM:617397]: An autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. {ECO:0000269|PubMed:27325888}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cytokine Signaling in Immune system;Post-translational protein modification;Metabolism of proteins;Immune System;Ub-specific processing proteases;Deubiquitination;Regulation of IFNA signaling;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.519
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.26

Haploinsufficiency Scores

• pHI: 0.0664
• hipred: Y
• hipred_score: 0.519
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.921

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp18
• Phenotype: homeostasis/metabolism phenotype; cellular 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); hematopoietic system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: usp18
• Affected structure: pharyngeal arch cartilage
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein deubiquitination;regulation of protein stability;regulation of inflammatory response;regulation of type I interferon-mediated signaling pathway
• Cellular component: nucleus;cytosol
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;ISG15-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity