USP2

ubiquitin specific peptidase 2, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 11:119355215-119381711

Links

ENSG00000036672 ∙ NCBI:9099 ∙ OMIM:604725 ∙ HGNC:12618 ∙ Uniprot:O75604 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP2 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					2	2
missense			35	3	1	39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	35	3	3

Variants in USP2

This is a list of pathogenic ClinVar variants found in the USP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-119356842-C-G		not specified	Uncertain significance (May 17, 2023)
11-119356918-T-C		not specified	Uncertain significance (May 09, 2024)
11-119356921-C-T		not specified	Uncertain significance (Dec 28, 2022)
11-119357188-T-C		not specified	Uncertain significance (Jul 12, 2023)
11-119357197-T-G		not specified	Uncertain significance (Nov 19, 2022)
11-119357206-G-A		not specified	Uncertain significance (Oct 26, 2022)
11-119357255-C-G		not specified	Uncertain significance (Dec 26, 2023)
11-119357286-T-A		not specified	Uncertain significance (Jun 11, 2021)
11-119357489-T-C		not specified	Uncertain significance (Jan 16, 2024)
11-119357807-C-T		not specified	Uncertain significance (May 26, 2024)
11-119358037-T-C		not specified	Uncertain significance (Sep 22, 2023)
11-119358156-A-C		not specified	Uncertain significance (Feb 06, 2024)
11-119358794-G-A		not specified	Uncertain significance (Aug 12, 2021)
11-119358820-C-T		not specified	Uncertain significance (Nov 21, 2022)
11-119359072-C-T		not specified	Uncertain significance (Nov 18, 2022)
11-119359082-C-T		not specified	Uncertain significance (Aug 09, 2021)
11-119359249-G-A		not specified	Uncertain significance (Feb 28, 2023)
11-119359250-G-A		not specified	Uncertain significance (Feb 06, 2023)
11-119359334-T-C		not specified	Uncertain significance (Jul 26, 2022)
11-119359543-C-T		not specified	Likely benign (Nov 17, 2022)
11-119360215-C-G		not specified	Uncertain significance (Dec 06, 2022)
11-119372712-C-T		not specified	Likely benign (Dec 19, 2022)
11-119372735-C-T		not specified	Uncertain significance (Dec 17, 2023)
11-119372777-G-A		not specified	Uncertain significance (Mar 05, 2024)
11-119372792-G-A			Benign (May 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP2	protein_coding	protein_coding	ENST00000260187	12	26512

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000691	0.999	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	306	372	0.822	0.0000237	3883
Missense in Polyphen		73	116.2	0.62824		1292
Synonymous	-0.112	149	147	1.01	0.00000861	1241
Loss of Function	3.60	12	35.0	0.343	0.00000238	343

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000606	0.000604
Ashkenazi Jewish	0.000106	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.000103	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19917254, PubMed:19838211). Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211). Has no deubiquitinase activity against p53/TP53 (PubMed:17290220). Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1 (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity). {ECO:0000250|UniProtKB:O88623, ECO:0000250|UniProtKB:Q5U349, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:19917254}.
• Pathway: Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;TNFR1-induced NFkappaB signaling pathway;TNFR1-induced proapoptotic signaling;TNF signaling;Ub-specific processing proteases;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;Deubiquitination;Death Receptor Signalling;Regulation of TP53 Activity;Transcriptional Regulation by TP53;TNFalpha (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.735
• rvis_EVS: 0.07
• rvis_percentile_EVS: 59.04

Haploinsufficiency Scores

• pHI: 0.472
• hipred: Y
• hipred_score: 0.790
• ghis: 0.609

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.743

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp2
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;ubiquitin-dependent protein catabolic process;cell cycle;muscle organ development;protein deubiquitination;circadian regulation of gene expression;entrainment of circadian clock by photoperiod;locomotor rhythm;positive regulation of mitotic cell cycle;circadian behavior;protein stabilization
• Cellular component: nucleoplasm;cytoplasm;centrosome;membrane;perinuclear region of cytoplasm
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;cyclin binding;ubiquitin protein ligase binding;thiol-dependent ubiquitinyl hydrolase activity;identical protein binding;metal ion binding