USP33

ubiquitin specific peptidase 33, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 1:77695987-77759852

Links

ENSG00000077254 ∙ NCBI:23032 ∙ OMIM:615146 ∙ HGNC:20059 ∙ Uniprot:Q8TEY7 ∙ 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 USP33 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP33 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			54			54
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	54	0	0

Variants in USP33

This is a list of pathogenic ClinVar variants found in the USP33 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-77697387-G-A		not specified	Uncertain significance (Apr 09, 2024)
1-77697404-T-A		not specified	Uncertain significance (May 24, 2024)
1-77697454-A-C		not specified	Uncertain significance (Dec 28, 2022)
1-77697867-C-G		not specified	Uncertain significance (Aug 28, 2024)
1-77697904-T-C		not specified	Uncertain significance (Feb 14, 2024)
1-77697919-G-T		not specified	Uncertain significance (Dec 07, 2024)
1-77701401-T-C		not specified	Uncertain significance (Jun 16, 2024)
1-77701435-T-C		not specified	Uncertain significance (Oct 01, 2024)
1-77701437-G-C		not specified	Uncertain significance (Dec 19, 2022)
1-77701461-G-A		not specified	Uncertain significance (May 26, 2024)
1-77701462-C-T		not specified	Uncertain significance (Feb 15, 2023)
1-77714662-C-T		not specified	Uncertain significance (Jan 22, 2024)
1-77714669-C-G		not specified	Uncertain significance (May 31, 2023)
1-77714740-T-G		not specified	Uncertain significance (Oct 30, 2023)
1-77714756-C-G		not specified	Uncertain significance (Apr 26, 2023)
1-77714760-T-C		not specified	Uncertain significance (Sep 11, 2024)
1-77715846-G-C		not specified	Uncertain significance (Apr 30, 2024)
1-77717909-A-G		not specified	Uncertain significance (Mar 25, 2024)
1-77717963-C-T		not specified	Uncertain significance (Dec 14, 2021)
1-77717971-G-A			Uncertain significance (Nov 01, 2022)
1-77718038-T-G		not specified	Uncertain significance (Dec 05, 2024)
1-77722040-T-C		not specified	Uncertain significance (Oct 06, 2021)
1-77722076-C-T		not specified	Uncertain significance (Dec 19, 2022)
1-77722100-T-C		not specified	Uncertain significance (Feb 10, 2022)
1-77722154-T-G		not specified	Uncertain significance (Apr 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP33	protein_coding	protein_coding	ENST00000370793	24	63866

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.862	0.138	125725	0	20	125745	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.10	341	469	0.727	0.0000225	6223
Missense in Polyphen		99	195.68	0.50593		2649
Synonymous	-0.425	168	161	1.04	0.00000840	1686
Loss of Function	5.50	11	55.0	0.200	0.00000285	685

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000605	0.0000605
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000709	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.000177	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta- arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. {ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:23486064}.
• Pathway: Developmental Biology;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.541
• rvis_EVS: -1.44
• rvis_percentile_EVS: 3.96

Haploinsufficiency Scores

• pHI: 0.713
• hipred: Y
• hipred_score: 0.639
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.758

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp33
• Phenotype: hematopoietic system phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: usp33
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;endocytosis;axon guidance;regulation of G protein-coupled receptor signaling pathway;cellular response to starvation;regulation of autophagy;cell migration;protein deubiquitination;negative regulation of protein binding;positive regulation of protein binding;protein stabilization;centrosome duplication;protein K63-linked deubiquitination;protein K48-linked deubiquitination
• Cellular component: nucleoplasm;cytoplasm;Golgi apparatus;centrosome;cytosol;focal adhesion;VCB complex;cell body;perinuclear region of cytoplasm
• Molecular function: G protein-coupled receptor binding;cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;zinc ion binding;Ral GTPase binding;thiol-dependent ubiquitinyl hydrolase activity;ubiquitin binding