USP13

ubiquitin specific peptidase 13, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 3:179653031-179804366

Links

ENSG00000058056 ∙ NCBI:8975 ∙ OMIM:603591 ∙ HGNC:12611 ∙ Uniprot:Q92995 ∙ 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 USP13 gene.

• Inborn genetic diseases (34 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP13 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			32			32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			2			2
Total	0	0	34	0	2

Variants in USP13

This is a list of pathogenic ClinVar variants found in the USP13 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-179653236-G-A		not specified	Uncertain significance (Oct 06, 2021)
3-179653241-G-T		not specified	Uncertain significance (Jan 18, 2022)
3-179653266-G-A		not specified	Uncertain significance (Feb 17, 2022)
3-179653286-G-A		not specified	Uncertain significance (Nov 02, 2023)
3-179653305-T-G		not specified	Uncertain significance (Jun 24, 2022)
3-179653385-G-A		not specified	Uncertain significance (Feb 23, 2023)
3-179681888-G-A		not specified	Uncertain significance (Feb 27, 2023)
3-179701028-T-G		not specified	Uncertain significance (Feb 15, 2023)
3-179707000-T-C		not specified	Uncertain significance (Dec 20, 2021)
3-179708780-A-G		not specified	Uncertain significance (Feb 23, 2023)
3-179708794-C-T			Benign (Jul 13, 2018)
3-179708868-C-T		not specified	Uncertain significance (Jan 08, 2024)
3-179708873-G-T		not specified	Uncertain significance (Mar 04, 2024)
3-179708893-G-T		not specified	Uncertain significance (Feb 16, 2023)
3-179719946-A-T		not specified	Uncertain significance (Dec 13, 2022)
3-179720018-T-C		not specified	Uncertain significance (Nov 22, 2023)
3-179721405-G-A		not specified	Uncertain significance (Apr 21, 2022)
3-179721460-T-C		not specified	Uncertain significance (Jul 12, 2023)
3-179721472-G-A		not specified	Uncertain significance (Dec 19, 2022)
3-179721553-T-C		not specified	Uncertain significance (Feb 12, 2024)
3-179730689-G-A		not specified	Uncertain significance (Jan 05, 2022)
3-179740271-C-T		not specified	Uncertain significance (Jan 26, 2022)
3-179740305-C-T		not specified	Uncertain significance (Dec 27, 2023)
3-179740323-G-A		not specified	Uncertain significance (Mar 20, 2023)
3-179742275-C-T		not specified	Uncertain significance (Jun 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP13	protein_coding	protein_coding	ENST00000263966	21	136647

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.07e-12	0.999	125665	0	83	125748	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.90	376	495	0.760	0.0000266	5709
Missense in Polyphen		110	153.24	0.71781		1807
Synonymous	0.751	173	186	0.930	0.0000110	1600
Loss of Function	2.99	27	49.7	0.543	0.00000282	553

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000586	0.000583
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000221	0.000217
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000361	0.000360
Middle Eastern	0.000221	0.000217
South Asian	0.000261	0.000261
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum- associated degradation (ERAD). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34- containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data. {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410}.
• Pathway: Signal Transduction;Regulation of PTEN stability and activity;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;PTEN Regulation;PIP3 activates AKT signaling;Deubiquitination;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.769
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.04

Haploinsufficiency Scores

• pHI: 0.233
• hipred: Y
• hipred_score: 0.747
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp13

Zebrafish Information Network

• Gene name: usp13
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: regulation of transcription, DNA-templated;ubiquitin-dependent protein catabolic process;autophagy;cell population proliferation;regulation of autophagy;protein deubiquitination;melanocyte differentiation;protein K29-linked deubiquitination;protein K6-linked deubiquitination;protein stabilization;protein K63-linked deubiquitination;positive regulation of ERAD pathway;maintenance of unfolded protein involved in ERAD pathway
• Cellular component: nucleoplasm;cytosol
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;zinc ion binding;ubiquitin protein ligase binding;thiol-dependent ubiquitinyl hydrolase activity;ubiquitin binding;ubiquitin-like protein ligase binding;chaperone binding;proteasome binding;BAT3 complex binding;ubiquitin-specific protease activity involved in positive regulation of ERAD pathway