USP5

ubiquitin specific peptidase 5, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 12:6852148-6866632

Links

ENSG00000111667 ∙ ∙ OMIM:601447 ∙ HGNC:12628 ∙ Uniprot:P45974 ∙ 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 USP5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP5 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				1	5	6
missense			28	1		29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	28	2	5

Variants in USP5

This is a list of pathogenic ClinVar variants found in the USP5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-6852190-T-C		not specified	Uncertain significance (Jan 26, 2022)
12-6852233-C-T			Benign (May 10, 2018)
12-6852239-G-A			Likely benign (Sep 01, 2022)
12-6855481-G-T		not specified	Uncertain significance (Nov 03, 2022)
12-6855492-G-A		not specified	Uncertain significance (Sep 20, 2024)
12-6855509-C-T		not specified	Uncertain significance (Oct 21, 2024)
12-6855512-C-T		not specified	Uncertain significance (May 20, 2024)
12-6855525-C-T		not specified	Likely benign (Nov 30, 2021)
12-6855778-C-T			Benign (May 10, 2018)
12-6855794-C-G		not specified	Uncertain significance (Aug 08, 2022)
12-6855795-G-A		not specified	Uncertain significance (Apr 13, 2023)
12-6856028-G-A		not specified	Uncertain significance (Sep 22, 2023)
12-6856063-C-A		not specified	Uncertain significance (Mar 20, 2024)
12-6856134-A-C		not specified	Uncertain significance (Dec 04, 2024)
12-6856386-C-T		not specified	Uncertain significance (Jan 24, 2024)
12-6856420-A-G		not specified	Uncertain significance (Nov 24, 2024)
12-6858517-C-A		not specified	Uncertain significance (Mar 24, 2023)
12-6860158-C-T			Benign (Apr 04, 2018)
12-6860186-A-G		not specified	Uncertain significance (Aug 07, 2024)
12-6860200-C-A		not specified	Uncertain significance (Nov 10, 2022)
12-6860201-C-T		not specified	Uncertain significance (Jul 12, 2022)
12-6860439-A-G		not specified	Uncertain significance (Feb 28, 2024)
12-6861073-C-T			Benign (Apr 04, 2018)
12-6861091-G-A		not specified	Uncertain significance (Dec 12, 2023)
12-6861469-A-C		not specified	Uncertain significance (Dec 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP5	protein_coding	protein_coding	ENST00000229268	20	14505

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.964	0.0360	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.36	310	527	0.588	0.0000315	5621
Missense in Polyphen		83	184.75	0.44927		2024
Synonymous	-0.470	219	210	1.04	0.0000130	1661
Loss of Function	5.16	8	45.6	0.175	0.00000236	522

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000114	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000114	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys- 63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition. {ECO:0000269|PubMed:19098288}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Synthesis of active ubiquitin: roles of E1 and E2 enzymes;Ub-specific processing proteases;Deubiquitination;Protein ubiquitination (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.358
• rvis_EVS: -1.68
• rvis_percentile_EVS: 2.63

Haploinsufficiency Scores

• pHI: 0.690
• hipred: Y
• hipred_score: 0.800
• ghis: 0.534

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp5
• Phenotype: hematopoietic system 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); immune system phenotype

Zebrafish Information Network

• Gene name: usp5
• Affected structure: caudal fin upper lobe
• Phenotype tag: abnormal
• Phenotype quality: fused with

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein deubiquitination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;protein K48-linked deubiquitination
• Cellular component: lysosome;cytosol
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;zinc ion binding;thiol-dependent ubiquitinyl hydrolase activity;ubiquitin binding