USP15

ubiquitin specific peptidase 15, the group of Ubiquitin specific peptidases|MicroRNA protein coding host genes

Basic information

Region (hg38): 12:62260338-62417431

Links

ENSG00000135655 ∙ NCBI:9958 ∙ OMIM:604731 ∙ HGNC:12613 ∙ Uniprot:Q9Y4E8 ∙ 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 USP15 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP15 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				4	3	7
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	4	3

Variants in USP15

This is a list of pathogenic ClinVar variants found in the USP15 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-62294276-G-A		not specified	Uncertain significance (Jul 13, 2022)
12-62302792-G-A		not specified	Uncertain significance (Apr 15, 2024)
12-62302818-C-T		USP15-related disorder	Benign (Oct 17, 2019)
12-62321487-A-G		not specified	Uncertain significance (Oct 06, 2021)
12-62325901-T-A		not specified	Uncertain significance (Oct 20, 2023)
12-62325923-T-C		not specified	Uncertain significance (Dec 08, 2021)
12-62355361-A-G		USP15-related disorder	Likely benign (Mar 05, 2019)
12-62355413-C-G		not specified	Uncertain significance (Mar 07, 2023)
12-62381643-G-A		not specified	Uncertain significance (Feb 23, 2023)
12-62383843-C-G		not specified	Uncertain significance (Dec 16, 2023)
12-62384120-G-T		not specified	Uncertain significance (Feb 10, 2023)
12-62384139-T-C		USP15-related disorder • not specified	Uncertain significance (Oct 12, 2021)
12-62384200-A-G		USP15-related disorder	Likely benign (Jun 18, 2019)
12-62384284-A-G		USP15-related disorder	Benign (Oct 17, 2019)
12-62389463-A-G		USP15-related disorder	Uncertain significance (Sep 17, 2023)
12-62389469-T-A		not specified	Uncertain significance (May 26, 2022)
12-62389609-T-C		not specified	Uncertain significance (Jun 26, 2023)
12-62389619-T-C		USP15-related disorder	Likely benign (Jul 18, 2019)
12-62389649-C-T		USP15-related disorder	Likely benign (Nov 08, 2019)
12-62389709-A-G		USP15-related disorder	Likely benign (Apr 13, 2024)
12-62389837-G-A		not specified	Uncertain significance (Sep 27, 2022)
12-62390871-G-A		not specified	Uncertain significance (Nov 08, 2022)
12-62390920-G-T		not specified	Uncertain significance (Sep 16, 2021)
12-62390941-G-A		not specified	Uncertain significance (Jan 24, 2023)
12-62390958-A-T		not specified	Uncertain significance (May 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP15	protein_coding	protein_coding	ENST00000280377	22	157093

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000267	125709	0	8	125717	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.50	275	494	0.557	0.0000237	6535
Missense in Polyphen		48	144.91	0.33124		1886
Synonymous	1.24	152	173	0.880	0.00000852	1711
Loss of Function	6.20	6	56.2	0.107	0.00000316	703

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000590	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000538	0.0000528
Middle Eastern	0.0000590	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF- beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys- 48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF- kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). {ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689, ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102}.
• Pathway: Mitophagy - animal - Homo sapiens (human);Signal Transduction;Post-translational protein modification;Metabolism of proteins;UCH proteinases;Ub-specific processing proteases;Deubiquitination;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.482
• rvis_EVS: -0.98
• rvis_percentile_EVS: 8.75

Haploinsufficiency Scores

• pHI: 0.805
• hipred: Y
• hipred_score: 0.704
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp15
• 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); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;transforming growth factor beta receptor signaling pathway;protein deubiquitination;BMP signaling pathway;monoubiquitinated protein deubiquitination;histone H2B conserved C-terminal lysine deubiquitination;pathway-restricted SMAD protein phosphorylation
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;transforming growth factor beta receptor binding;protein binding;thiol-dependent ubiquitinyl hydrolase activity;identical protein binding;SMAD binding;ubiquitin modification-dependent histone binding