USP10

ubiquitin specific peptidase 10, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 16:84699986-84779922

Links

ENSG00000103194

∙ NCBI:9100 ∙ OMIM:609818 ∙ HGNC:12608 ∙ Uniprot:Q14694 ∙ 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 USP10 gene.

not_specified (132 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP10 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005153.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			125 clinvar	7 clinvar		132
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	125	7	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP10	protein_coding	protein_coding	ENST00000219473	14	79945

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00589	124298	0	345	124643	0.00138

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.674	494	454	1.09	0.0000256	5158
Missense in Polyphen		116	162.09	0.71565		1942
Synonymous	-2.29	227	187	1.21	0.0000121	1611
Loss of Function	4.90	5	37.3	0.134	0.00000205	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000374	0.000352
Ashkenazi Jewish	0.00200	0.00189
East Asian	0.0175	0.0168
Finnish	0.00	0.00
European (Non-Finnish)	0.000120	0.0000973
Middle Eastern	0.0175	0.0168
South Asian	0.000249	0.000229
Other	0.000352	0.000330

dbNSFP

Source: dbNSFP

Function: FUNCTION: Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. 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. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989}.;
Pathway: DNA Repair;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass (Consensus)

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool: 0.523
rvis_EVS: -0.24
rvis_percentile_EVS: 36.31

Haploinsufficiency Scores

pHI: 0.697
hipred: Y
hipred_score: 0.783
ghis: 0.553

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.501

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Usp10
Phenotype: cellular 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);

Zebrafish Information Network

Gene name: usp10
Affected structure: post-vent region
Phenotype tag: abnormal
Phenotype quality: curled

Gene ontology

Biological process: ubiquitin-dependent protein catabolic process;autophagy;cellular response to DNA damage stimulus;regulation of autophagy;protein deubiquitination;translesion synthesis;DNA damage response, signal transduction by p53 class mediator;negative regulation of I-kappaB kinase/NF-kappaB signaling;cellular response to interleukin-1
Cellular component: nucleus;nucleoplasm;cytoplasm;early endosome;cytosol;protein-containing complex
Molecular function: p53 binding;RNA binding;cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;thiol-dependent ubiquitinyl hydrolase activity;ion channel binding