USP30

ubiquitin specific peptidase 30, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 12:109023088-109088023

Links

ENSG00000135093 ∙ NCBI:84749 ∙ OMIM:612492 ∙ HGNC:20065 ∙ Uniprot:Q70CQ3 ∙ 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 USP30 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP30 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			25	1		26
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	26	1	0

Variants in USP30

This is a list of pathogenic ClinVar variants found in the USP30 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-109052692-G-A		not specified	Uncertain significance (Oct 19, 2021)
12-109052708-G-A		not specified	Uncertain significance (Apr 27, 2023)
12-109052713-C-T		not specified	Uncertain significance (Nov 09, 2021)
12-109052752-C-A		not specified	Uncertain significance (Oct 27, 2022)
12-109057926-G-A		not specified	Uncertain significance (Nov 22, 2021)
12-109058040-A-T		not specified	Uncertain significance (Dec 14, 2021)
12-109058073-A-C		not specified	Uncertain significance (Nov 01, 2022)
12-109067525-C-A			Benign (Apr 06, 2018)
12-109071631-A-T		not specified	Uncertain significance (Jun 21, 2023)
12-109072336-C-T		not specified	Uncertain significance (Mar 30, 2024)
12-109072345-C-A		not specified	Uncertain significance (Dec 03, 2021)
12-109073506-A-G		not specified	Uncertain significance (Dec 28, 2023)
12-109073531-A-G		not specified	Uncertain significance (Dec 21, 2022)
12-109082853-GTC-G			Uncertain significance (Jan 30, 2020)
12-109082874-G-A		not specified	Uncertain significance (Jan 06, 2023)
12-109082898-C-T		not specified	Uncertain significance (Nov 15, 2021)
12-109082930-A-G		not specified	Uncertain significance (Sep 26, 2023)
12-109083059-C-T		not specified	Likely benign (Feb 26, 2024)
12-109084973-C-T		not specified	Uncertain significance (Oct 13, 2023)
12-109085024-A-G		not specified	Uncertain significance (Jun 11, 2021)
12-109085025-C-T		not specified	Uncertain significance (Apr 06, 2022)
12-109085037-C-T		not specified	Uncertain significance (Jun 16, 2023)
12-109085049-C-T		not specified	Uncertain significance (May 13, 2024)
12-109085066-G-A		not specified	Uncertain significance (Jun 10, 2024)
12-109085072-A-G		not specified	Uncertain significance (Dec 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP30	protein_coding	protein_coding	ENST00000257548	13	64938

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000825	0.999	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	222	290	0.764	0.0000159	3351
Missense in Polyphen		74	117.28	0.63096		1365
Synonymous	1.22	101	118	0.857	0.00000678	1018
Loss of Function	2.96	12	29.3	0.409	0.00000148	332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000171	0.000167
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy (PubMed:18287522, PubMed:24896179, PubMed:25527291, PubMed:25621951). Preferentially cleaves 'Lys-6'- and 'Lys-11'- linked polyubiquitin chains, 2 types of linkage that participate to mitophagic signaling (PubMed:25621951). Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65' (PubMed:25527291). Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2 (By similarity). {ECO:0000250|UniProtKB:Q3UN04, ECO:0000269|PubMed:18287522, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:25621951}.
• Pathway: Mitophagy - animal - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.491
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.176
• hipred: N
• hipred_score: 0.488
• ghis: 0.545

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.882

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp30

Gene ontology

• Biological process: autophagy of mitochondrion;ubiquitin-dependent protein catabolic process;mitochondrial fusion;protein deubiquitination;protein K11-linked deubiquitination;protein K6-linked deubiquitination;negative regulation of mitophagy
• Cellular component: mitochondrion;mitochondrial outer membrane;integral component of membrane
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity