GeneBe

USP30

protein-coding

ubiquitin specific peptidase 30, the group of Ubiquitin specific peptidases

Gene summary

USP30, a member of the ubiquitin-specific protease family (see USP1, MIM 603478), is a novel mitochondrial deubiquitinating (DUB) enzyme (Nakamura and Hirose, 2008 [PubMed 18287522]).[supplied by OMIM, Dec 2008]

MANE transcript

NM_032663.5

Inheritance

—

ClinVar variants

U:74B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr12:109,023,089-109,088,023

External References & Databases

Ensembl (ENSG00000135093)NCBI Gene (84749)OMIM (612492)HGNC:20065GenCCUniProt (Q70CQ3)AlphaFoldClinVar (USP30)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~64.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to USP30 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 65
not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032663.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
1
clinvar
 3
missense
66
clinvar
1
clinvar
 67
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total00741176
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_032663.5RefSeqNP_116052.213MANE Select
ENST00000257548.10EnsemblENSP00000257548.513MANE Select
NM_001301175.2RefSeqNP_001288104.112Standard
ENST00000377883.7EnsemblENSP00000473942.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Mitophagy - animal - Homo sapiens (human)
  • Post-translational protein modification
  • Metabolism of proteins
  • Ub-specific processing proteases
  • Deubiquitination

Biological Process

  • autophagy of mitochondrion
  • ubiquitin-dependent protein catabolic process
  • mitochondrial fusion
  • protein deubiquitination
  • protein K11-linked deubiquitination

Molecular Function

  • cysteine-type endopeptidase activity
  • thiol-dependent ubiquitin-specific protease activity
  • thiol-dependent ubiquitinyl hydrolase activity

Cellular Component

  • mitochondrion
  • mitochondrial outer membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000257548
Coding exons
13
Length
64938
Individuals with no LoFs
125719
Homozygous LoFs
0
Heterozygous LoFs
29
Defined
125748
p
0.000115
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.432222900.7640.00001593351
Missense (PolyPhen)74117.280.630961365
Synonymous1.221011180.8570.000006781018
Loss of Function2.961229.30.4090.00000148332

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.000170.00017rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.110

Intolerance Scores

LoFtool
0.491
RVIS EVS
-0.14
RVIS percentile EVS
43.77

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.882

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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