GeneBe

USP45

protein-coding

ubiquitin specific peptidase 45, the group of Ubiquitin specific peptidases

Gene summary

The protein encoded by this gene is a deubiquitylase that binds ERCC1, the catalytic subunit of the XPF-ERCC1 DNA repair endonuclease. This endonuclease is a critical regulator of DNA repair processes, and the deubiquitylase activity of the encoded protein is important for maintaining the DNA repair ability of XPF-ERCC1. [provided by RefSeq, Sep 2016]

MANE transcript

NM_001346022.3

Inheritance

AD, AR

ClinVar variants

P:12U:118B:23

Top phenotype

Leber congenital amaurosis 19

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr6:99,432,325-99,521,728

External References & Databases

Ensembl (ENSG00000123552)NCBI Gene (85015)OMIM (618439)HGNC:20080GenCCUniProt (Q70EL2)AlphaFoldClinVar (USP45)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~89.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Leber congenital amaurosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018998

Submitter: Orphanet

Leber congenital amaurosis 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032794

Submitter: PanelApp Australia

Leber congenital amaurosis 19LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032794

Submitter: Labcorp Genetics (formerly Invitae)

Leber congenital amaurosis 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032794

Submitter: G2P

Clinical Genomic Database (CGD)

Leber congenital amaurosis 19AR

Manifestation: Ophthalmologic

Intervention: General

Rationale: Leber congenital amaurosis 19

Refs: 30573563Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to USP45 variants in ClinVar

10 Conditions Cataloged
not specifiedTotal: 117
not providedTotal: 12
Leber congenital amaurosis 19Total: 11
Retinal dystrophyTotal: 10
Short statureTotal: 4
Leber congenital amaurosisTotal: 3
USP45-related disorderTotal: 2
Optic atrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001346022.3. 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
1
clinvar
3
clinvar
3
clinvar
 7
missense
1
clinvar
3
clinvar
105
clinvar
12
clinvar
2
clinvar
 123
nonsense
2
clinvar
3
clinvar
3
clinvar
1
clinvar
 9
start loss
0
frameshift
3
clinvar
3
clinvar
1
clinvar
 7
splice donor/acceptor (+/-2bp)
6
clinvar
1
clinvar
 7
Total39118167153

Highest pathogenic variant AF is 0.0016020046

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001346022.3RefSeqNP_001332951.117MANE Select
ENST00000500704.7EnsemblENSP00000424372.117MANE Select
NM_001080481.3RefSeqNP_001073950.117Standard
NM_001346021.3RefSeqNP_001332950.117Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
usp45Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • DNA Repair
  • Formation of Incision Complex in GG-NER
  • Global Genome Nucleotide Excision Repair (GG-NER)
  • Nucleotide Excision Repair

Biological Process

  • DNA repair
  • ubiquitin-dependent protein catabolic process
  • protein deubiquitination
  • global genome nucleotide-excision repair

Molecular Function

  • thiol-dependent ubiquitin-specific protease activity
  • zinc ion binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000327681
Coding exons
17
Length
89415
Individuals with no LoFs
122152
Homozygous LoFs
28
Heterozygous LoFs
3568
Defined
125748
p
0.0144
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6423674030.9100.00001935349
Missense (PolyPhen)135159.70.845342229
Synonymous1.181231410.8730.000006911466
Loss of Function1.273139.60.7830.00000196545

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0110.010notable
Latino/Admixed American0.00940.0084notable
Ashkenazi Jewish0.00240.0023notable
East Asian0.00440.0043notable
Finnish0.00510.0041notable
European (Non-Finnish)0.0220.020notable
South Asian0.0240.021notable
Other0.0180.016notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec
0.0792

Intolerance Scores

LoFtool
0.929
RVIS EVS
1.67
RVIS percentile EVS
96.31

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.347

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh
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