USP45

Chr 6AR

ubiquitin specific peptidase 45

Also known as: LCA19

NCBI Gene: 85015ENSG00000123552UniProt: Q70EL2

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]

Primary Disease Associations & Inheritance

?Leber congenital amaurosis 19MIM #618513
AR
171
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— USP45
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 118 VUS of 171 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.06LOEUF
pLI 0.000
Z-score 1.27
OE 0.78 (0.59–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.64Z-score
OE missense 0.91 (0.83–0.99)
367 obs / 403.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.78 (0.59–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.83–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 31 / 39.6Missense obs/exp: 367 / 403.3Syn Z: 1.18

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic6
VUS118
Likely Benign16
Benign12
19
Pathogenic
6
Likely Pathogenic
118
VUS
16
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
18
0
19
Likely Pathogenic
1
3
2
0
6
VUS
5
101
12
0
118
Likely Benign
1
12
0
3
16
Benign
1
5
2
4
12
Total8122347171

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

USP45 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

USP45-related Leber congenital amaurosis

strong
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Leber congenital amaurosis 19

MIM #618513

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance.
Liu L et al.·Adv Sci (Weinh)
2023
USP45 Represses Melanoma Development by Deubiquitinating and Stabilizing Tumor Suppressor MRGPRF.
Zhang W et al.·Adv Sci (Weinh)
2025
Deubiquitinase USP45 stabilizes RTCB and DDX1, promoting tumorigenesis and chemoresistance.
Sun W et al.·Int J Biol Macromol
2026
Biallelic mutations in USP45, encoding a deubiquitinating enzyme, are associated with Leber congenital amaurosis.
Yi Z et al.·J Med Genet
2019
Familial Multiple Myeloma: Insights From Epidemiology and Underlying Germline Genetic Predisposition to the Clinic.
Akkus E et al.·Clin Lymphoma Myeloma Leuk
2025Review
Novel pedigree analysis implicates DNA repair and chromatin remodeling in multiple myeloma risk.
Waller RG et al.·PLoS Genet
2018Functional
p19-Targeting ILP Protein Blockers of IL-23/Th-17 Pro-Inflammatory Axis Displayed on Engineered Bacteria of Food Origin.
Škrlec K et al.·Int J Mol Sci
2018
[Construction and identification of recombinant Lactococcus lactis highly expressing human granulocyte-macrophage colony stimulating factor].
Ma GF et al.·Nan Fang Yi Ke Da Xue Xue Bao
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools