USP45

ubiquitin specific peptidase 45, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 6:99432325-99521728

Links

ENSG00000123552 ∙ NCBI:85015 ∙ OMIM:618439 ∙ HGNC:20080 ∙ Uniprot:Q70EL2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• Leber congenital amaurosis 9 (Strong), mode of inheritance: AR
• leber congenital amaurosis 19 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 19	AR	General	Leber congenital amaurosis 19	Ophthalmologic	30573563

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP45 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP45 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				2	4	6
missense			41	6	7	54
nonsense			2			2
start loss						0
frameshift			1	1		2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding					2	2
Total	0	0	44	9	13

Variants in USP45

This is a list of pathogenic ClinVar variants found in the USP45 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-99435724-C-T		not specified	Likely benign (Feb 11, 2022)
6-99435734-G-T		not specified	Uncertain significance (Aug 22, 2023)
6-99435781-C-A		not specified	Uncertain significance (Jan 29, 2024)
6-99435828-T-C		Leber congenital amaurosis 19	Benign (Dec 05, 2021)
6-99435837-G-A		not specified	Uncertain significance (Nov 13, 2024)
6-99435841-T-A		Retinal dystrophy	Uncertain significance (Jan 01, 2022)
6-99437248-G-A		not specified	Uncertain significance (Oct 06, 2024)
6-99437249-G-A		not specified	Uncertain significance (Aug 12, 2021)
6-99437249-G-C		not specified	Uncertain significance (Dec 03, 2024)
6-99437278-G-A		not specified	Likely benign (Oct 10, 2023)
6-99437312-A-G		not specified	Uncertain significance (Feb 28, 2023)
6-99437338-G-A		Laterality defects, autosomal dominant • not specified	Uncertain significance (Aug 21, 2024)
6-99437370-G-T		Retinal dystrophy	Uncertain significance (Jan 01, 2022)
6-99439801-C-T		not specified	Uncertain significance (Oct 21, 2021)
6-99439831-T-G		not specified	Uncertain significance (Nov 23, 2021)
6-99439839-C-A		not specified	Uncertain significance (Dec 20, 2023)
6-99439839-C-T		not specified	Uncertain significance (Nov 24, 2024)
6-99443564-C-A		Retinal dystrophy	Uncertain significance (Jan 01, 2022)
6-99443599-G-A		Retinal dystrophy • not specified	Uncertain significance (Jan 24, 2023)
6-99443620-A-G		not specified	Uncertain significance (Jun 26, 2024)
6-99443648-C-A		Short stature	Pathogenic (Nov 18, 2001)
6-99445808-G-C		not specified	Uncertain significance (May 05, 2023)
6-99445822-C-A		USP45-related disorder	Likely benign (May 31, 2022)
6-99445833-T-C		not specified	Uncertain significance (Aug 28, 2024)
6-99445839-T-A		not specified	Uncertain significance (Jan 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP45	protein_coding	protein_coding	ENST00000327681	17	89415

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.36e-17	0.144	122152	28	3568	125748	0.0144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.642	367	403	0.910	0.0000193	5349
Missense in Polyphen		135	159.7	0.84534		2229
Synonymous	1.18	123	141	0.873	0.00000691	1466
Loss of Function	1.27	31	39.6	0.783	0.00000196	545

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0200	0.0197
Ashkenazi Jewish	0.00241	0.00228
East Asian	0.00439	0.00430
Finnish	0.00513	0.00407
European (Non-Finnish)	0.0219	0.0196
Middle Eastern	0.00439	0.00430
South Asian	0.0235	0.0213
Other	0.0185	0.0161

dbNSFP

Source: dbNSFP

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

Recessive Scores

• pRec: 0.0792

Intolerance Scores

• loftool: 0.929
• rvis_EVS: 1.67
• rvis_percentile_EVS: 96.31

Haploinsufficiency Scores

• pHI: 0.0491
• hipred: N
• hipred_score: 0.174
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.347

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Usp45

Zebrafish Information Network

• Gene name: usp45
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: DNA repair;ubiquitin-dependent protein catabolic process;protein deubiquitination;global genome nucleotide-excision repair
• Cellular component: nucleus;nucleoplasm;cytoplasm
• Molecular function: thiol-dependent ubiquitin-specific protease activity;zinc ion binding