USP53

ubiquitin specific peptidase 53, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 4:119212587-119295518

Links

ENSG00000145390

∙ NCBI:54532 ∙ OMIM:617431 ∙ HGNC:29255 ∙ Uniprot:Q70EK8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cholestasis (Strong), mode of inheritance: AR
cholestasis, progressive familial intrahepatic, 7, with or without hearing loss (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	AR	Audiologic/Otolaryngologic; Gastrointestinal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Rifampicin has been described as effective for pruritis; Medical management has been described as beneficial as pertains to cholestasis and related sequelae; Liver transplant has been described	Audiologic/Otolaryngologic; Gastrointestinal	30250217; 32124521; 33075013

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP53 gene.

Inborn_genetic_diseases (104 variants)
not_provided (72 variants)
Cholestasis,_progressive_familial_intrahepatic,_7,_with_or_without_hearing_loss (37 variants)
Cholestasis (10 variants)
USP53-related_disorder (4 variants)
Premature_ovarian_insufficiency (3 variants)
Cholestasis,_progressive_familial_intrahepatic,_(PFIC4-like) (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP53 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001371395.1. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	14 clinvar	5 clinvar	20
missense	2 clinvar	3 clinvar	107 clinvar	15 clinvar	6 clinvar	133
nonsense	4 clinvar	7 clinvar	1 clinvar			12
start loss						0
frameshift	10 clinvar	5 clinvar				15
splice donor/acceptor (+/-2bp)	1 clinvar	6 clinvar				7
Total	17	21	109	29	11

Highest pathogenic variant AF is 0.000066961475

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP53	protein_coding	protein_coding	ENST00000450251	15	82931

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.66e-13	0.997	124685	0	108	124793	0.000433

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.982	496	562	0.883	0.0000280	7162
Missense in Polyphen		155	184.4	0.84055		2297
Synonymous	1.41	165	190	0.870	0.00000923	1924
Loss of Function	2.83	29	50.8	0.571	0.00000287	628

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00107	0.00106
Ashkenazi Jewish	0.00	0.00
East Asian	0.000723	0.000723
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000338	0.000335
Middle Eastern	0.000723	0.000723
South Asian	0.000890	0.000883
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Tight junction-associated protein that is involved in the survival of auditory hair cells and hearing. Maybe by modulating the barrier properties and mechanical stability of tight junctions (By similarity). Has no peptidase activity (PubMed:14715245). {ECO:0000250|UniProtKB:P15975, ECO:0000269|PubMed:14715245}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

loftool: 0.913
rvis_EVS: 0.83
rvis_percentile_EVS: 88.11

Haploinsufficiency Scores

pHI: 0.256
hipred: N
hipred_score: 0.371
ghis: 0.464

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.812

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Usp53
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: usp53a
Affected structure: post-vent region
Phenotype tag: abnormal
Phenotype quality: curled

Gene ontology

Biological process: action potential;sensory perception of sound;biological_process;response to auditory stimulus;protein deubiquitination;neuron apoptotic process
Cellular component: cellular_component;bicellular tight junction
Molecular function: protein binding;thiol-dependent ubiquitinyl hydrolase activity