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.

• Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss (8 variants)
• Cholestasis (8 variants)
• not provided (5 variants)
• Cholestasis, progressive familial intrahepatic, (PFIC4-like) (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.

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				14	6	20
missense	1	2	50	6	8	67
nonsense	4	4				8
start loss						0
frameshift	8	4				12
inframe indel						0
splice donor/acceptor (+/-2bp)	2	5				7
splice region		1	1	2	1	5
non coding				4	3	7
Total	15	15	50	24	17

Highest pathogenic variant AF is 0.0000855

Variants in USP53

This is a list of pathogenic ClinVar variants found in the USP53 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-119239763-G-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
4-119239779-T-TA			Pathogenic (Jul 05, 2022)
4-119239836-T-TAG		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Likely pathogenic (Sep 01, 2022)
4-119239866-CA-C			Pathogenic (May 27, 2022)
4-119239915-A-C			Likely benign (Nov 17, 2023)
4-119245325-CCTGTTTTTTAGGTTTTATGGCAATTGGATATATT-C		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss • USP53-related disorder	Likely pathogenic (Mar 25, 2024)
4-119245338-T-A		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Uncertain significance (Mar 26, 2024)
4-119245345-G-A		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Likely pathogenic (Oct 10, 2022)
4-119245350-T-A		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Likely pathogenic (Mar 22, 2022)
4-119245361-C-T		Cholestasis • Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Pathogenic (Oct 15, 2019)
4-119245365-G-A		Premature ovarian insufficiency	Uncertain significance (Jan 10, 2018)
4-119245397-C-T		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Likely pathogenic (Jan 03, 2022)
4-119245430-G-A		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Likely pathogenic (Mar 01, 2023)
4-119248751-A-T			Benign (Aug 01, 2024)
4-119248787-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
4-119248790-C-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
4-119248796-G-C		Inborn genetic diseases	Uncertain significance (May 01, 2024)
4-119248799-A-G		Inborn genetic diseases	Uncertain significance (Aug 19, 2023)
4-119248807-G-T		Cholestasis • Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Pathogenic (Oct 15, 2019)
4-119248821-A-C		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
4-119248841-C-T		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Likely pathogenic (Mar 22, 2022)
4-119248842-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
4-119248873-G-A			Likely benign (Jun 04, 2023)
4-119248881-T-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
4-119248882-TGTAA-T		Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	Uncertain significance (Feb 14, 2023)

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