USP48

ubiquitin specific peptidase 48, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 1:21678298-21783606

Previous symbols: [ "USP31" ]

Links

ENSG00000090686 ∙ NCBI:84196 ∙ OMIM:617445 ∙ HGNC:18533 ∙ Uniprot:Q86UV5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• hearing loss, autosomal dominant 85 (Limited), mode of inheritance: AD
• hearing loss, autosomal dominant 85 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 85	AD	Audiologic/Otolaryngologic	The condition has described as involving early-onset hearing loss in some individuals, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	34059922

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP48 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP48 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		2
missense			26	1		27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	26	3	1

Variants in USP48

This is a list of pathogenic ClinVar variants found in the USP48 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-21687227-T-C		USP48-related condition	Uncertain significance (Aug 05, 2024)
1-21690003-C-T		not specified	Uncertain significance (Dec 11, 2023)
1-21695104-C-T		not specified	Uncertain significance (Jun 10, 2024)
1-21695203-G-A		not specified	Uncertain significance (Dec 01, 2022)
1-21701583-G-A		not specified	Uncertain significance (Jun 28, 2022)
1-21703628-A-G			Benign (Jul 24, 2017)
1-21704318-G-A		not specified	Likely benign (Dec 21, 2023)
1-21704322-T-C		not specified	Uncertain significance (Oct 26, 2022)
1-21704398-C-CA		USP48-related condition	Likely benign (May 29, 2024)
1-21706177-A-G		not specified	Uncertain significance (Mar 29, 2022)
1-21706183-G-A		not specified	Uncertain significance (Feb 22, 2023)
1-21706183-GT-AA		Hearing loss, autosomal dominant 85	Pathogenic (Jan 27, 2023)
1-21706184-T-A		not specified	Uncertain significance (Feb 22, 2023)
1-21715390-A-G			Benign (Nov 01, 2023)
1-21715452-A-T		not specified	Uncertain significance (Dec 07, 2021)
1-21721128-C-A		not specified	Uncertain significance (Jan 30, 2024)
1-21721134-A-G		not specified	Uncertain significance (Feb 22, 2023)
1-21721716-C-T		not specified	Uncertain significance (May 18, 2022)
1-21721721-T-C		not specified	Uncertain significance (Jun 17, 2022)
1-21721753-A-C		not specified	Uncertain significance (Jun 01, 2023)
1-21723934-A-G		not specified	Uncertain significance (Jan 23, 2024)
1-21723940-C-T		not specified	Uncertain significance (Jun 02, 2023)
1-21723973-A-G		not specified	Uncertain significance (May 27, 2022)
1-21723984-G-A			Uncertain significance (Sep 25, 2017)
1-21723997-C-T		not specified	Uncertain significance (Dec 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP48	protein_coding	protein_coding	ENST00000308271	27	105309

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.61e-7	125738	0	9	125747	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.37	256	543	0.472	0.0000281	6832
Missense in Polyphen		27	113.85	0.23716		1430
Synonymous	0.719	179	192	0.934	0.0000104	1796
Loss of Function	6.92	5	65.4	0.0764	0.00000325	813

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000408	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recognizes and hydrolyzes the peptide bond at the C- terminal Gly of ubiquitin. Involved in the processing of poly- ubiquitin precursors as well as that of ubiquitinated proteins. May be involved in the regulation of NF-kappa-B activation by TNF receptor superfamily via its interactions with RELA and TRAF2. May also play a regulatory role at postsynaptic sites. {ECO:0000269|PubMed:16214042}.

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.533
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.101
• hipred: Y
• hipred_score: 0.728
• ghis: 0.629

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.868

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp48

Zebrafish Information Network

• Gene name: usp48
• Affected structure: pharyngeal arch cartilage
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein deubiquitination
• Cellular component: nucleoplasm;mitochondrion;cytosol
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity