USP4

ubiquitin specific peptidase 4, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 3:49277144-49340712

Previous symbols: [ "UNP" ]

Links

ENSG00000114316 ∙ NCBI:7375 ∙ OMIM:603486 ∙ HGNC:12627 ∙ Uniprot:Q13107 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP4 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				5		5
missense			45	1	2	48
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	45	6	2

Variants in USP4

This is a list of pathogenic ClinVar variants found in the USP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-49278349-T-C		not specified	Likely benign (Mar 18, 2024)
3-49278410-A-C		not specified	Uncertain significance (May 10, 2022)
3-49278426-T-C		not specified	Uncertain significance (Jul 12, 2023)
3-49278438-T-G		not specified	Uncertain significance (Mar 16, 2024)
3-49278843-C-T		not specified	Uncertain significance (Sep 30, 2021)
3-49280761-G-T		not specified	Uncertain significance (Apr 18, 2023)
3-49280786-T-C		not specified	Uncertain significance (Jan 26, 2022)
3-49280823-G-A			Likely benign (Mar 29, 2018)
3-49283991-T-C			Benign (Aug 08, 2017)
3-49284003-C-T		not specified	Uncertain significance (Aug 13, 2021)
3-49284004-G-A			Likely benign (Mar 29, 2018)
3-49284048-G-A		not specified	Uncertain significance (May 23, 2023)
3-49284054-G-A		not specified	Uncertain significance (Mar 15, 2024)
3-49284057-G-A		not specified	Uncertain significance (Jan 23, 2024)
3-49284475-T-C		not specified	Uncertain significance (Dec 17, 2023)
3-49284497-T-C		not specified	Uncertain significance (Dec 20, 2021)
3-49284565-C-G		not specified	Uncertain significance (Jan 17, 2023)
3-49284880-C-T		not specified	Uncertain significance (Feb 17, 2023)
3-49286122-C-T		not specified	Uncertain significance (Dec 11, 2023)
3-49286127-G-C		not specified	Uncertain significance (Dec 12, 2023)
3-49286225-C-A		not specified	Uncertain significance (Jul 28, 2021)
3-49286229-C-T		not specified	Uncertain significance (Jan 02, 2024)
3-49286260-T-C		not specified	Uncertain significance (May 29, 2024)
3-49286299-G-C		not specified	Uncertain significance (Jan 24, 2024)
3-49286314-C-T		not specified	Uncertain significance (Sep 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP4	protein_coding	protein_coding	ENST00000265560	22	62882

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.61e-9	1.00	125624	0	124	125748	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	469	541	0.867	0.0000290	6349
Missense in Polyphen		110	161.16	0.68253		1883
Synonymous	1.48	182	209	0.870	0.0000117	1807
Loss of Function	3.71	24	53.2	0.451	0.00000254	633

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000452	0.000452
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000489	0.000489
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000768	0.000765
Middle Eastern	0.000489	0.000489
South Asian	0.000294	0.000294
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3. This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. May also play a role in the regulation of quality control in the ER. {ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:16339847, ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:20595234, ECO:0000269|PubMed:7784062}.
• Pathway: Signal Transduction;Post-translational protein modification;Metabolism of proteins;TNFR1-induced NFkappaB signaling pathway;TNFR1-induced proapoptotic signaling;TNF signaling;Ub-specific processing proteases;Deubiquitination;Death Receptor Signalling (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.884
• rvis_EVS: -0.82
• rvis_percentile_EVS: 12.01

Haploinsufficiency Scores

• pHI: 0.167
• hipred: Y
• hipred_score: 0.648
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.913

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp4
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: usp4
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: spliceosomal tri-snRNP complex assembly;ubiquitin-dependent protein catabolic process;protein deubiquitination;negative regulation of protein ubiquitination;regulation of protein stability;protein localization to cell surface
• Cellular component: nucleus;cytoplasm;lysosome;cytosol;plasma membrane
• Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;adenosine receptor binding;thiol-dependent ubiquitinyl hydrolase activity;identical protein binding;metal ion binding