USP28

ubiquitin specific peptidase 28, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 11:113797874-113875572

Links

ENSG00000048028 ∙ NCBI:57646 ∙ OMIM:610748 ∙ HGNC:12625 ∙ Uniprot:Q96RU2 ∙ 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 USP28 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP28 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				1	1	2
missense			53	1		54
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	53	2	1

Variants in USP28

This is a list of pathogenic ClinVar variants found in the USP28 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-113799350-C-T		not specified	Uncertain significance (Apr 08, 2022)
11-113799392-C-G		not specified	Uncertain significance (Oct 06, 2021)
11-113799400-C-T		not specified	Uncertain significance (Apr 13, 2023)
11-113801625-T-A			Benign (Aug 03, 2017)
11-113803174-C-T		not specified	Uncertain significance (Dec 27, 2023)
11-113803190-C-T		not specified	Uncertain significance (Oct 26, 2021)
11-113803198-T-A		not specified	Uncertain significance (Mar 06, 2023)
11-113803207-C-T		not specified	Uncertain significance (Dec 01, 2022)
11-113803208-G-A		not specified	Uncertain significance (May 24, 2023)
11-113803217-C-T		not specified	Uncertain significance (Feb 17, 2024)
11-113803221-C-G		not specified	Uncertain significance (May 18, 2023)
11-113803250-C-T		not specified	Uncertain significance (Sep 04, 2024)
11-113803851-G-T		not specified	Uncertain significance (Aug 04, 2023)
11-113804722-G-A		not specified	Uncertain significance (Nov 21, 2022)
11-113804747-T-C		not specified	Uncertain significance (Apr 29, 2024)
11-113806508-G-A		not specified	Uncertain significance (Jul 13, 2021)
11-113806543-T-C		not specified	Uncertain significance (Apr 24, 2024)
11-113806566-T-A		not specified	Uncertain significance (Jan 10, 2023)
11-113806566-T-C		not specified	Uncertain significance (Nov 11, 2024)
11-113808338-C-T		not specified	Likely benign (May 26, 2022)
11-113808386-G-A		not specified	Uncertain significance (Dec 22, 2023)
11-113808437-T-C		not specified	Uncertain significance (Jan 20, 2023)
11-113809158-T-C		not specified	Uncertain significance (Feb 22, 2023)
11-113809167-C-T		not specified	Uncertain significance (Jan 08, 2024)
11-113809182-T-C		not specified	Uncertain significance (Apr 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP28	protein_coding	protein_coding	ENST00000003302	25	77697

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.53e-13	1.00	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	484	563	0.860	0.0000286	7074
Missense in Polyphen		159	219.38	0.72478		2796
Synonymous	0.538	191	201	0.952	0.0000101	2020
Loss of Function	3.93	32	66.7	0.480	0.00000395	734

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000818	0.000815
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000381	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000389	0.000387
Middle Eastern	0.000381	0.000381
South Asian	0.000131	0.000131
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306). {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:24623306}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.763
• rvis_EVS: -0.79
• rvis_percentile_EVS: 12.6

Haploinsufficiency Scores

• pHI: 0.608
• hipred: Y
• hipred_score: 0.706
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.725

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp28
• Phenotype: immune system phenotype; hematopoietic system phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: usp28
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: DNA damage checkpoint;DNA repair;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;Ras protein signal transduction;cell population proliferation;response to ionizing radiation;protein deubiquitination;regulation of protein stability;cellular response to UV;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• Cellular component: nucleoplasm;cytosol;nuclear body;protein-containing complex
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;thiol-dependent ubiquitinyl hydrolase activity