USP7

ubiquitin specific peptidase 7, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 16:8892097-8975328

Previous symbols: [ "HAUSP" ]

Links

ENSG00000187555 ∙ NCBI:7874 ∙ OMIM:602519 ∙ HGNC:12630 ∙ Uniprot:Q93009 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hao-Fountain syndrome (Strong), mode of inheritance: AD
• Hao-Fountain syndrome (Strong), mode of inheritance: AD
• Hao-Fountain syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hao-Fountain syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	26365382; 30679821

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP7 gene.

• not provided (4 variants)
• Hao-Fountain syndrome due to USP7 mutation (1 variants)
• Hao-Fountain syndrome (1 variants)
• Neurodevelopmental disorder (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP7 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				59	7	66
missense		4	92	4	3	103
nonsense	4	2	1			7
start loss						0
frameshift	3	5				8
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)	1	2				3
splice region			11	15	5	31
non coding			4	68	31	103
Total	8	13	101	132	41

Variants in USP7

This is a list of pathogenic ClinVar variants found in the USP7 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-8894026-A-C			Likely pathogenic (Dec 14, 2020)
16-8894028-G-GT			Uncertain significance (May 23, 2022)
16-8894076-T-C		USP7-related disorder	Likely benign (Dec 19, 2023)
16-8894087-G-C			Uncertain significance (Aug 16, 2023)
16-8894110-G-A		Inborn genetic diseases	Benign/Likely benign (Sep 09, 2023)
16-8894113-G-T			Uncertain significance (Dec 09, 2023)
16-8894529-CG-C			Benign (Feb 01, 2024)
16-8894529-CGG-C			Benign (Jan 26, 2024)
16-8894529-C-CG		Hao-Fountain syndrome	Benign (Jan 31, 2024)
16-8894529-C-CT			Likely benign (Aug 08, 2022)
16-8894530-G-T			Likely benign (Oct 25, 2023)
16-8894529-C-CGG			Benign (Jan 22, 2024)
16-8894531-G-GC			Benign (Sep 24, 2023)
16-8894531-G-GT			Likely benign (Dec 22, 2023)
16-8894532-G-GC			Likely benign (Aug 17, 2023)
16-8894532-G-GT			Likely benign (Nov 24, 2023)
16-8894533-G-A			Benign (May 25, 2022)
16-8894533-G-C			Likely benign (Jul 24, 2022)
16-8894533-G-T			Likely benign (Dec 07, 2023)
16-8894533-G-GA			Likely benign (Oct 27, 2023)
16-8894533-G-GC			Benign (Oct 13, 2023)
16-8894533-G-GT			Benign (Jan 25, 2024)
16-8894534-G-C			Benign (Jan 24, 2024)
16-8894534-G-GC			Likely benign (Oct 17, 2023)
16-8894534-G-GT			Likely benign (Jul 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP7	protein_coding	protein_coding	ENST00000344836	31	72421

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.71e-12	125739	0	4	125743	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.65	225	621	0.362	0.0000350	7419
Missense in Polyphen		13	197.05	0.065972		2321
Synonymous	-2.44	279	232	1.20	0.0000146	1865
Loss of Function	8.04	1	77.2	0.0130	0.00000473	830

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000355	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:26678539). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC- NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:21745816, PubMed:22411829). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26678539}.
• Pathway: FoxO signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;DNA Repair;Signal Transduction;Gene expression (Transcription);Regulation of PTEN localization;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;Synthesis of active ubiquitin: roles of E1 and E2 enzymes;Ub-specific processing proteases;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;PTEN Regulation;PIP3 activates AKT signaling;Deubiquitination;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Protein ubiquitination;Intracellular signaling by second messengers;Formation of TC-NER Pre-Incision Complex;FoxO family signaling;p53 pathway;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.226

Intolerance Scores

• loftool: 0.0608
• rvis_EVS: -1.33
• rvis_percentile_EVS: 4.67

Haploinsufficiency Scores

• pHI: 0.409
• hipred: Y
• hipred_score: 0.825
• ghis: 0.661

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.809

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp7
• Phenotype: growth/size/body region phenotype; embryo 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: usp7
• Affected structure: caudal fin upper lobe
• Phenotype tag: abnormal
• Phenotype quality: fused with

Gene ontology

• Biological process: transcription-coupled nucleotide-excision repair;ubiquitin-dependent protein catabolic process;multicellular organism development;maintenance of DNA methylation;viral process;protein deubiquitination;regulation of protein stability;negative regulation of NF-kappaB transcription factor activity;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;monoubiquitinated protein deubiquitination;histone H2B conserved C-terminal lysine deubiquitination;protein stabilization;regulation of DNA-binding transcription factor activity;protein K48-linked deubiquitination;positive regulation of DNA demethylation;regulation of telomere capping
• Cellular component: nucleus;nucleoplasm;chromosome;cytosol;nuclear body;PML body;protein-containing complex
• Molecular function: p53 binding;cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;protein C-terminus binding;transcription factor binding;ubiquitin protein ligase binding;thiol-dependent ubiquitinyl hydrolase activity;ubiquitinyl hydrolase activity;Lys48-specific deubiquitinase activity