USP6

ubiquitin specific peptidase 6, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 17:5116032-5175034

Previous symbols: [ "HRP1", "TRESMCR" ]

Links

ENSG00000129204

∙ NCBI:9098 ∙ OMIM:604334 ∙ HGNC:12629 ∙ Uniprot:P35125 ∙ 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 USP6 gene.

not_specified (176 variants)
not_provided (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001304284.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	3 clinvar	7
missense			170 clinvar	6 clinvar	2 clinvar	178
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	0	0	170	10	6

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP6	protein_coding	protein_coding	ENST00000574788	29	58597

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.95e-35	0.00770	124183	11	1554	125748	0.00624

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.142	792	781	1.01	0.0000439	9244
Missense in Polyphen		260	278.65	0.93308		3591
Synonymous	-0.495	299	288	1.04	0.0000165	2623
Loss of Function	1.74	63	79.8	0.790	0.00000455	867

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0508	0.0507
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00158	0.00152
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.00360	0.00352
Middle Eastern	0.00158	0.00152
South Asian	0.00515	0.00508
Other	0.00471	0.00457

dbNSFP

Source: dbNSFP

Function: FUNCTION: Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6- dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation. {ECO:0000269|PubMed:15509780, ECO:0000269|PubMed:16127172, ECO:0000269|PubMed:20418905}.;
Disease: DISEASE: Note=A chromosomal aberration involving USP6 is a common genetic feature of aneurysmal bone cyst, a benign osseous neoplasm. Translocation t(16;17)(q22;p13) with CDH11. The translocation generates a fusion gene in which the strong CDH11 promoter is fused to the entire USP6 coding sequence, resulting in USP6 transcriptional up-regulation (PubMed:15026324). {ECO:0000269|PubMed:15026324}.;
Pathway: Arf6 signaling events (Consensus)

Intolerance Scores

loftool: 0.996
rvis_EVS: 0.42
rvis_percentile_EVS: 76.96

Haploinsufficiency Scores

pHI: 0.0483
hipred: N
hipred_score: 0.309
ghis: 0.465

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.423

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

Biological process: cellular protein modification process;ubiquitin-dependent protein catabolic process;intracellular protein transport;protein deubiquitination;regulation of vesicle-mediated transport;activation of GTPase activity
Cellular component: cytoplasm;lysosome;plasma membrane;recycling endosome
Molecular function: nucleic acid binding;cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;GTPase activator activity;protein binding;calmodulin binding;Rab GTPase binding