USP19

ubiquitin specific peptidase 19, the group of Ubiquitin specific peptidases|Zinc fingers MYND-type

Basic information

Region (hg38): 3:49108046-49120938

Links

ENSG00000172046 ∙ NCBI:10869 ∙ OMIM:614471 ∙ HGNC:12617 ∙ Uniprot:O94966 ∙ 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 USP19 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP19 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	1	3
missense			81	7		88
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	81	9	1

Variants in USP19

This is a list of pathogenic ClinVar variants found in the USP19 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-49108968-C-T		not specified	Uncertain significance (Aug 14, 2024)
3-49109005-C-T		not specified	Uncertain significance (Mar 02, 2023)
3-49109010-G-C		not specified	Uncertain significance (Feb 22, 2023)
3-49109046-C-T		not specified	Uncertain significance (Jun 28, 2023)
3-49109071-T-A		not specified	Uncertain significance (Sep 01, 2021)
3-49109119-C-T		not specified	Uncertain significance (Jun 21, 2023)
3-49109127-C-T		not specified	Uncertain significance (Jun 02, 2023)
3-49109135-C-T			Likely benign (Oct 24, 2018)
3-49110192-C-T		not specified	Uncertain significance (Nov 10, 2024)
3-49110222-G-A		not specified	Uncertain significance (Apr 20, 2023)
3-49110273-G-A		not specified	Uncertain significance (Feb 28, 2023)
3-49110321-C-T		not specified	Uncertain significance (Nov 09, 2024)
3-49110329-G-A		not specified	Uncertain significance (Sep 04, 2024)
3-49110452-C-G		not specified	Uncertain significance (Jul 06, 2024)
3-49110561-G-T		not specified	Uncertain significance (Aug 10, 2023)
3-49110703-C-A			Benign (Oct 24, 2018)
3-49110781-G-A		not specified	Uncertain significance (Aug 09, 2021)
3-49110846-T-C		not specified	Uncertain significance (Apr 07, 2023)
3-49111001-T-A		not specified	Uncertain significance (Apr 17, 2024)
3-49111008-G-C		not specified	Uncertain significance (Mar 20, 2023)
3-49111025-C-T		not specified	Uncertain significance (Jul 26, 2022)
3-49111038-C-T		not specified	Uncertain significance (Jan 06, 2023)
3-49111103-C-T		not specified	Uncertain significance (Oct 19, 2024)
3-49111146-C-A		not specified	Uncertain significance (Oct 02, 2023)
3-49111148-A-G		not specified	Uncertain significance (Oct 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP19	protein_coding	protein_coding	ENST00000434032	26	12893

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000526	124790	0	12	124802	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.99	691	855	0.808	0.0000532	9131
Missense in Polyphen		219	331.42	0.66078		3515
Synonymous	1.63	298	336	0.887	0.0000198	2966
Loss of Function	6.66	7	64.9	0.108	0.00000332	733

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000163	0.000161
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000378	0.0000353
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000654	0.0000654
Other	0.000167	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin- dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic- reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non- catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked ubiquitin chains. {ECO:0000269|PubMed:19465887, ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:22128162, ECO:0000269|PubMed:22689415}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination (Consensus)

Intolerance Scores

• loftool: 0.318
• rvis_EVS: -1.59
• rvis_percentile_EVS: 3.11

Haploinsufficiency Scores

• pHI: 0.174
• hipred: Y
• hipred_score: 0.794
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.672

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp19
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: usp19
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: protein deubiquitination;ubiquitin-dependent ERAD pathway;regulation of protein stability;response to endoplasmic reticulum stress;negative regulation of skeletal muscle tissue development;protein stabilization;protein K48-linked deubiquitination;positive regulation of cell cycle process;regulation of cellular response to hypoxia;negative regulation of proteasomal protein catabolic process;regulation of ERAD pathway
• Cellular component: endoplasmic reticulum membrane;cytosol;integral component of membrane
• Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;ubiquitin protein ligase binding;thiol-dependent ubiquitinyl hydrolase activity;metal ion binding;Hsp90 protein binding;Lys48-specific deubiquitinase activity