USP14

ubiquitin specific peptidase 14, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 18:158383-214629

Links

ENSG00000101557 ∙ NCBI:9097 ∙ OMIM:607274 ∙ HGNC:12612 ∙ Uniprot:P54578 ∙ 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 USP14 gene.

• Distal arthrogryposis and CNS involvement (1 variants)
• not provided (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP14 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				4	4	8
missense			14			14
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding					1	1
Total	1	0	14	4	5

Variants in USP14

This is a list of pathogenic ClinVar variants found in the USP14 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-163302-T-C			Likely benign (Jun 29, 2018)
18-163305-C-T			Likely benign (Dec 04, 2018)
18-163341-G-A		not specified	Uncertain significance (Jun 22, 2023)
18-163370-A-G		not specified	Uncertain significance (Nov 09, 2023)
18-163396-G-A			Benign (Dec 31, 2019)
18-163427-G-A		not specified	Uncertain significance (Oct 12, 2022)
18-178964-A-T		not specified	Uncertain significance (Jul 26, 2022)
18-178968-TCTTC-T		Distal arthrogryposis and CNS involvement • See cases	Pathogenic (Aug 26, 2022)
18-179018-A-G		not specified	Uncertain significance (Sep 14, 2023)
18-196637-C-G		not specified	Uncertain significance (Jul 17, 2024)
18-196694-T-C		not specified	Uncertain significance (Apr 29, 2024)
18-198048-C-G		not specified	Uncertain significance (Sep 29, 2023)
18-198075-C-A		not specified	Uncertain significance (Mar 01, 2024)
18-198107-T-A		not specified	Uncertain significance (Sep 12, 2023)
18-199231-A-T		not specified	Uncertain significance (May 14, 2024)
18-199275-A-G		not specified	Uncertain significance (Mar 07, 2023)
18-199291-A-T		not specified	Uncertain significance (Jan 31, 2022)
18-203081-A-C			Benign (Nov 14, 2018)
18-204583-T-C		not specified	Uncertain significance (Jan 16, 2024)
18-204585-T-C			Likely benign (May 08, 2018)
18-204602-G-C			Benign (Dec 31, 2019)
18-204612-G-C		not specified	Uncertain significance (May 12, 2024)
18-210001-G-A		not specified	Uncertain significance (Mar 01, 2024)
18-210389-T-C		not specified	Uncertain significance (Mar 25, 2024)
18-210453-T-C			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP14	protein_coding	protein_coding	ENST00000261601	16	56247

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.905	0.0945	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	170	257	0.661	0.0000130	3258
Missense in Polyphen		40	84.957	0.47083		1106
Synonymous	0.625	80	87.4	0.915	0.00000472	859
Loss of Function	4.45	6	34.0	0.176	0.00000185	400

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000113	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000113	0.000109
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation. {ECO:0000269|PubMed:18162577, ECO:0000269|PubMed:19106094, ECO:0000269|PubMed:19135427, ECO:0000269|PubMed:27666593}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.629
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.668
• hipred: Y
• hipred_score: 0.749
• ghis: 0.640

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.748

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp14
• Phenotype: muscle phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); reproductive system phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;chemical synaptic transmission;negative regulation of endopeptidase activity;protein deubiquitination;innate immune response;regulation of chemotaxis;regulation of proteasomal protein catabolic process;tRNA 5'-end processing;negative regulation of ER-associated ubiquitin-dependent protein catabolic process
• Cellular component: proteasome complex;cytosol;plasma membrane;cell surface;cytoplasmic vesicle;synapse;extracellular exosome
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;endopeptidase inhibitor activity;protein binding;tRNA guanylyltransferase activity;thiol-dependent ubiquitinyl hydrolase activity;proteasome binding