GeneBe

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

  • complex neurodevelopmental disorder (Moderate), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP14 gene.

  • not_specified (37 variants)
  • not_provided (11 variants)
  • Distal_arthrogryposis_and_CNS_involvement (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. These statistics are base on transcript: NM_000005151.4. 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
4
clinvar
 8
missense
41
clinvar
 41
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total 1 0 43 4 4
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
USP14protein_codingprotein_codingENST00000261601 1656247
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.9050.09451257330141257470.0000557
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.941702570.6610.00001303258
Missense in Polyphen4084.9570.470831106
Synonymous0.6258087.40.9150.00000472859
Loss of Function4.45634.00.1760.00000185400

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001160.000116
Ashkenazi Jewish0.00009930.0000992
East Asian0.0001130.000109
Finnish0.00004620.0000462
European (Non-Finnish)0.00001760.0000176
Middle Eastern0.0001130.000109
South Asian0.0001340.000131
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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