UCHL3

ubiquitin C-terminal hydrolase L3, the group of Ubiquitin C-terminal hydrolases

Basic information

Region (hg38): 13:75549483-75606020

Links

ENSG00000118939

∙ NCBI:7347 ∙ OMIM:603090 ∙ HGNC:12515 ∙ Uniprot:P15374 ∙ 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 UCHL3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UCHL3 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						0
missense			8 clinvar			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in UCHL3

This is a list of pathogenic ClinVar variants found in the UCHL3 region.

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

Position	Phenotype	Significance	ClinVar
13-75560783-T-C	not specified	Uncertain significance (Feb 27, 2024)	3185939
13-75560828-A-C	not specified	Uncertain significance (Dec 20, 2023)	3185936
13-75560828-A-G	not specified	Uncertain significance (Feb 23, 2023)	2488793
13-75560865-T-A	not specified	Uncertain significance (May 30, 2023)	2552583
13-75566726-A-G	not specified	Uncertain significance (Jul 07, 2022)	2300062
13-75566733-A-C	not specified	Uncertain significance (Jan 22, 2024)	3185937
13-75566785-A-G	not specified	Uncertain significance (Dec 01, 2022)	2330772
13-75567228-A-C	not specified	Uncertain significance (Sep 27, 2021)	2252593

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UCHL3	protein_coding	protein_coding	ENST00000377595	9	56467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.34e-8	0.331	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	87	119	0.732	0.00000576	1509
Missense in Polyphen		24	46.258	0.51883		595
Synonymous	0.0719	40	40.6	0.986	0.00000196	413
Loss of Function	0.653	13	15.8	0.823	8.52e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000403	0.000381
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.000162	0.000158
Middle Eastern	0.000403	0.000381
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin- signaling and insulin-induced adipogenesis. Required for stress- response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. {ECO:0000269|PubMed:19154770, ECO:0000269|PubMed:21762696, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:2530630, ECO:0000269|PubMed:9790970}.;
Pathway: Proteasome Degradation;Post-translational protein modification;Metabolism of proteins;Synthesis of active ubiquitin: roles of E1 and E2 enzymes;UCH proteinases;Neddylation;Deubiquitination;Protein ubiquitination (Consensus)

Recessive Scores

pRec: 0.120

Intolerance Scores

loftool: 0.726
rvis_EVS: -0.16
rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

pHI: 0.615
hipred: Y
hipred_score: 0.603
ghis: 0.626

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Uchl3
Phenotype: cellular phenotype; muscle phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); digestive/alimentary 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); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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);

Zebrafish Information Network

Gene name: uchl3
Affected structure: neuron
Phenotype tag: abnormal
Phenotype quality: hyperplastic

Gene ontology

Biological process: ubiquitin-dependent protein catabolic process;protein deubiquitination;protein catabolic process;post-translational protein modification
Cellular component: nucleus;cytoplasm;cytosol
Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;peptidase activity;NEDD8-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity;ubiquitin binding