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.

• not_specified (23 variants)

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. These statistics are base on transcript: NM_000006002.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1			1
missense			23	1		24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4			4
Total	0	0	28	1	0

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
		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

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

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