USP46

ubiquitin specific peptidase 46, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): 4:52590959-52659301

Links

ENSG00000109189 ∙ NCBI:64854 ∙ OMIM:612849 ∙ HGNC:20075 ∙ Uniprot:P62068 ∙ 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 USP46 gene.

• Inborn genetic diseases (6 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP46 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	2
missense			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	2

Variants in USP46

This is a list of pathogenic ClinVar variants found in the USP46 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-52598664-G-A			Benign (Feb 20, 2018)
4-52601870-C-T		not specified	Uncertain significance (Apr 13, 2022)
4-52601979-T-G		not specified	Uncertain significance (Feb 09, 2023)
4-52601980-C-T		not specified	Uncertain significance (Feb 28, 2023)
4-52628039-G-A		not specified	Uncertain significance (Nov 12, 2021)
4-52628048-G-A		not specified	Uncertain significance (Jul 14, 2021)
4-52628103-G-A		not specified	Uncertain significance (Aug 30, 2022)
4-52628116-G-A			Benign (Feb 20, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP46	protein_coding	protein_coding	ENST00000441222	9	68365

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.791	0.209	124698	0	5	124703	0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.87	85	199	0.428	0.0000109	2437
Missense in Polyphen		10	50.175	0.1993		678
Synonymous	1.75	55	74.1	0.742	0.00000416	630
Loss of Function	3.32	3	18.3	0.164	8.41e-7	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000129	0.000129
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67 (By similarity). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:19075014, PubMed:26388029). Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014). {ECO:0000250|UniProtKB:P62069, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:26388029}.
• Pathway: Circadian Clock;Mitochondrial biogenesis;NR1D1 (REV-ERBA) represses gene expression;Circadian Clock (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.506
• hipred: Y
• hipred_score: 0.783
• ghis: 0.679

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.782

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp46
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: behavioral fear response;ubiquitin-dependent protein catabolic process;adult feeding behavior;protein deubiquitination;regulation of synaptic transmission, GABAergic;behavioral response to ethanol;righting reflex;regulation of postsynaptic neurotransmitter receptor internalization
• Cellular component: glutamatergic synapse
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;thiol-dependent ubiquitinyl hydrolase activity;metal ion binding