USP50

protein-coding

ubiquitin specific peptidase 50, the group of Ubiquitin specific peptidases

Gene summary

Enables cysteine-type deubiquitinase activity. Involved in regulation of cell cycle G2/M phase transition. Acts upstream of or within several processes, including nuclear speck organization; positive regulation of NLRP3 inflammasome complex assembly; and positive regulation of interleukin-1 beta production. Located in centrosome; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_203494.5

Inheritance

—

ClinVar variants

U:52B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.4

Max pathogenic AF

—

Genomic locus

chr15:50,494,018-50,546,708

External References & Databases

Ensembl (ENSG00000170236)

Transcript & Mutation Effects

hg38 • Region Span ~52.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to USP50 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_203494.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			51 clinvar	3 clinvar		54
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	0	0	52	3	3	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_203494.5	RefSeq	NP_987090.2	7	MANE Select
ENST00000532404.6	Ensembl	ENSP00000434676.1	7	MANE Select
ENST00000529349.2	Ensembl	ENSP00000434014.2	2	Standard
ENST00000559105.5	Ensembl	ENSP00000453946.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process
endosome organization
Ras protein signal transduction
protein deubiquitination
positive regulation of protein homooligomerization

Molecular Function

thiol-dependent ubiquitin-specific protease activity
ubiquitin-like protein-specific protease activity

Cellular Component

cytosol
postsynaptic density
extrinsic component of plasma membrane
midbody
extrinsic component of endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000532404
Coding exons: 7
Length: 46147
Individuals with no LoFs: 123408
Homozygous LoFs: 24
Heterozygous LoFs: 1210
Defined: 124642
p: 0.00496

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.390	165	180	0.918	0.00000922	2194
Missense (PolyPhen)		41	56.303	0.7282		753
Synonymous	0.190	67	69.0	0.971	0.00000397	605
Loss of Function	-1.52	23	16.4	1.40	6.87e-7	216

Population LoF Frequency

Population	CAF	p-value	Status
African	0.057	0.057	notable
Latino/Admixed American	0.0024	0.0024	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0012	0.0012	notable
Finnish	0.00088	0.00088	rare
European (Non-Finnish)	0.00071	0.00071	rare
South Asian	0.0051	0.0050	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has no peptidase activity.;

Recessive Scores

pRec: 0.0994

Intolerance Scores

LoFtool: 0.744
RVIS EVS: 0.4
RVIS percentile EVS: 76.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.364

Gene Damage Prediction

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