USP3

protein-coding

ubiquitin specific peptidase 3, the group of Ubiquitin specific peptidases

Gene summary

Enables deubiquitinase activity and histone binding activity. Involved in DNA repair and DNA repair-dependent chromatin remodeling. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006537.4

Inheritance

—

ClinVar variants

U:56B:3

Top phenotype

Decreased total neutrophil count

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr15:63,504,511-63,594,640

External References & Databases

Ensembl (ENSG00000140455)

Transcript & Mutation Effects

hg38 • Region Span ~90.1 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 USP3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 3

Decreased total neutrophil countTotal: 1

Decreased total lymphocyte countTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006537.4. 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			53 clinvar		1 clinvar	54
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	56	0	3	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006537.4	RefSeq	NP_006528.2	15	MANE Select
ENST00000380324.8	Ensembl	ENSP00000369681.3	15	MANE Select
NM_001256702.2	RefSeq	NP_001243631.1	14	Standard
ENST00000268049.11	Ensembl	ENSP00000268049.7	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
usp3	Danio rerio	Structure: caudal fin upper lobe Quality: fused with abnormal

Gene / Model

Organism

Observed Phenotype

usp3

Danio rerio

Structure: caudal fin upper lobe

Quality: fused with

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Ub-specific processing proteases
Deubiquitination

Biological Process

negative regulation of transcription by RNA polymerase II
mitotic cell cycle
DNA repair
ubiquitin-dependent protein catabolic process
histone deubiquitination

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
thiol-dependent ubiquitin-specific protease activity
zinc ion binding
thiol-dependent ubiquitinyl hydrolase activity
histone binding

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
cytoplasm
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380324
Coding exons: 15
Length: 90047
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125747
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.11	184	284	0.648	0.0000152	3432
Missense (PolyPhen)		60	126.24	0.47528		1560
Synonymous	-0.462	112	106	1.06	0.00000615	918
Loss of Function	4.94	1	30.3	0.0330	0.00000137	402

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000063	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolase that deubiquitinates monoubiquitinated target proteins such as histone H2A and H2B. Required for proper progression through S phase and subsequent mitotic entry. May regulate the DNA damage response (DDR) checkpoint through deubiquitination of H2A at DNA damage sites. Associates with the chromatin. {ECO:0000269|PubMed:17980597}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.316
RVIS EVS: -0.43
RVIS percentile EVS: 25.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.924

Gene Damage Prediction

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