USP54

protein-coding

ubiquitin specific peptidase 54, the group of Ubiquitin specific peptidases

Gene summary

Enables K63-linked deubiquitinase activity and cysteine-type deubiquitinase activity. Predicted to be involved in protein deubiquitination and proteolysis. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C10orf29

MANE transcript

NM_001391956.1

Inheritance

—

ClinVar variants

U:215B:13

Top phenotype

USP54-related disorder

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr10:73,497,538-73,626,117

External References & Databases

Ensembl (ENSG00000166348)

Transcript & Mutation Effects

hg38 • Region Span ~128.6 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 USP54 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 218

USP54-related disorderTotal: 4

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001391956.1. 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	1 clinvar		2
missense			209 clinvar	11 clinvar		220
nonsense			3 clinvar	1 clinvar		4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	215	13	0	228

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 101 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001391956.1	RefSeq	NP_001378885.1	22	MANE Select
ENST00000687698.1	Ensembl	ENSP00000510226.1	22	MANE Select
NM_001320437.2	RefSeq	NP_001307366.1	21	Standard
NM_001320441.2	RefSeq	NP_001307370.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein deubiquitination

Molecular Function

protein binding
thiol-dependent ubiquitinyl hydrolase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339859
Coding exons: 22
Length: 128416
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	729	910	0.801	0.0000477	11079
Missense (PolyPhen)		269	383.78	0.70091		4768
Synonymous	2.01	291	338	0.861	0.0000174	3281
Loss of Function	4.84	32	78.2	0.409	0.00000423	879

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00040	0.00033	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00026	0.00026	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has no peptidase activity.;

Intolerance Scores

LoFtool: 0.835
RVIS EVS: 1.06
RVIS percentile EVS: 91.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.221

Gene Damage Prediction

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