USP38

protein-coding

ubiquitin specific peptidase 38, the group of Ubiquitin specific peptidases

Gene summary

Enables cysteine-type deubiquitinase activity. Involved in negative regulation of innate immune response; negative regulation of proteasomal ubiquitin-dependent protein catabolic process; and protein K33-linked deubiquitination. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_032557.6

Inheritance

—

ClinVar variants

U:133B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr4:143,184,917-143,225,212

External References & Databases

Ensembl (ENSG00000170185)

Transcript & Mutation Effects

hg38 • Region Span ~40.3 kb

Loading mutation effect viewer...

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 USP38 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 133

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032557.6. 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			2 clinvar			2
missense			129 clinvar	8 clinvar		137
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	133	8	0	141

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032557.6	RefSeq	NP_115946.2	10	MANE Select
ENST00000307017.9	Ensembl	ENSP00000303434.4	10	MANE Select
NM_001290325.1	RefSeq	NP_001277254.1	9	Standard
NM_001290326.1	RefSeq	NP_001277255.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrated Breast Cancer Pathway

Biological Process

ubiquitin-dependent protein catabolic process
protein deubiquitination

Molecular Function

cysteine-type endopeptidase activity
thiol-dependent ubiquitin-specific protease activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307017
Coding exons: 10
Length: 38914
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 58
Defined: 125748
p: 0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	471	539	0.874	0.0000253	6795
Missense (PolyPhen)		100	170.71	0.58579		2208
Synonymous	0.0835	208	210	0.993	0.0000102	2093
Loss of Function	3.37	18	41.4	0.435	0.00000200	517

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00019	0.00017	rare
Ashkenazi Jewish	0.0023	0.0021	notable
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.000092	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00021	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Deubiquitinating enzyme exhibiting a preference towards 'Lys-63'-linked ubiquitin chains. {ECO:0000269|PubMed:22689415}.;

Recessive Scores

pRec: 0.0968

Intolerance Scores

LoFtool: 0.685
RVIS EVS: -1.26
RVIS percentile EVS: 5.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.716

Gene Damage Prediction

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