USP40

protein-coding

ubiquitin specific peptidase 40, the group of Ubiquitin specific peptidases

Gene summary

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP40 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001365479.2

Inheritance

—

ClinVar variants

U:200B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr2:233,475,526-233,566,782

External References & Databases

Ensembl (ENSG00000085982)

Transcript & Mutation Effects

hg38 • Region Span ~91.3 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 USP40 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 192

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365479.2. 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			3 clinvar	1 clinvar	2 clinvar	6
missense			188 clinvar	11 clinvar		199
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	200	12	2	214

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365479.2	RefSeq	NP_001352408.1	31	MANE Select
ENST00000678225.2	Ensembl	ENSP00000502952.1	31	MANE Select
NM_001382295.1	RefSeq	NP_001369224.1	31	Standard
NM_001382296.1	RefSeq	NP_001369225.1	32	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
usp40	Danio rerio	Structure: pronephric glomerular basement membrane Quality: decreased functionality abnormal

Gene / Model

Organism

Observed Phenotype

usp40

Danio rerio

Structure: pronephric glomerular basement membrane

Quality: decreased functionality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process
protein deubiquitination
regulation of protein stability

Molecular Function

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

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000450966
Coding exons: 31
Length: 91263
Individuals with no LoFs: 124400
Homozygous LoFs: 0
Heterozygous LoFs: 239
Defined: 124639
p: 0.000959

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.241	611	628	0.973	0.0000332	8145
Missense (PolyPhen)		195	201.11	0.9696		2719
Synonymous	0.325	223	229	0.973	0.0000130	2263
Loss of Function	2.06	49	67.2	0.729	0.00000324	880

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0052	0.0051	notable
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0012	0.0012	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00075	0.00069	rare
South Asian	0.00068	0.00065	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be catalytically inactive.;

Recessive Scores

pRec: 0.0910

Intolerance Scores

LoFtool: 0.986
RVIS EVS: 0.5
RVIS percentile EVS: 79.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.121

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High