USP36

protein-coding

ubiquitin specific peptidase 36, the group of Ubiquitin specific peptidases

Gene summary

This gene encodes a member of the peptidase C19 or ubiquitin-specific protease family of cysteine proteases. Members of this family remove ubiquitin molecules from polyubiquitinated proteins. The encoded protein may deubiquitinate and stabilize the transcription factor c-Myc, also known as MYC, an important oncoprotein known to be upregulated in most human cancers. The encoded protease may also regulate the activation of autophagy. This gene exhibits elevated expression in some breast and lung cancers. [provided by RefSeq, Mar 2016]

MANE transcript

NM_001385174.1

Inheritance

—

ClinVar variants

U:158B:35

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr17:78,787,381-78,841,441

External References & Databases

Ensembl (ENSG00000055483)

Transcript & Mutation Effects

hg38 • Region Span ~54.1 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 USP36 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 163

not providedTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001385174.1. 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			4 clinvar	8 clinvar	6 clinvar	18
missense			148 clinvar	17 clinvar	4 clinvar	169
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	158	25	10	193

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001385174.1	RefSeq	NP_001372103.1	18	MANE Select
ENST00000449938.7	Ensembl	ENSP00000401119.4	18	MANE Select
NM_001321291.2	RefSeq	NP_001308220.1	18	Standard
NM_001385169.1	RefSeq	NP_001372098.1	18	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
usp36	Danio rerio	Structure: pharyngeal arch cartilage Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

usp36

Danio rerio

Structure: pharyngeal arch cartilage

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process
nucleolus organization
negative regulation of macroautophagy
histone deubiquitination
protein deubiquitination

Molecular Function

RNA binding
cysteine-type endopeptidase activity
thiol-dependent ubiquitin-specific protease activity
protein binding

Cellular Component

nucleolus
cytoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000542802
Coding exons: 18
Length: 54061
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.398	720	691	1.04	0.0000425	7306
Missense (PolyPhen)		204	248.31	0.82155		2720
Synonymous	-1.40	316	286	1.11	0.0000193	2238
Loss of Function	4.35	18	51.8	0.347	0.00000278	576

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.000066	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Deubiquitinase essential for the regulation of nucleolar structure and function. Required for cell and organism viability. Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:29273634, PubMed:19208757, PubMed:22902402). Function as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.637
RVIS EVS: 2.11
RVIS percentile EVS: 97.9

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.885

Gene Damage Prediction

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