USP20

Summary

USP20 (ubiquitin specific peptidase 20, HGNC:12619) is a protein-coding gene on chromosome 9q34.11, encoding Ubiquitin carboxyl-terminal hydrolase 20 (Q9Y2K6). Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis.

This gene encodes a ubiquitin specific processing protease that was first identified as a substrate of the VHL (von Hippel-Lindau disease) protein E3 ubiquitin ligase complex. In addition to being ubiquitinated by the VHL-E3 ligase complex, this enzyme deubiquitinates hypoxia-inducible factor (HIF)-1 alpha and thereby causes increased expression of HIF-1alpha targeted genes which play a role in angiogenesis, glucose metabolism, cell proliferation and metastasis. The enzyme encoded by this gene also regulates G-protein coupled receptor signaling by mediating the deubiquitination of beta-2 adrenergic receptor (ADRB2). This enzyme is a ubiquitously expressed thiolester hydrolase. Alternative splicing results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 10868 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 198 total
• Druggable target: yes
• MANE Select transcript: NM_001110303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12619
Approved symbol	USP20
Name	ubiquitin specific peptidase 20
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1003
Ensembl gene	ENSG00000136878
Ensembl biotype	protein_coding
OMIM	615143
Entrez	10868

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 26 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000315480, ENST00000358355, ENST00000372429, ENST00000472108, ENST00000474895, ENST00000491053, ENST00000491731, ENST00000494971, ENST00000496927, ENST00000853423, ENST00000853424, ENST00000853425, ENST00000853426, ENST00000853427, ENST00000853428, ENST00000922133, ENST00000922134, ENST00000922135, ENST00000922136, ENST00000949808, ENST00000949809, ENST00000949810, ENST00000949811, ENST00000949812, ENST00000949813, ENST00000949814, ENST00000949815, ENST00000949816, ENST00000949817, ENST00000949818, ENST00000949819, ENST00000949820

RefSeq mRNA: 3 — MANE Select: NM_001110303 NM_001008563, NM_001110303, NM_006676

CCDS: CCDS43892

Canonical transcript exons

ENST00000372429 — 26 exons

Exon	Start	End
ENSE00000927297	129858467	129858598
ENSE00000927298	129860937	129861033
ENSE00000927299	129861543	129861612
ENSE00000927300	129863186	129863299
ENSE00000927301	129865303	129865381
ENSE00000927302	129868005	129868449
ENSE00000927305	129869672	129869844
ENSE00000927306	129870453	129870547
ENSE00000927307	129873482	129873515
ENSE00000927308	129873699	129873744
ENSE00000927309	129874576	129874756
ENSE00001364237	129849813	129849924
ENSE00001431684	129880467	129881828
ENSE00001816534	129835458	129835499
ENSE00003500392	129875310	129875479
ENSE00003500439	129858050	129858112
ENSE00003525803	129856307	129856360
ENSE00003534088	129876130	129876238
ENSE00003556754	129880113	129880289
ENSE00003557872	129878338	129878440
ENSE00003566148	129875560	129875641
ENSE00003593438	129852540	129852636
ENSE00003601282	129869310	129869425
ENSE00003602103	129874829	129874955
ENSE00003666047	129879573	129879644
ENSE00003668125	129868862	129869002

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 94.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7717 / max 235.8793, expressed in 1787 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98962	13.0223	1767
98961	2.0131	1189
98963	0.8376	426
98971	0.5320	84
98970	0.2718	75
98972	0.0950	45

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.81	gold quality
adenohypophysis	UBERON:0002196	94.22	gold quality
right lobe of thyroid gland	UBERON:0001119	93.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.21	gold quality
left lobe of thyroid gland	UBERON:0001120	92.80	gold quality
pituitary gland	UBERON:0000007	92.50	gold quality
cerebellar hemisphere	UBERON:0002245	92.47	gold quality
cerebellar cortex	UBERON:0002129	92.22	gold quality
right frontal lobe	UBERON:0002810	92.15	gold quality
thyroid gland	UBERON:0002046	91.56	gold quality
ascending aorta	UBERON:0001496	91.41	gold quality
thoracic aorta	UBERON:0001515	91.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.19	gold quality
lower esophagus	UBERON:0013473	91.17	gold quality
mucosa of stomach	UBERON:0001199	90.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.39	gold quality
descending thoracic aorta	UBERON:0002345	90.30	gold quality
aorta	UBERON:0000947	90.05	gold quality
cerebellum	UBERON:0002037	89.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.87	gold quality
lower esophagus mucosa	UBERON:0035834	89.78	gold quality
left adrenal gland cortex	UBERON:0035825	89.77	gold quality
left ovary	UBERON:0002119	89.61	gold quality
right ovary	UBERON:0002118	89.59	gold quality
cortical plate	UBERON:0005343	89.54	gold quality
spleen	UBERON:0002106	89.39	gold quality
popliteal artery	UBERON:0002250	89.24	gold quality
tibial artery	UBERON:0007610	89.23	gold quality
nucleus accumbens	UBERON:0001882	89.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	142.15
E-ANND-3	no	3.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting USP20, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-7113-5P	97.88	67.33	1735

Literature-anchored findings (GeneRIF, showing 17)

• identification and description of VDU2 in human cells (PMID:12865408)
• von Hippel-Lindau protein-interacting deubiquitinating enzyme 2 (VDU2) deubiquitinates and stabilizes HIF-1alpha. (PMID:15776016)
• USPs 20 and 33 serve as novel regulators that dictate both post-endocytic sorting as well as the intensity and extent of beta(2)AR signalling from the cell surface. (PMID:19424180)
• Our results point to USP20 as a key negative regulator of HTLV-1 Tax-induced NF-kappaB signaling. (PMID:21525354)
• Analysis of indel variations in the human disease-associated genes CDKN2AIP, WDR66, USP20 and OR7C2 in a Korean population. (PMID:22552337)
• data establish a new function of USP20 in genome maintenance and DNA repair. (PMID:24923443)
• findings reveal a dynamic regulation of USP20 by site-specific phosphorylation as well as the interdependence of signal transduction and trafficking pathways in balancing adrenergic stimulation and maintaining cellular homeostasis (PMID:25666616)
• we investigated the inter-action between PKM2 and USP20. Our results suggest a new molecular pathway in cancer metabolism through the regulation of PKM2. (PMID:25708858)
• USP20 regulates actin cytoskeleton organization and cell migration in a manner dependent on ERK3 expression. The results identify USP20 as a bona fide regulator of ERK3 stability and physiological functions. (PMID:28167606)
• our results demonstrate a role of the USP20 deubiquitinating enzyme in acting as a critical regulator of ULK1 and show a novel mechanism of the autophagy process in terms of ULK1 stability. (PMID:29487085)
• USP20 is a positive regulator of beta-catenin in cancer cell migration, invasion and tumor growth in vivo. Mechanistically, USP20 deubiquitinates and stabilizes beta-catenin and is a potential biomarker for predicting chemoresistance in cancer. (PMID:29867130)
• Study revealed the molecular basis for the weak binding of USP20 N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP) to mono-ubiquitin and poly-ubiquitin. The solution structure of USP20 ZnF-UBP domain consists of a central beta-sheet with either one alpha-helix or two alpha-helices packed on each side of the sheet. The overall structure of USP20 ZnF-UBP domain is stabilized by three coordinated zinc ions. (PMID:31278784)
• The Deubiquitinating Enzyme USP20 Regulates the TNFalpha-Induced NF-kappaB Signaling Pathway through Stabilization of p62. (PMID:32354117)
• Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2. (PMID:32943575)
• Expression, purification and characterization of the second DUSP domain of deubiquitinase USP20/VDU2. (PMID:33529762)
• Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins. (PMID:33792613)
• Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1beta-evoked signaling in vascular smooth muscle cells and vascular inflammation. (PMID:37311534)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp20	ENSDARG00000027501
mus_musculus	Usp20	ENSMUSG00000026854
rattus_norvegicus	Usp20	ENSRNOG00000007710

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242), USP32 (ENSG00000170832)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 20 — Q9Y2K6 (reviewed: Q9Y2K6)

Alternative names: Deubiquitinating enzyme 20, Ubiquitin thioesterase 20, Ubiquitin-specific-processing protease 20, VHL-interacting deubiquitinating enzyme 2

All UniProt accessions (1): Q9Y2K6

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis. Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination. Promotes cellular antiviral responses by deconjugating ‘Lys-33’ and ‘Lys-48’-linked ubiquitination of STING1 leading to its stabilization. Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1. Acts as a positive regulator for NF-kappa-B activation by TNF through deubiquitinating ‘Lys-48’-linked polyubiquitination of SQSTM1, leading to its increased stability. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity. Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability. Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol.

Subunit / interactions. Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with CCP110. Interacts with DIO2. Interacts with HIF1A. Interacts with ADRB2. Interacts with USP18.

Subcellular location. Cytoplasm. Endoplasmic reticulum. Perinuclear region. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.

Domain organisation. The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 55 is replaced by a Glu residue.

Similarity. Belongs to the peptidase C19 family. USP20/USP33 subfamily.

RefSeq proteins (3): NP_001008563, NP_001103773, NP_006667 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR001607	Znf_UBP	Domain
IPR006615	Pept_C19_DUSP	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR035927	DUSP-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050185	Ub_carboxyl-term_hydrolase	Family

Pfam: PF00443, PF02148, PF06337

UniProt features (52 total): binding site 12, modified residue 9, strand 5, turn 5, sequence conflict 4, domain 3, active site 2, sequence variant 2, mutagenesis site 2, helix 2, region of interest 2, compositionally biased region 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6KCZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2K6-F1	73.11	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 643 (proton acceptor); 154 (nucleophile)

Ligand- & substrate-binding residues (12): 8; 10; 30; 33; 43; 48; 53; 60; 64; 70; 83; 86

Post-translational modifications (9): 112, 132, 134, 258, 305, 368, 377, 408, 413

Mutagenesis-validated functional residues (2):

Position	Phenotype
154	abolishes deubiquitinating activity. does not inhibit lysosomal trafficking of adrb2; when associated with q-643.
643	abolishes deubiquitinating activity. does not inhibit lysosomal trafficking of adrb2; when associated with s-154.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 165 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, MORF_MSH3, MORF_BRCA1, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, MORF_RAD51L3, GOCC_MICROTUBULE_ORGANIZING_CENTER, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (11): proteolysis (GO:0006508), endocytosis (GO:0006897), nervous system development (GO:0007399), regulation of G protein-coupled receptor signaling pathway (GO:0008277), positive regulation of autophagy (GO:0010508), protein deubiquitination (GO:0016579), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), protein K63-linked deubiquitination (GO:0070536), protein K48-linked deubiquitination (GO:0071108), antiviral innate immune response (GO:0140374), canonical NF-kappaB signal transduction (GO:0007249)

GO Molecular Function (9): G protein-coupled receptor binding (GO:0001664), cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), zinc ion binding (GO:0008270), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
protein deubiquitination	2
cysteine-type peptidase activity	2
protein metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
system development	1
G protein-coupled receptor signaling pathway	1
regulation of signal transduction	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
innate immune response	1
defense response to virus	1
intracellular signaling cassette	1
signaling receptor binding	1
endopeptidase activity	1
deubiquitinase activity	1
transition metal ion binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP20	USP18	Q9UMW8	836
USP20	VHL	P40337	651
USP20	USP13	Q92995	643
USP20	USP5	P45974	634
USP20	ZUP1	Q96AP4	616
USP20	USP14	P54578	602
USP20	WSB1	Q9Y6I7	593
USP20	USP28	Q96RU2	592
USP20	TRAF6	Q9Y4K3	591
USP20	STAMBPL1	Q96FJ0	589
USP20	USP30	Q70CQ3	547
USP20	MYSM1	Q5VVJ2	547
USP20	ADRB2	P07550	542
USP20	STAMBP	O95630	542
USP20	USP29	Q9HBJ7	531

IntAct

260 interactions, top by confidence:

A	B	Type	Score
CBX7	BMI1	psi-mi:“MI:0914”(association)	0.940
USP20	VAPB	psi-mi:“MI:0915”(physical association)	0.850
USP20	VAPA	psi-mi:“MI:0915”(physical association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
IHO1	USP20	psi-mi:“MI:0915”(physical association)	0.720
BEND7	USP20	psi-mi:“MI:0915”(physical association)	0.720
USP20	FATE1	psi-mi:“MI:0915”(physical association)	0.720
USP20	MDFI	psi-mi:“MI:0915”(physical association)	0.720
MDFI	USP20	psi-mi:“MI:0915”(physical association)	0.720
USP20	IHO1	psi-mi:“MI:0915”(physical association)	0.720
USP20	BEND7	psi-mi:“MI:0915”(physical association)	0.720
FATE1	USP20	psi-mi:“MI:0915”(physical association)	0.720
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
SPRY2	USP20	psi-mi:“MI:0915”(physical association)	0.560
ALAS1	USP20	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	USP20	psi-mi:“MI:0915”(physical association)	0.560
USP20	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (288): PLA2G2A (Biochemical Activity), USP20 (Two-hybrid), USP20 (Two-hybrid), USP20 (Two-hybrid), USP20 (Two-hybrid), USP20 (Two-hybrid), USP20 (Two-hybrid), BEND5 (Two-hybrid), FATE1 (Two-hybrid), BEND7 (Two-hybrid), CCDC36 (Two-hybrid), USP20 (Affinity Capture-MS), USP20 (Affinity Capture-MS), USP20 (Affinity Capture-MS), USP20 (Biochemical Activity)

ESM2 similar proteins: A0JM59, A2BGT0, A5PJS6, A5PMR2, A5PN09, A6QNM7, A7Z056, B1AY15, B1WBD7, D2HBJ8, E1C213, E7F6T8, E9QG68, O88974, P52479, Q0V9G5, Q14694, Q15047, Q1RMU2, Q28CN3, Q2KJ09, Q2NL57, Q3KR59, Q5R5Z6, Q5RED8, Q5REG5, Q5XGZ2, Q5ZJN4, Q66H62, Q6NTR6, Q6P549, Q70CQ3, Q70CQ4, Q70EK9, Q7ZUM8, Q7ZXR7, Q80TQ2, Q8BW70, Q8C0R0, Q8C2S0

Diamond homologs: A0A0R4IB93, A0JM59, A1CIL1, A1CW53, A2XDG4, A3AF13, A5PN09, A6QNM7, A7Z056, B1WBD7, B2GUZ1, B8NSV5, D3ZJ96, F6Z5C0, O22207, O60079, O94966, Q0CT11, Q0E2F9, Q0VA64, Q13107, Q2HJE4, Q2UUG8, Q3UJD6, Q3V0C5, Q4VSI4, Q5I043, Q5R5Z6, Q5RCD3, Q5ZM45, Q60MK8, Q6A4J8, Q6J1Y9, Q6PAW2, Q6U7I1, Q6ZQ93, Q70CQ2, Q76LT8, Q7JKC3, Q84WU2

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
USP20	“up-regulates quantity by stabilization”	CLSPN	deubiquitination
ATR	“up-regulates quantity by stabilization”	USP20	phosphorylation
ATR	“down-regulates activity”	USP20	phosphorylation
HERC2	“down-regulates quantity”	USP20	ubiquitination
VCB-Cul2	“down-regulates quantity by destabilization”	USP20	polyubiquitination
HERC2	“down-regulates quantity by destabilization”	USP20	polyubiquitination
PRKACA	“down-regulates quantity by destabilization”	USP20	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

198 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4737 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129835145:T:TA	donor_gain	1.0000
9:129835152:AGT:A	donor_gain	1.0000
9:129835154:T:TA	donor_gain	1.0000
9:129835162:ATCTT:A	donor_gain	1.0000
9:129835163:T:C	donor_gain	1.0000
9:129835166:T:TA	donor_gain	1.0000
9:129858044:TCCCA:T	acceptor_loss	1.0000
9:129858045:CCCAG:C	acceptor_loss	1.0000
9:129858046:CCAG:C	acceptor_loss	1.0000
9:129858048:A:G	acceptor_loss	1.0000
9:129858111:AGG:A	donor_loss	1.0000
9:129858113:GT:G	donor_loss	1.0000
9:129858594:AACAG:A	donor_loss	1.0000
9:129858595:ACAGG:A	donor_loss	1.0000
9:129858597:AGGT:A	donor_loss	1.0000
9:129858598:GGT:G	donor_loss	1.0000
9:129858599:G:C	donor_loss	1.0000
9:129858600:T:G	donor_loss	1.0000
9:129860917:ACTTT:A	acceptor_gain	1.0000
9:129860922:G:A	acceptor_gain	1.0000
9:129860930:A:AG	acceptor_gain	1.0000
9:129860931:A:G	acceptor_gain	1.0000
9:129860933:A:AG	acceptor_gain	1.0000
9:129860933:ACAG:A	acceptor_gain	1.0000
9:129860934:C:G	acceptor_gain	1.0000
9:129861031:GAGGT:G	donor_loss	1.0000
9:129861033:GGT:G	donor_loss	1.0000
9:129861034:G:GA	donor_loss	1.0000
9:129861035:T:G	donor_loss	1.0000
9:129861529:T:TA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000044657 (9:129852201 G>A), RS1000167127 (9:129840374 T>A), RS1000221901 (9:129876757 G>T), RS1000260778 (9:129840628 T>C), RS1000273109 (9:129867376 C>G,T), RS1000364254 (9:129835001 G>A,C), RS1000444010 (9:129841838 G>A,C), RS1000495359 (9:129838955 G>T), RS1000581578 (9:129873362 G>A,C,T), RS1000628194 (9:129837618 G>A), RS1000633912 (9:129873082 T>G), RS1000641428 (9:129875704 G>C), RS1000696501 (9:129836376 A>T), RS1000741207 (9:129870756 C>G,T), RS1000742270 (9:129834042 C>T)

Disease associations

OMIM: gene MIM:615143 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1447	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010409	triacylglycerol 50:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3232682 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.80	IC50	160	nM	CHEMBL5723368

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	decreases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Genistein	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3239927	Binding	Inhibition of human USP20 using Ub-rhodamine 110 as substrate at 31 uM	X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1QY	HyCyte Huh-7 KO-hUSP20	Cancer cell line	Male
CVCL_TW72	HAP1 USP20 (-) 1	Cancer cell line	Male
CVCL_TW73	HAP1 USP20 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.