USP30

Summary

USP30 (ubiquitin specific peptidase 30, HGNC:20065) is a protein-coding gene on chromosome 12q24.11, encoding Ubiquitin carboxyl-terminal hydrolase 30 (Q70CQ3). Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin’s abil….

USP30, a member of the ubiquitin-specific protease family (see USP1, MIM 603478), is a novel mitochondrial deubiquitinating (DUB) enzyme (Nakamura and Hirose, 2008 [PubMed 18287522]).

Source: NCBI Gene 84749 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 89 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_032663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20065
Approved symbol	USP30
Name	ubiquitin specific peptidase 30
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC10702, FLJ40511
Ensembl gene	ENSG00000135093
Ensembl biotype	protein_coding
OMIM	612492
Entrez	84749

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000257548, ENST00000377883, ENST00000392784, ENST00000467307, ENST00000470117, ENST00000479219, ENST00000491362, ENST00000536393, ENST00000536723, ENST00000539121, ENST00000910054, ENST00000910055, ENST00000910056, ENST00000910057, ENST00000910058, ENST00000928065, ENST00000928066, ENST00000928067, ENST00000962121, ENST00000962122

RefSeq mRNA: 2 — MANE Select: NM_032663 NM_001301175, NM_032663

CCDS: CCDS76599, CCDS9123

Canonical transcript exons

ENST00000257548 — 13 exons

Exon	Start	End
ENSE00000917910	109057926	109058108
ENSE00001513107	109085667	109088023
ENSE00001821890	109052576	109052761
ENSE00003462131	109082843	109083062
ENSE00003476156	109084953	109085073
ENSE00003554939	109081933	109082019
ENSE00003571752	109073438	109073532
ENSE00003577492	109082663	109082743
ENSE00003593786	109081334	109081393
ENSE00003612552	109071612	109071710
ENSE00003618707	109056682	109056791
ENSE00003677458	109067524	109067627
ENSE00003789781	109072305	109072350

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 94.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4705 / max 110.0576, expressed in 1789 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127909	11.4494	1789
127911	0.0211	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	94.53	gold quality
sperm	CL:0000019	92.10	gold quality
secondary oocyte	CL:0000655	90.86	gold quality
upper arm skin	UBERON:0004263	90.55	gold quality
oocyte	CL:0000023	90.26	gold quality
pigmented layer of retina	UBERON:0001782	90.25	gold quality
retina	UBERON:0000966	90.23	gold quality
corpus callosum	UBERON:0002336	90.02	gold quality
inferior vagus X ganglion	UBERON:0005363	90.01	gold quality
endothelial cell	CL:0000115	89.94	gold quality
left ventricle myocardium	UBERON:0006566	89.39	silver quality
lateral globus pallidus	UBERON:0002476	89.16	gold quality
subthalamic nucleus	UBERON:0001906	89.08	gold quality
cerebellar vermis	UBERON:0004720	88.81	gold quality
quadriceps femoris	UBERON:0001377	88.35	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.25	gold quality
medulla oblongata	UBERON:0001896	88.07	gold quality
vastus lateralis	UBERON:0001379	87.99	gold quality
superior vestibular nucleus	UBERON:0007227	87.86	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.81	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.58	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.40	gold quality
deltoid	UBERON:0001476	87.17	gold quality
biceps brachii	UBERON:0001507	87.10	gold quality
postcentral gyrus	UBERON:0002581	86.99	gold quality
ventral tegmental area	UBERON:0002691	86.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.79	gold quality
parietal lobe	UBERON:0001872	86.77	gold quality
substantia nigra pars compacta	UBERON:0001965	86.63	gold quality
tibialis anterior	UBERON:0001385	86.59	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting USP30, 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-4533	100.00	69.48	2758
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-5093	99.67	69.26	2291

Literature-anchored findings (GeneRIF, showing 16)

• USP30 participates in the maintenance of mitochondrial morphology, a finding that provides new insight into the cellular function of deubiquitination. (PMID:18287522)
• reducing USP30 activity enhances mitochondrial degradation in neurons (PMID:24896179)
• The mechanism by which parkin, an E3 ubiquitin ligase, and USP30, a mitochondrion-localized deubiquitylase, regulate mitophagy, was investigated. (PMID:25621951)
• These results provide the first evidence for a fundamental role of USP30 in determining the threshold for mitochondrial cell death and suggest USP30 as a potential target for combinatorial anti-cancer therapy. (PMID:25739811)
• show that USP30 delays mitophagy by delaying PARK2 recruitment to the mitochondria during mitophagy (PMID:25915564)
• Here the authors report crystal structures of human USP30 bound to monoubiquitin and Lys6-linked diubiquitin, which explain how USP30 achieves Lys6-linkage preference through unique ubiquitin binding interfaces. (PMID:28945249)
• the role of USP30 in the dynamic networks of mitochondrial quality control and its physiological implications. (PMID:29178074)
• we use two distinct mitophagy reporter systems to reveal tonic suppression by USP30, of a PINK1-dependent component of basal mitophagy in cells lacking detectable Parkin. (PMID:29895712)
• GNPAT and USP30-mediated stabilization of DRP1 play a critical role in the development of hepatocellular carcinoma (PMID:30143522)
• USP30 can rescue the peroxisome loss observed in some disease-causing peroxisome mutations, pointing to a potential therapeutic target. (PMID:30700497)
• Define the primary specificity of endogenous Parkin action on mitochondria, the abundance of ubiquitin proteoforms, the role of p97 in remodeling the mitochondrial proteome downstream of Parkin, and the target specificity of USP30 during mitophagic signaling. (PMID:32142685)
• The IKKbeta-USP30-ACLY Axis Controls Lipogenesis and Tumorigenesis. (PMID:32221968)
• Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues. (PMID:32484330)
• USP30 sets a trigger threshold for PINK1-PARKIN amplification of mitochondrial ubiquitylation. (PMID:32636217)
• LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A. (PMID:34694569)
• USP30 inhibition protects dopaminergic neurons. (PMID:38040789)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp30	ENSDARG00000056842
		ENSDARG00000104175
mus_musculus	Usp30	ENSMUSG00000029592
rattus_norvegicus	Usp30	ENSRNOG00000028556
drosophila_melanogaster	Usp30	FBGN0029819

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), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), 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 30 — Q70CQ3 (reviewed: Q70CQ3)

Alternative names: Deubiquitinating enzyme 30, Ubiquitin thioesterase 30, Ubiquitin-specific-processing protease 30

All UniProt accessions (7): B3KUS5, Q70CQ3, F5GXG2, F5H3L3, F5H8D3, S4R354, S4R3D1

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin’s ability to drive mitophagy. Preferentially cleaves ‘Lys-6’- and ‘Lys-11’-linked polyubiquitin chains, 2 types of linkage that participate in mitophagic signaling. Does not cleave efficiently polyubiquitin phosphorylated at ‘Ser-65’. Acts as a negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Expressed in skeletal muscle, pancreas, liver and kidney.

Post-translational modifications. Ubiquitinated by parkin (PRKN) at Lys-235 and Lys-289, leading to its degradation.

Activity regulation. Inhibited by the diterpenoid derivative 15-oxospiramilactone (S3).

Similarity. Belongs to the peptidase C19 family.

RefSeq proteins (2): NP_001288104, NP_116052* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443

UniProt features (46 total): strand 20, helix 9, mutagenesis site 5, topological domain 2, active site 2, cross-link 2, chain 1, sequence variant 1, transmembrane region 1, turn 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9F6G	X-RAY DIFFRACTION	1.5
5OHK	X-RAY DIFFRACTION	2.34
9LYF	X-RAY DIFFRACTION	2.58
9F19	X-RAY DIFFRACTION	2.75
5OHP	X-RAY DIFFRACTION	2.8
8D1T	X-RAY DIFFRACTION	2.94
8D0A	X-RAY DIFFRACTION	3.19
5OHN	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70CQ3-F1	77.29	0.51

Antibody-complex structures (SAbDab): 2 — 8D0A, 8D1T

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): 77 (nucleophile); 452 (proton acceptor)

Post-translational modifications (2): 235, 289

Mutagenesis-validated functional residues (5):

Position	Phenotype
28	no change in mitochondrial subcellular location; when associated with n-30 and n-33.
30	no effect on subcellular location; when associated with n-28 and n-33.
33	no effect on subcellular location; when associated with n-28 and n-30.
59–64	loss of mitochondrial subcellular location. located in the endoplasmic reticulum.
77	loss of deubiquitinase activity and impaired ability to inhibit mitophagy. increased tomm20 ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases
R-HSA-9664873	Pexophagy

MSigDB gene sets: 174 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_MACROAUTOPHAGY, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, MODULE_171, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, CYTAGCAAY_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_MACROAUTOPHAGY, GOBP_MITOCHONDRIAL_FUSION, GOCC_MICROBODY_MEMBRANE

GO Biological Process (9): autophagy of mitochondrion (GO:0000422), pexophagy (GO:0000425), proteolysis (GO:0006508), mitochondrial fusion (GO:0008053), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), protein K11-linked deubiquitination (GO:0035871), protein K6-linked deubiquitination (GO:0044313), negative regulation of mitophagy (GO:1901525)

GO Molecular Function (7): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), deubiquitinase activity (GO:0101005), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Deubiquitination	1
Selective autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein deubiquitination	2
cysteine-type peptidase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
autophagy	1
macroautophagy	1
autophagy of peroxisome	1
protein metabolic process	1
mitochondrion organization	1
organelle fusion	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
mitophagy	1
negative regulation of macroautophagy	1
regulation of mitophagy	1
negative regulation of autophagy of mitochondrion	1
endopeptidase activity	1
deubiquitinase activity	1
ubiquitin-like protein peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
mitochondrial membrane	1
organelle outer membrane	1
peroxisome	1
microbody membrane	1

Protein interactions and networks

STRING

1633 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP30	ZUP1	Q96AP4	925
USP30	FIS1	Q9Y3D6	914
USP30	USP1	O94782	875
USP30	PINK1	Q9BXM7	806
USP30	USP35	Q9P2H5	761
USP30	USP5	P45974	700
USP30	USP14	P54578	666
USP30	PRKN	O60260	658
USP30	MUL1	Q969V5	654
USP30	MARCHF5	Q9NX47	651
USP30	USP13	Q92995	643
USP30	USP7	Q93009	642
USP30	GNPAT	O15228	636
USP30	TOMM20	Q15388	635
USP30	PARL	Q9H300	619

IntAct

86 interactions, top by confidence:

A	B	Type	Score
	USP30	psi-mi:“MI:0915”(physical association)	0.720
	USP30	psi-mi:“MI:0570”(protein cleavage)	0.720
	USP30	psi-mi:“MI:0407”(direct interaction)	0.720
USP30		psi-mi:“MI:0204”(deubiquitination reaction)	0.720
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
RHBDD2	USP30	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	USP30	psi-mi:“MI:0915”(physical association)	0.560
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
EXOSC7	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PACC1	DEGS1	psi-mi:“MI:0914”(association)	0.350
EXT2	ATE1	psi-mi:“MI:0914”(association)	0.350

BioGRID (167): USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), UBC (Biochemical Activity), USP30 (Synthetic Lethality), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS), USP30 (Affinity Capture-MS)

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: A2BGT0, A4QNN3, D3ZPG5, Q0VA64, Q3UN04, Q6PAW2, Q70CQ3, Q8W4N3, Q9FPT5, Q9P7S5, Q7JKC3, Q9UHP3, A5PN09, A6QNM7, A6QR55, A6ZY34, A7Z056, A8HAL1, B1WBD7, B2GUX4, B2GUZ1, B3LGK1, D2HBJ8, E2RK09, E9QG68, F1SRY5, F6Z5C0, F8VPU6, F8VPZ3, M9PD06, O13747, O57429, O75604, O80996, O88623, O94269, P32571, P35125, P38748, P40453

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
miR‑137	“down-regulates quantity by destabilization”	USP30	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57157	GRCh38/hg38 12q23.3-24.13(chr12:105234677-112194686)x1	Pathogenic

SpliceAI

1548 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109052758:TCAGG:T	donor_loss	1.0000
12:109052759:CAGG:C	donor_loss	1.0000
12:109052760:AGGTG:A	donor_loss	1.0000
12:109052761:GGTG:G	donor_loss	1.0000
12:109052762:G:GC	donor_loss	1.0000
12:109052763:T:A	donor_loss	1.0000
12:109056680:A:AG	acceptor_gain	1.0000
12:109056681:G:GG	acceptor_gain	1.0000
12:109056787:AAAAG:A	donor_loss	1.0000
12:109056788:AAAG:A	donor_loss	1.0000
12:109056789:AAGGT:A	donor_loss	1.0000
12:109056791:GGTAA:G	donor_loss	1.0000
12:109056792:G:GC	donor_loss	1.0000
12:109056793:T:A	donor_loss	1.0000
12:109058074:G:GG	donor_gain	1.0000
12:109067515:T:TA	acceptor_gain	1.0000
12:109067519:TCCA:T	acceptor_loss	1.0000
12:109067521:CA:C	acceptor_loss	1.0000
12:109067522:A:AG	acceptor_gain	1.0000
12:109067522:A:T	acceptor_loss	1.0000
12:109067523:G:GA	acceptor_gain	1.0000
12:109067523:GC:G	acceptor_gain	1.0000
12:109067523:GCC:G	acceptor_gain	1.0000
12:109067523:GCCT:G	acceptor_gain	1.0000
12:109067523:GCCTT:G	acceptor_gain	1.0000
12:109067625:CAGG:C	donor_loss	1.0000
12:109067628:G:GG	donor_gain	1.0000
12:109067628:GT:G	donor_loss	1.0000
12:109081931:AG:A	acceptor_gain	1.0000
12:109081932:GG:G	acceptor_gain	1.0000

AlphaMissense

3373 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:109056714:G:A	G39D	1.000
12:109056723:C:A	A42D	1.000
12:109056726:C:A	A43D	1.000
12:109056729:C:A	A44D	1.000
12:109057938:G:A	G69D	1.000
12:109057941:T:A	L70H	1.000
12:109057941:T:C	L70P	1.000
12:109057946:A:G	N72D	1.000
12:109057948:T:A	N72K	1.000
12:109057948:T:G	N72K	1.000
12:109057961:T:C	C77R	1.000
12:109057962:G:A	C77Y	1.000
12:109057963:C:G	C77W	1.000
12:109057964:T:A	F78I	1.000
12:109057964:T:C	F78L	1.000
12:109057965:T:C	F78S	1.000
12:109057966:C:A	F78L	1.000
12:109057966:C:G	F78L	1.000
12:109057972:C:A	N80K	1.000
12:109057972:C:G	N80K	1.000
12:109057985:G:C	G85R	1.000
12:109071612:G:C	D161H	1.000
12:109071613:A:C	D161A	1.000
12:109071613:A:G	D161G	1.000
12:109071613:A:T	D161V	1.000
12:109071614:T:A	D161E	1.000
12:109071614:T:G	D161E	1.000
12:109071621:G:A	E164K	1.000
12:109071622:A:T	E164V	1.000
12:109071623:A:C	E164D	1.000

dbSNP variants (sampled 300 via entrez): RS1000006574 (12:109073201 A>G), RS1000080640 (12:109028568 A>C,G), RS1000132937 (12:109028865 A>G), RS1000230176 (12:109025479 T>A), RS1000274428 (12:109038289 C>A), RS1000361393 (12:109023282 A>G), RS1000411724 (12:109060631 C>A,T), RS1000535258 (12:109026490 G>T), RS1000558042 (12:109048353 C>T), RS1000679639 (12:109054452 T>G), RS1000830792 (12:109062389 C>T), RS1000843980 (12:109035337 A>T), RS1000886994 (12:109060841 G>A), RS1000902151 (12:109081164 A>G), RS1000930107 (12:109048018 T>C)

Disease associations

OMIM: gene MIM:612492 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004603_113	Platelet count	7.000000e-32
GCST004607_51	Plateletcrit	6.000000e-40
GCST90002400_724	Plateletcrit	5.000000e-120
GCST90002402_145	Platelet count	1.000000e-92

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523357 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

894 measured of 1119 human assays (1119 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-chloro-N-[(2R)-8-cyano-8-azabicyclo[3.2.1]octan-2-yl]-4-(4-methylpyrazol-1-yl)benzamide	IC50	10 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-6-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-N,9-dimethyl-1,2,3,4-tetrahydrocarbazole-3-carboxamide	IC50	17 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-6-chloro-N-((1R,2R,4S)-7-cyano-7- azabicyclo[2.2.1]heptan-2-yl)-2,3,4,9- tetrahydro-1H-carbazole-3-carboxamide	IC50	20 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
1-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-[2-(2,5-dichlorophenyl)ethyl]-1,3-dimethylurea	IC50	22 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-1-(3-chloro-5-methylphenyl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]pyrrolidine-3-carboxamide	IC50	25 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
cis-(1R,3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-(2,5-dichlorophenyl)cyclopentane-1-carboxamide	IC50	25 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
6-chloro-N-((1R,2R,4S)-7-cyano-7- azabicyclo[2.2.1]heptan-2-yl)-1-(6- (cyanomethyl)-2-pyridinyl)-1H-indazole-5- carboxamide	IC50	26 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(E)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-(2,5-dichlorophenyl)but-3-enamide	IC50	26 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[3-(cyanomethyl)-4-methylphenyl]benzamide	IC50	26 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[3-(1-cyanocyclopropyl)-5-fluorophenyl]benzamide	IC50	27 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[6-(1-cyanocyclopropyl)-2-pyridinyl]benzamide	IC50	27 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[3-(2-cyanopropan-2-yl)phenyl]benzamide	IC50	28 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-1-[3-chloro-6-(trifluoromethyl)-2-pyridinyl]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]pyrrolidine-3-carboxamide	IC50	29 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-1-[3-chloro-5-(trifluoromethyl)phenyl]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]pyrrolidine-3-carboxamide	IC50	29 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[3-(cyanomethyl)-5-methylphenyl]benzamide	IC50	30 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-((1R,2R,4S)-7-cyano-7- azabicyclo[2.2.1]heptan-2-yl)-4-((3R)-3- cyano-3-methyl-2,3-dihydro-1H-inden-5- yl)benzamide	IC50	31 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(E)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-(2,5-dichlorophenyl)-N-methylbut-3-enamide	IC50	34 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[6-(1-cyanocyclopropyl)-2-pyridinyl]-N-methylbenzamide	IC50	37 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(2,5-dichlorophenyl)pyrrolidine-3-carboxamide	IC50	37 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(E)-3-(5-chloro-1-benzothiophen-3-yl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-2-methylprop-2-enamide	IC50	38 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[6-(1-cyanocyclopropyl)-2-pyridinyl]-2-(trifluoromethyl)benzamide	IC50	39 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(E)-3-(5-chloro-1-ethylindol-3-yl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-2-methylprop-2-enamide	IC50	40 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[3-(1-cyanocyclopropyl)phenyl]benzamide	IC50	41 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
3-(3-bromophenyl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]benzamide	IC50	44 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-1-(3-chloro-5-cyanophenyl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]pyrrolidine-3-carboxamide	IC50	44 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-(3-cyano-3-methyl-1,2-dihydroinden-5-yl)benzamide	IC50	46 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(3,5-dichlorophenyl)pyrrolidine-3-carboxamide	IC50	46 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(1S,4R,5S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-2-(3,5-dichlorophenyl)-2-azabicyclo[3.1.0]hexane-4-carboxamide	IC50	48 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-4-[3-(1-cyanocyclobutyl)phenyl]benzamide	IC50	49 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-(2-methylbutoxy)-4-(1-methylpyrazol-4-yl)benzamide	IC50	50 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-(2-methylpropoxy)-4-(3-methylpyrazol-1-yl)benzamide	IC50	50 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(E)-4-(3-chlorophenyl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]but-3-enamide	IC50	54 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-1-(5-chloro-2-cyanophenyl)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]pyrrolidine-3-carboxamide	IC50	54 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(3,4,6-trichloro-2-pyridinyl)pyrrolidine-3-carboxamide	IC50	54 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-4-[3-chloro-5-(cyanomethyl)phenyl]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]benzamide	IC50	55 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-4-[4-chloro-3-(cyanomethyl)phenyl]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]benzamide	IC50	55 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-(4-fluorophenoxy)benzamide	IC50	56 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
6-[[1-(4-bromophenyl)cyclopropyl]methyl-methylamino]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]pyrimidine-4-carboxamide	IC50	57 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
6-chloro-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(6-cyano-2-pyridinyl)indazole-5-carboxamide	IC50	57 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-(2-methylpropoxy)-4-(1-methylpyrazol-3-yl)benzamide	IC50	58 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-[3-cyano-6-(trifluoromethyl)-2-pyridinyl]pyrrolidine-3-carboxamide	IC50	58 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-4-[2-chloro-3-(cyanomethyl)phenyl]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]benzamide	IC50	60 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
2-chloro-N-((1R,2R,4S)-7-cyano-7- azabicyclo[2.2.1]heptan-2-yl)-4-(6- cyclopropyl-2-pyridinyl)benzamide	IC50	61 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
3-chloro-N-((1R,2R,4S)-7-cyano-7- azabicyclo[2.2.1]heptan-2-yl)-3’-cyclopropyl- 5’-fluoro[biphenyl]-4-carboxamide	IC50	62 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(3,5-dichloro-4-fluorophenyl)pyrrolidine-3-carboxamide	IC50	62 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(1S,4S,5S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-2-(3,5-dichlorophenyl)-2-azabicyclo[3.1.0]hexane-4-carboxamide	IC50	62 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(6-cyclopropyl-2-pyridinyl)-6-fluoro-N-methylindazole-5-carboxamide	IC50	64 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-3-(2,5-dichlorophenyl)cyclopentane-1-carboxamide	IC50	64 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
(3S)-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]-1-(2,3-dichlorophenyl)pyrrolidine-3-carboxamide	IC50	64 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof
3-[(4-chlorophenyl)methyl]-N-[(1R,2R,4S)-7-cyano-7-azabicyclo[2.2.1]heptan-2-yl]benzamide	IC50	65 nM	US-11572374: N-cyano-7-azanorbornane derivatives and uses thereof

ChEMBL bioactivities

2256 potent at pChembl≥5 of 2282 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.26	IC50	0.55	nM	CHEMBL4466998
9.26	IC50	0.55	nM	CHEMBL4553219
9.26	IC50	0.55	nM	CHEMBL4449295
9.26	IC50	0.55	nM	CHEMBL4443079
9.26	IC50	0.55	nM	CHEMBL4553485
9.26	IC50	0.55	nM	CHEMBL4560355
9.26	IC50	0.55	nM	CHEMBL4573084
9.26	IC50	0.55	nM	CHEMBL4537641
9.26	IC50	0.55	nM	CHEMBL4459314
9.26	IC50	0.55	nM	CHEMBL4438257
9.26	IC50	0.55	nM	CHEMBL4463057
9.26	IC50	0.55	nM	CHEMBL4455077
9.26	IC50	0.55	nM	CHEMBL4525773
9.26	IC50	0.55	nM	CHEMBL4474438
9.26	IC50	0.55	nM	CHEMBL4445549
9.26	IC50	0.55	nM	CHEMBL4436246
9.26	IC50	0.55	nM	CHEMBL4574552
9.26	IC50	0.55	nM	CHEMBL4519999
9.26	IC50	0.55	nM	CHEMBL4467553
9.26	IC50	0.55	nM	CHEMBL4449473
9.26	IC50	0.55	nM	CHEMBL4562533
9.26	IC50	0.55	nM	CHEMBL4459967
9.26	IC50	0.55	nM	CHEMBL5755678
9.26	IC50	0.55	nM	CHEMBL4467679
9.26	IC50	0.55	nM	CHEMBL4451399
9.26	IC50	0.55	nM	CHEMBL4465362
9.26	IC50	0.55	nM	CHEMBL4449937
9.26	IC50	0.55	nM	CHEMBL4541414
9.26	IC50	0.55	nM	CHEMBL4436843
9.26	IC50	0.55	nM	CHEMBL4447536
9.26	IC50	0.55	nM	CHEMBL4569323
9.26	IC50	0.55	nM	CHEMBL4443544
9.26	IC50	0.55	nM	CHEMBL4543932
9.26	IC50	0.55	nM	CHEMBL4474816
9.26	IC50	0.55	nM	CHEMBL4446824
9.26	IC50	0.55	nM	CHEMBL4483009
9.26	IC50	0.55	nM	CHEMBL4517672
9.26	IC50	0.55	nM	CHEMBL4586482
9.18	IC50	0.66	nM	CHEMBL4437008
9.18	IC50	0.66	nM	CHEMBL4535538
9.18	IC50	0.66	nM	CHEMBL4468244
9.18	IC50	0.66	nM	CHEMBL4467909
9.18	IC50	0.66	nM	CHEMBL4530917
9.18	IC50	0.66	nM	CHEMBL4469717
9.18	IC50	0.66	nM	CHEMBL4561489
9.18	IC50	0.66	nM	CHEMBL4583715
9.18	IC50	0.66	nM	CHEMBL4564354
9.18	IC50	0.66	nM	CHEMBL4460715
9.18	IC50	0.66	nM	CHEMBL4545486
9.18	IC50	0.66	nM	CHEMBL4594138

PubChem BioAssay actives

34 with measured affinity, of 58 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(3-cyanophenyl)-N-[[(3R)-1-cyanopyrrolidin-3-yl]methyl]-1,2,4-triazole-3-carboxamide	1920334: Inhibition of USP30 (unknown origin)	ic50	0.0100	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-1-oxo-3-pyridin-4-ylpropan-2-yl]-4-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0200	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-1-oxo-3-thiophen-2-ylpropan-2-yl]-4-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0200	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-1-oxo-3-phenylpropan-2-yl]-4-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0200	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]-4-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0200	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]-3,4-difluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0300	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-1-oxo-3-thiophen-2-ylpropan-2-yl]cyclohexanecarboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0300	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0490	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-1-oxo-3-phenylpropan-2-yl]cyclohexanecarboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0600	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]-3-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0600	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]cyclohexanecarboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0800	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.0900	uM
(2S)-1-cyano-N-[4-(3-cyanophenyl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide	1679973: Inhibition of USP30 (unknown origin)	ic50	0.1000	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4,4-difluorocyclohexane-1-carboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.1000	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]cyclohexanecarboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.1200	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]pyridine-2-carboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.1200	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]pyridine-2-carboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.1600	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-1,3-thiazole-2-carboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.1800	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.2300	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-1-oxo-3-phenylpropan-2-yl]pyridine-2-carboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.2500	uM
N-[(2R)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.2500	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4-cyanobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.2700	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.2700	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]cyclopentanecarboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.3700	uM
N-[1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1679973: Inhibition of USP30 (unknown origin)	ic50	0.3700	uM
N-[(2S)-1-[4-(tert-butylsulfamoyl)anilino]-3-cyclohexyl-1-oxopropan-2-yl]-2-fluorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.4600	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.4700	uM
N-[1-oxo-3-phenyl-1-[[5-(propan-2-ylsulfamoyl)naphthalen-1-yl]amino]propan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.5100	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.6700	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4-chlorobenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	0.8300	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-4-phenylbutan-2-yl]benzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	2.2700	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4-methylbenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	2.5000	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]cycloheptanecarboxamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	4.3000	uM
N-[(2S)-1-[[5-(tert-butylsulfamoyl)naphthalen-1-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4-methoxybenzamide	1679977: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay	ic50	9.0000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression	4
Benzo(a)pyrene	decreases expression, increases methylation	3
Acetaminophen	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
deoxynivalenol	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
manganese chloride	decreases expression, increases abundance	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects expression, decreases reaction	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
Anisomycin	increases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1

ChEMBL screening assays

35 unique, capped per target: 34 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418408	Binding	Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by flu	1-cyano-pyrrolidine compounds as usp30 inhibitors
CHEMBL5723320	Functional	Affinity Biochemical interaction: (Fluorescence polarisation assay) EUB0002794a USP30	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2NM	HAP1 USP30 (-) 3	Cancer cell line	Male
CVCL_E2NN	HAP1 USP30 (-) 4	Cancer cell line	Male
CVCL_TW84	HAP1 USP30 (-) 1	Cancer cell line	Male
CVCL_TW85	HAP1 USP30 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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