THOP1

Summary

THOP1 (thimet oligopeptidase 1, HGNC:11793) is a protein-coding gene on chromosome 19p13.3, encoding Thimet oligopeptidase (P52888). Involved in the metabolism of neuropeptides under 20 amino acid residues long.

The protein encoded by this gene is a kininase that uses zinc as a cofactor. The encoded oligopeptidase cleaves cytosolic peptides, making them unavailable for display on antigen-presenting cells. This protein also cleaves neuropeptides under 20 aa in length and can degrade beta-amyloid precursor protein to amyloidogenic peptides.

Source: NCBI Gene 7064 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 152 total
• Druggable target: yes
• MANE Select transcript: NM_003249

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11793
Approved symbol	THOP1
Name	thimet oligopeptidase 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172009
Ensembl biotype	protein_coding
OMIM	601117
Entrez	7064

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 23 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000307741, ENST00000395212, ENST00000585338, ENST00000585673, ENST00000586677, ENST00000586780, ENST00000587401, ENST00000587468, ENST00000589087, ENST00000590533, ENST00000590970, ENST00000591149, ENST00000591363, ENST00000592639, ENST00000877633, ENST00000877634, ENST00000877635, ENST00000917965, ENST00000917966, ENST00000917967, ENST00000917968, ENST00000917969, ENST00000917970, ENST00000917971, ENST00000917972, ENST00000917973, ENST00000917974, ENST00000950842, ENST00000950843, ENST00000950844, ENST00000950845, ENST00000950846

RefSeq mRNA: 1 — MANE Select: NM_003249 NM_003249

CCDS: CCDS12095

Canonical transcript exons

ENST00000307741 — 13 exons

Exon	Start	End
ENSE00001630589	2807442	2807808
ENSE00001652222	2805016	2805176
ENSE00001774446	2806917	2807052
ENSE00002829359	2785503	2785678
ENSE00002959316	2813115	2815807
ENSE00003462206	2796081	2796188
ENSE00003507776	2808243	2808444
ENSE00003532502	2810640	2810768
ENSE00003551554	2790421	2790633
ENSE00003589051	2811598	2811734
ENSE00003595418	2794764	2794912
ENSE00003613136	2810304	2810490
ENSE00003634789	2799689	2799791

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.7764 / max 173.7470, expressed in 1801 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173118	21.6784	1800
173119	0.0980	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.45	gold quality
right testis	UBERON:0004534	97.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.74	gold quality
right frontal lobe	UBERON:0002810	96.34	gold quality
cerebellar hemisphere	UBERON:0002245	96.09	gold quality
cerebellar cortex	UBERON:0002129	95.83	gold quality
ventricular zone	UBERON:0003053	95.26	gold quality
right lobe of liver	UBERON:0001114	94.98	gold quality
lower esophagus mucosa	UBERON:0035834	94.80	gold quality
apex of heart	UBERON:0002098	94.65	gold quality
adenohypophysis	UBERON:0002196	94.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.97	gold quality
mucosa of transverse colon	UBERON:0004991	93.73	gold quality
gastrocnemius	UBERON:0001388	93.44	gold quality
right atrium auricular region	UBERON:0006631	93.43	gold quality
prefrontal cortex	UBERON:0000451	93.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.32	gold quality
testis	UBERON:0000473	93.07	gold quality
cingulate cortex	UBERON:0003027	92.91	gold quality
muscle of leg	UBERON:0001383	92.74	gold quality
anterior cingulate cortex	UBERON:0009835	92.71	gold quality
ganglionic eminence	UBERON:0004023	92.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.58	gold quality
nucleus accumbens	UBERON:0001882	92.57	gold quality
caudate nucleus	UBERON:0001873	92.40	gold quality
cerebellum	UBERON:0002037	92.36	gold quality
amygdala	UBERON:0001876	92.03	gold quality
pituitary gland	UBERON:0000007	91.88	gold quality
right lobe of thyroid gland	UBERON:0001119	91.44	gold quality
esophagus mucosa	UBERON:0002469	91.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CREM, E2F4, ESR1, EZH2, HNF4A, NFAT5, NR4A2, SRY, TP63, TP73

miRNA regulators (miRDB)

17 targeting THOP1, 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-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-6863	93.93	67.77	154

Literature-anchored findings (GeneRIF, showing 15)

• human thimet oligopeptidase crystal structure shows substrate recognition, regulation, and localization (PMID:14998993)
• THIMET has a role in degradation of peptides generated by proteasomes (PMID:15328361)
• EP24.15 associates with AT1 and B2 receptors both at the plasma membrane and after receptor internalization (PMID:15376229)
• Mutations at only two residues (Glu-469 and Arg-498) are required to swap specificity with neurolysin, a result that is confirmed by testing the two-mutant constructs. (PMID:17251185)
• increase in THOP1 expression might be part of a compensatory defense mechanism of the brain against an increased Abeta load. (PMID:18571100)
• Over 100 peptides were identified in human embryonic kidney 293 (HEK293) cells that are derived from intracellular proteins; many but not all of these peptides are substrates or products of EP24.15. (PMID:19282285)
• interaction between EP24.15 and calmodulin is regulated within cells and is important for the stimulated secretion of EP24.15 from HEK293 cells. (PMID:19614740)
• mediates antigen processing that generates cytotoxic T cell epitopes (PMID:21151101)
• The semi-quantitative intracellular peptidome analyses of siRNA-transfected HEK293 cells shows that the levels of specific intracellular peptides are either increased or decreased upon EP24.15 inhibition. (PMID:22796113)
• shear-dependent TOP induction down-regulates MHC1 levels, pointing to a role for TOP in the flow-mediated regulation of endothelial immunogenicity (PMID:23708739)
• TCEP. Data indicate that THIMET-oligopeptidase (TOP) oxidation by H2O2 and high valence states of hemeproteins does not lead to enzyme oligomerization. (PMID:24223886)
• Low THOP1 expression levels are associated with recurrence of hepatocellular carcinoma. (PMID:24604581)
• THOP1 may have clinical potentials to be employed as a promising biomarker to identify individuals with better prognosis and a novel antitumor agent for therapy of patients with NSCLC (PMID:25180910)
• Data suggest that three new candidate genes involved in the development of rheumatoid arthritis (RA): ERBB2, TP53 and THOP1. (PMID:28148290)
• Expression of thimet oligopeptidase (THOP) modulated by oxidative stress in human multidrug resistant (MDR) leukemia cells. (PMID:36997147)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	thop1	ENSDARG00000013776
mus_musculus	Thop1	ENSMUSG00000004929
rattus_norvegicus	Thop1	ENSRNOG00000019924
drosophila_melanogaster	CG11771	FBGN0039252
caenorhabditis_elegans		WBGENE00013997

Paralogs (2): MIPEP (ENSG00000027001), NLN (ENSG00000123213)

Protein

Protein identifiers

Thimet oligopeptidase — P52888 (reviewed: P52888)

Alternative names: Endopeptidase 24.15, MP78

All UniProt accessions (5): P52888, K7EKB6, K7EL02, K7EL32, K7EMU4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation. Able to degrade the amyloid-beta precursor protein and generate amyloidogenic fragments. Also acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P52888-1	1	yes
P52888-2	2

RefSeq proteins (1): NP_003240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001567	Pept_M3A_M3B_dom	Domain
IPR024077	Neurolysin/TOP_dom2	Homologous_superfamily
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR024080	Neurolysin/TOP_N	Homologous_superfamily
IPR045090	Pept_M3A_M3B	Family

Pfam: PF01432

Enzyme classification (BRENDA):

• EC 3.4.24.15 — thimet oligopeptidase (BRENDA: 15 organisms, 317 substrates, 132 inhibitors, 249 Km, 258 kcat entries)

Substrate kinetics (BRENDA)

172 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(7-METHOXYCOUMARIN-4-YL)ACETYL-LEU-GLU-ASN-LYS-P	0.0012–0.0057	10
7-METHOXYCOUMARIN-4-ACETYL-PRO-LEU-GLY-PRO-LYS-D	0.004–0.009	10
7-METHOXYCOUMARIN-4-ACETYL-[ALA7, LYS(DINITROPHE	—	10
(7-METHOXYCOUMARIN-4-YL)-ACETYL-PRO-LEU-GLY-PRO-	0.0038–0.01	7
(7-METHOXYCOUMARIN-4-YL)ACETYL-GLU-HIS-TRP-SER-T	0.014–0.037	4
7-METHOXYCOUMARIN-4-ACETYL-(L-ALA-L-LYS(2,4-DINI	0.0001–0.0013	4
7-METHOXYCOUMARIN-4-ACETYL-PRO-LEU-GLY-PRO-LYS-(	0.004–0.01	4
2-AMINOBENZOYL-GFSPFRQ-(N-2,4-DINITROPHENYL)ETHY	0.0015–0.0043	3
7-METHOXYCOUMARIN-3-CARBOXYLYL-PRO-LEU-GLY-PRO-D	0.009–0.0343	3
ABZ-GFSAFRQEDDNP	0.0012–0.0098	3
ABZ-GFSEFRQEDDNP	0.0021–0.0075	3
ABZ-GFSFFRQEDDNP	0.0007–0.016	3
ABZ-GFSHFRQEDDNP	0.0076–0.0096	3
ABZ-GFSIFRQEDDNP	0.0004–0.005	3
ABZ-GFSLFRQEDDNP	0.0016–0.0102	3

UniProt features (64 total): helix 34, turn 10, strand 8, modified residue 5, binding site 3, splice variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2O36	X-RAY DIFFRACTION	1.95
1S4B	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52888-F1	94.11	0.91

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 (1): 474

Ligand- & substrate-binding residues (3): 473; 477; 480

Post-translational modifications (5): 16, 172, 257, 278, 538

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 150 (showing top): SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, RICKMAN_METASTASIS_DN, MODULE_195, MORF_BUB3, MORF_PRKDC

GO Biological Process (3): protein polyubiquitination (GO:0000209), proteolysis (GO:0006508), peptide metabolic process (GO:0006518)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (3): mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein ubiquitination	1
protein metabolic process	1
metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
mitochondrial envelope	1
organelle envelope lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THOP1	KNG1	P01042	890
THOP1	PREP	P48147	812
THOP1	CALM1	P02593	804
THOP1	STX6	O43752	710
THOP1	MMEL1	Q495T6	686
THOP1	NRDC	O43847	680
THOP1	CALML3	P27482	656
THOP1	CALML6	Q8TD86	656
THOP1	CALML4	Q96GE6	656
THOP1	CALML5	Q9NZT1	656
THOP1	MME	P08473	649
THOP1	TPP2	P29144	632
THOP1	ACE	P12821	612
THOP1	DPP3	Q9NY33	603
THOP1	NTS	P30990	597

IntAct

32 interactions, top by confidence:

A	B	Type	Score
NUAK2	PPP1R12A	psi-mi:“MI:0914”(association)	0.640
EPN2	THOP1	psi-mi:“MI:0915”(physical association)	0.560
THOP1	OPTN	psi-mi:“MI:0915”(physical association)	0.560
THOP1	Calm1	psi-mi:“MI:0407”(direct interaction)	0.560
XAGE2	WIZ	psi-mi:“MI:0914”(association)	0.530
THOP1	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
STK11	THOP1	psi-mi:“MI:0915”(physical association)	0.370
LRRK2		psi-mi:“MI:0914”(association)	0.350
PAPLN	PKM	psi-mi:“MI:0914”(association)	0.350
EXOSC3	EIF4E2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DEFB118	IFI30	psi-mi:“MI:0914”(association)	0.350
PAPLN	SDHB	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
PIDD1	IPO5	psi-mi:“MI:0914”(association)	0.350
CREB1	ACOT7	psi-mi:“MI:0914”(association)	0.350
CALM1	THOP1	psi-mi:“MI:0403”(colocalization)	0.270
IKBKE	THOP1	psi-mi:“MI:0915”(physical association)	0.000
THOP1	EPN2	psi-mi:“MI:0915”(physical association)	0.000
TTC3	THOP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (124): TRAF2 (Two-hybrid), THOP1 (Affinity Capture-MS), SYNE2 (Co-fractionation), THOP1 (Co-fractionation), TXNRD1 (Co-fractionation), THOP1 (Affinity Capture-MS), THOP1 (Two-hybrid), THOP1 (Two-hybrid), THOP1 (Affinity Capture-MS), THOP1 (Affinity Capture-RNA), THOP1 (Affinity Capture-MS), THOP1 (Affinity Capture-MS), THOP1 (Proximity Label-MS), THOP1 (Affinity Capture-MS), THOP1 (Two-hybrid)

ESM2 similar proteins: A2VDQ5, A4IG42, A6H611, A8E657, A8WFT6, A9RBS1, F4HTQ1, F4KDA5, O22190, P24155, P24527, P30349, P42675, P42676, P47788, P52888, P55786, Q01992, Q02038, Q09152, Q0VCA5, Q11011, Q1JPJ8, Q1MTD3, Q28FT4, Q32PX9, Q3T0H0, Q3V384, Q502K2, Q54DD2, Q56H28, Q5R9V6, Q5U5V2, Q6INN8, Q6P4Z6, Q6PB06, Q6S9C8, Q8BH66, Q8C1A5, Q8GWT4

Diamond homologs: A2VDQ5, F4HTQ1, P24155, P25375, P27237, P27298, P42675, P42676, P44573, P47788, P52888, Q02038, Q1JPJ8, Q54DD2, Q5R9V6, Q8C1A5, Q91YP2, Q9BYT8, P24171, P27236, Q949P2, Q94AM1, Q5RF14, Q99797

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	THOP1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	122
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3076 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2794762:A:AG	acceptor_gain	1.0000
19:2794763:G:GG	acceptor_gain	1.0000
19:2794763:GTTCA:G	acceptor_gain	1.0000
19:2794910:CAGG:C	donor_loss	1.0000
19:2794913:G:GC	donor_loss	1.0000
19:2794914:T:G	donor_loss	1.0000
19:2796184:AGGAA:A	donor_gain	1.0000
19:2796185:GGAA:G	donor_gain	1.0000
19:2796185:GGAAG:G	donor_gain	1.0000
19:2796186:G:GT	donor_gain	1.0000
19:2796186:G:T	donor_gain	1.0000
19:2796186:GAA:G	donor_gain	1.0000
19:2796186:GAAGT:G	donor_loss	1.0000
19:2796187:AA:A	donor_gain	1.0000
19:2796189:G:GG	donor_gain	1.0000
19:2796189:G:T	donor_loss	1.0000
19:2799683:CTCCA:C	acceptor_loss	1.0000
19:2799684:TCCA:T	acceptor_loss	1.0000
19:2799685:CCA:C	acceptor_loss	1.0000
19:2799686:CAGA:C	acceptor_loss	1.0000
19:2799687:A:AG	acceptor_gain	1.0000
19:2799687:AGA:A	acceptor_loss	1.0000
19:2799688:G:GA	acceptor_gain	1.0000
19:2799688:GA:G	acceptor_gain	1.0000
19:2799688:GAAC:G	acceptor_gain	1.0000
19:2799785:GAGC:G	donor_gain	1.0000
19:2799787:GCTAG:G	donor_gain	1.0000
19:2799788:C:G	donor_gain	1.0000
19:2805011:CATA:C	acceptor_loss	1.0000
19:2805013:TA:T	acceptor_loss	1.0000

AlphaMissense

4534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2808271:T:C	F428L	1.000
19:2808273:T:A	F428L	1.000
19:2808273:T:G	F428L	1.000
19:2808342:C:A	N451K	1.000
19:2808342:C:G	N451K	1.000
19:2808406:C:A	H473N	1.000
19:2808406:C:G	H473D	1.000
19:2808410:A:T	E474V	1.000
19:2808411:G:C	E474D	1.000
19:2808411:G:T	E474D	1.000
19:2808420:C:A	H477Q	1.000
19:2808420:C:G	H477Q	1.000
19:2810354:G:C	E502D	1.000
19:2810354:G:T	E502D	1.000
19:2794826:A:C	S98R	0.999
19:2794828:C:A	S98R	0.999
19:2794828:C:G	S98R	0.999
19:2807723:T:A	W390R	0.999
19:2807723:T:C	W390R	0.999
19:2808250:A:G	K421E	0.999
19:2808252:G:C	K421N	0.999
19:2808252:G:T	K421N	0.999
19:2808329:C:A	A447D	0.999
19:2808406:C:T	H473Y	0.999
19:2808408:T:A	H473Q	0.999
19:2808408:T:G	H473Q	0.999
19:2808416:G:A	G476D	0.999
19:2808418:C:A	H477N	0.999
19:2808418:C:G	H477D	0.999
19:2808418:C:T	H477Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000015330 (19:2812018 G>A), RS1000040403 (19:2785824 C>G), RS1000067817 (19:2811848 C>A,T), RS1000111577 (19:2796027 T>C), RS1000294017 (19:2815879 C>T), RS1000340729 (19:2785772 C>A,T), RS1000478121 (19:2785543 C>G,T), RS1000516034 (19:2804523 C>G,T), RS1000568368 (19:2804691 G>A), RS1000629805 (19:2808778 G>A,T), RS1000667390 (19:2791049 G>A,C,T), RS1000748294 (19:2815047 C>G), RS1000903126 (19:2790563 C>G,T), RS1001019602 (19:2812824 G>A), RS1001095312 (19:2787252 G>C,T)

Disease associations

OMIM: gene MIM:601117 | 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
GCST004235_7	Total cholesterol levels	8.000000e-08
GCST010204_52	Low density lipoprotein cholesterol levels	3.000000e-09
GCST90002400_259	Plateletcrit	2.000000e-14
GCST90002402_609	Platelet count	4.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291559 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	Kd	1993	nM	CHEMBL5653589
5.70	ED50	1993	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 7 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149583: Binding affinity to human THOP1 incubated for 45 mins by Kinobead based pull down assay	kd	1.9932	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	decreases expression, increases expression, affects cotreatment	2
sodium arsenite	increases expression	2
perfluorooctanoic acid	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
NSC 689534	affects binding, decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Ethanol	increases expression, affects cotreatment, increases abundance	1
Azathioprine	increases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5237351	Binding	Inhibition of recombinant human THOP catalytic activity using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)-OH as substrate	Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability. — 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_D1QY	Abcam K-562 THOP1 KO	Cancer cell line	Female
CVCL_D2MJ	Abcam Raji THOP1 KO	Cancer cell line	Male
CVCL_WQ67	Abcam Jurkat THOP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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