PRSS12

Summary

PRSS12 (serine protease 12, HGNC:9477) is a protein-coding gene on chromosome 4q26, encoding Neurotrypsin (P56730). Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations.

This gene encodes a member of the trypsin family of serine proteases and contains a signal peptide, a proline-rich region, a Kringle domain, four scavenger receptor cysteine-rich domains, and a trypsin-like serine protease domain. The protein, sometimes referred to as neurotrypsin or motopsin, is secreted from neuronal cells and localizes to the synaptic cleft. Studies in mice show that this protein cleaves a protein, agrin, that is important for the formation and maintenance of exitatory synapses. Defects in this gene cause a form of autosomal recessive cognitive impairment (MRT1).

Source: NCBI Gene 8492 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 1 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 318 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• MANE Select transcript: NM_003619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9477
Approved symbol	PRSS12
Name	serine protease 12
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	BSSP-3, MRT1
Ensembl gene	ENSG00000164099
Ensembl biotype	protein_coding
OMIM	606709
Entrez	8492

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000296498, ENST00000503043, ENST00000510903, ENST00000515089, ENST00000864359

RefSeq mRNA: 1 — MANE Select: NM_003619 NM_003619

CCDS: CCDS3709

Canonical transcript exons

ENST00000296498 — 13 exons

Exon	Start	End
ENSE00001081404	118331716	118331866
ENSE00001081406	118313201	118313397
ENSE00001081408	118338176	118338314
ENSE00001081409	118294939	118295061
ENSE00001081411	118280038	118282243
ENSE00001081412	118335473	118335651
ENSE00001081413	118282831	118283111
ENSE00001081414	118352219	118353003
ENSE00001081416	118298733	118298938
ENSE00001206430	118318378	118318556
ENSE00003535068	118316182	118316323
ENSE00003638074	118308436	118308577
ENSE00003681089	118295778	118295856

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 95.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1847 / max 548.3009, expressed in 1060 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53730	5.3240	969
53726	3.1175	568
53727	1.5374	508
53729	0.8893	445
53728	0.2291	136
53725	0.0874	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	95.29	gold quality
stromal cell of endometrium	CL:0002255	94.84	gold quality
epithelium of bronchus	UBERON:0002031	93.76	gold quality
bronchus	UBERON:0002185	92.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.89	gold quality
right uterine tube	UBERON:0001302	88.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.29	gold quality
nasal cavity mucosa	UBERON:0001826	86.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.27	gold quality
gall bladder	UBERON:0002110	85.60	gold quality
epithelium of nasopharynx	UBERON:0001951	84.39	gold quality
mammalian vulva	UBERON:0000997	83.97	gold quality
nasal cavity epithelium	UBERON:0005384	83.47	gold quality
mucosa of transverse colon	UBERON:0004991	83.31	gold quality
colonic epithelium	UBERON:0000397	82.68	gold quality
body of pancreas	UBERON:0001150	81.58	gold quality
right testis	UBERON:0004534	81.38	gold quality
rectum	UBERON:0001052	81.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.94	gold quality
left testis	UBERON:0004533	80.82	gold quality
vagina	UBERON:0000996	80.05	gold quality
ganglionic eminence	UBERON:0004023	79.88	gold quality
hair follicle	UBERON:0002073	79.64	silver quality
testis	UBERON:0000473	79.48	gold quality
pancreas	UBERON:0001264	77.16	gold quality
cortical plate	UBERON:0005343	77.16	gold quality
ectocervix	UBERON:0012249	77.00	gold quality
gingiva	UBERON:0001828	76.86	gold quality
endometrium	UBERON:0001295	76.66	gold quality
gingival epithelium	UBERON:0001949	76.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	209.70
E-ANND-3	yes	6.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

106 targeting PRSS12, 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-3924	100.00	72.09	2394
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-8063	99.91	69.76	3146

Literature-anchored findings (GeneRIF, showing 2)

• 4-base pair deletion in the neurotrypsin gene was associated with autosomal recessive nonsyndromic mental retardation; findings suggest that neurotrypsin-mediated proteolysis is required for normal synaptic function (PMID:12459588)
• Genes encoding agrin (AGRN) and neurotrypsin (PRSS12) are associated with muscle mass, strength and plasma C-terminal agrin fragment concentration. (PMID:36609795)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prss12	ENSDARG00000061830
mus_musculus	Prss12	ENSMUSG00000027978
rattus_norvegicus	Prss12	ENSRNOG00000015353

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), CD5 (ENSG00000110448), LOX (ENSG00000113083), LOXL3 (ENSG00000115318), LOXL1 (ENSG00000129038), LOXL2 (ENSG00000134013), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), CD163 (ENSG00000177575), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), DMBT1 (ENSG00000187908), SCART1 (ENSG00000214279)

Protein

Protein identifiers

Neurotrypsin — P56730 (reviewed: P56730)

Alternative names: Leydin, Motopsin, Serine protease 12

All UniProt accessions (1): P56730

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations.

Subcellular location. Secreted.

Tissue specificity. Brain and Leydig cells of the testis.

Disease relevance. Intellectual developmental disorder, autosomal recessive 1 (MRT1) [MIM:249500] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_003610* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR001190	SRCR	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504

Pfam: PF00051, PF00089, PF00530

UniProt features (43 total): disulfide bond 20, domain 6, sequence conflict 4, active site 3, glycosylation site 2, sequence variant 2, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56730-F1	77.42	0.35

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 (4): 676 (charge relay system); 726 (charge relay system); 825 (charge relay system); 630–631 (reactive bond homolog)

Disulfide bonds (20): 93–165, 109–149, 138–163, 195–259, 208–269, 239–249, 305–369, 318–379, 349–359, 412–475, 425–485, 455–465, 525–589, 538–599, 569–579, 619–750, 661–677, 765–831, 794–808, 821–850

Glycosylation sites (2): 26, 683

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOLDRATH_IMMUNE_MEMORY, MODULE_64, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_PROTEIN_MATURATION, MARTINEZ_RB1_TARGETS_DN, MODULE_109, BROWNE_HCMV_INFECTION_14HR_DN, MODULE_99, GOBP_SECRETION, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, AACTTT_UNKNOWN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, GOCC_NEURON_PROJECTION

GO Biological Process (3): exocytosis (GO:0006887), zymogen activation (GO:0031638), proteolysis (GO:0006508)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (12): plasma membrane (GO:0005886), axon (GO:0030424), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), synaptic cleft (GO:0043083), terminal bouton (GO:0043195), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), extracellular region (GO:0005576), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	3
neuron projection	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
protein processing	1
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
membrane	1
cell periphery	1
dendritic tree	1
cytoplasm	1
intracellular vesicle	1
extracellular region	1
axon terminus	1
presynapse	1
cell junction	1

Protein interactions and networks

STRING

890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS12	CC2D1A	Q6P1N0	909
PRSS12	CRBN	Q96SW2	846
PRSS12	AGRN	O00468	742
PRSS12	CA4	P22748	713
PRSS12	MUSK	O15146	609
PRSS12	SCN4B	Q8IWT1	474
PRSS12	DOK7	Q18PE1	464
PRSS12	SYT2	Q8N9I0	460
PRSS12	RAPSN	Q13702	453
PRSS12	DPP3	Q9NY33	449
PRSS12	MMP9	P14780	443
PRSS12	L1CAM	P32004	424
PRSS12	ADAM10	O14672	410
PRSS12	CNTNAP4	Q9C0A0	406
PRSS12	MYO9A	B2RTY4	403

IntAct

14 interactions, top by confidence:

A	B	Type	Score
PRSS12	PRPF40A	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
MFAP5	MANBA	psi-mi:“MI:0914”(association)	0.350
LY86	PLXNB2	psi-mi:“MI:0914”(association)	0.350
INS	LAMA5	psi-mi:“MI:0914”(association)	0.350
MSMB	ADAM11	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
EPDR1	DUSP14	psi-mi:“MI:0914”(association)	0.350
	NFIB	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): SH3PXD2A (Affinity Capture-MS), PPIL3 (Affinity Capture-MS), CNTLN (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS), PRSS12 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, D3ZTE0, G3V801, O08762, O43866, O75636, O95428, O97507, P00748, P22457, P56730, P58215, P69525, P69526, P85521, P98140, Q02853, Q04756, Q04962, Q24K22, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q499S5, Q4G0T1, Q5G265, Q5G268, Q5G269, Q5G270, Q5G271, Q5IJ48, Q6QNF4, Q70UZ7, Q769J6, Q76LX8, Q7Z410, Q80YA8, Q80YC5

Diamond homologs: A0A182C2Z2, B8V7S0, O08762, O60235, P00747, P00760, P00762, P00765, P00766, P00767, P00774, P03951, P03952, P04070, P04813, P05981, P06867, P06871, P06872, P07146, P07338, P07477, P08217, P08426, P08519, P12545, P14272, P15944, P17538, P19799, P20231, P20918, P26262, P27435, P29786, P35033, P40313, P47796, P50342, P56677

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	246
Likely benign	31
Benign	9

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
443483	GRCh37/hg19 4q22.1-35.2(chr4:93071152-190957473)x3	Pathogenic
1676513	NM_003619.4(PRSS12):c.441_442del (p.Trp148fs)	Likely pathogenic
3780493	NM_003619.4(PRSS12):c.1586G>A (p.Trp529Ter)	Likely pathogenic
4849491	NM_003619.4(PRSS12):c.1022del (p.Pro341fs)	Likely pathogenic

SpliceAI

2323 predictions. Top by Δscore:

Variant	Effect	Δscore
4:118298730:TAC:T	donor_loss	1.0000
4:118298731:A:AC	donor_gain	1.0000
4:118298732:C:CC	donor_gain	1.0000
4:118298732:C:CG	donor_loss	1.0000
4:118298732:CCTTT:C	donor_gain	1.0000
4:118298936:CCC:C	acceptor_gain	1.0000
4:118298937:CC:C	acceptor_gain	1.0000
4:118298937:CCC:C	acceptor_gain	1.0000
4:118298937:CCCT:C	acceptor_loss	1.0000
4:118298938:CC:C	acceptor_gain	1.0000
4:118298939:C:CC	acceptor_gain	1.0000
4:118298939:C:T	acceptor_gain	1.0000
4:118308430:CCTTA:C	donor_loss	1.0000
4:118308431:CTT:C	donor_loss	1.0000
4:118308432:TTAC:T	donor_loss	1.0000
4:118308433:T:TG	donor_loss	1.0000
4:118308434:A:AC	donor_gain	1.0000
4:118308434:A:AT	donor_loss	1.0000
4:118308435:C:CT	donor_gain	1.0000
4:118316180:A:AC	donor_gain	1.0000
4:118316181:C:CC	donor_gain	1.0000
4:118316184:AAAT:A	donor_gain	1.0000
4:118316184:AAATC:A	donor_gain	1.0000
4:118318552:TGCCA:T	acceptor_gain	1.0000
4:118318554:CCA:C	acceptor_gain	1.0000
4:118318555:CAC:C	acceptor_gain	1.0000
4:118318557:C:CC	acceptor_gain	1.0000
4:118331711:CAAA:C	donor_loss	1.0000
4:118331712:AAAC:A	donor_loss	1.0000
4:118331713:AAC:A	donor_loss	1.0000

AlphaMissense

5689 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:118298864:C:G	C569S	0.999
4:118298865:A:T	C569S	0.999
4:118308480:C:A	W529C	0.999
4:118308480:C:G	W529C	0.999
4:118308482:A:G	W529R	0.999
4:118308482:A:T	W529R	0.999
4:118308493:C:G	C525S	0.999
4:118308493:C:T	C525Y	0.999
4:118308494:A:T	C525S	0.999
4:118331760:C:A	W309C	0.999
4:118331760:C:G	W309C	0.999
4:118282841:C:A	W770C	0.998
4:118282841:C:G	W770C	0.998
4:118294947:A:C	C677W	0.998
4:118298865:A:G	C569R	0.998
4:118308492:A:C	C525W	0.998
4:118308493:C:A	C525F	0.998
4:118308494:A:G	C525R	0.998
4:118318482:C:G	C349S	0.998
4:118318483:A:T	C349S	0.998
4:118295046:C:A	W644C	0.997
4:118295046:C:G	W644C	0.997
4:118298774:C:G	C599S	0.997
4:118298775:A:T	C599S	0.997
4:118298804:C:G	C589S	0.997
4:118298805:A:T	C589S	0.997
4:118298833:A:C	C579W	0.997
4:118298834:C:G	C579S	0.997
4:118298835:A:T	C579S	0.997
4:118308453:A:C	C538W	0.997

dbSNP variants (sampled 300 via entrez): RS1000001334 (4:118354549 T>C), RS1000020477 (4:118327769 T>C), RS1000057311 (4:118337615 A>C), RS1000074015 (4:118345020 G>T), RS10000812 (4:118349639 T>C), RS1000188574 (4:118344665 A>G), RS10002349 (4:118311237 A>T), RS10002475 (4:118304090 C>G,T), RS1000279361 (4:118285836 G>T), RS1000339100 (4:118306080 G>A), RS10003730 (4:118290218 T>C), RS1000487010 (4:118312898 G>C,T), RS1000539475 (4:118300079 C>A,T), RS1000593669 (4:118321632 C>T), RS1000625526 (4:118329832 A>G)

Disease associations

OMIM: gene MIM:606709 | disease phenotypes: MIM:249500

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 1	Definitive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
non-syndromic intellectual disability	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
non-syndromic intellectual disability	Limited	AR

Mondo (4): intellectual disability, autosomal recessive 1 (MONDO:0009580), long QT syndrome (MONDO:0002442), non-syndromic intellectual disability (MONDO:0000509), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (1): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0002151	Increased circulating lactate concentration
HP:0003487	Babinski sign
HP:0006801	Hyperactive deep tendon reflexes
HP:0010864	Severe intellectual disability
HP:0011463	Childhood onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004721_19	Congenital heart disease (maternal effect)	8.000000e-06
GCST009391_1901	Metabolite levels	4.000000e-06
GCST010397_82	Gut microbiota (bacterial taxa, rank normal transformation method)	8.000000e-06
GCST011617_11	Cortical surface area	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010462	aspartate measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C565406	Mental Retardation, Autosomal Recessive 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523246 (SINGLE PROTEIN)

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

ChEMBL bioactivities

117 potent at pChembl≥5 of 139 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.40	IC50	400	nM	CHEMBL4592545
6.30	IC50	500	nM	CHEMBL4535612
6.30	IC50	500	nM	CHEMBL4540922
6.30	IC50	500	nM	CHEMBL4513696
6.30	IC50	500	nM	CHEMBL4518469
6.29	IC50	510	nM	CHEMBL4574612
6.16	IC50	700	nM	CHEMBL4539049
6.10	IC50	800	nM	CHEMBL4514750
6.05	IC50	900	nM	CHEMBL4577465
6.05	IC50	900	nM	CHEMBL4591214
6.00	IC50	1000	nM	CHEMBL4518199
5.92	IC50	1200	nM	CHEMBL4562490
5.92	IC50	1200	nM	CHEMBL4524777
5.82	IC50	1500	nM	CHEMBL4563075
5.80	IC50	1600	nM	CHEMBL4586467
5.80	IC50	1600	nM	CHEMBL4587461
5.72	IC50	1900	nM	CHEMBL4592966
5.72	IC50	1900	nM	CHEMBL4515111
5.72	IC50	1900	nM	CHEMBL4582617
5.72	IC50	1900	nM	CHEMBL4545329
5.66	IC50	2200	nM	CHEMBL4568868
5.66	IC50	2200	nM	CHEMBL4578461
5.64	IC50	2300	nM	CHEMBL4518659
5.62	IC50	2400	nM	CHEMBL4538329
5.62	IC50	2400	nM	CHEMBL4540979
5.62	IC50	2400	nM	CHEMBL4592742
5.60	IC50	2500	nM	CHEMBL4563644
5.58	IC50	2600	nM	CHEMBL4589797
5.58	IC50	2600	nM	CHEMBL4546402
5.57	IC50	2700	nM	CHEMBL4565029
5.57	IC50	2700	nM	CHEMBL4537572
5.55	IC50	2800	nM	CHEMBL4570742
5.54	IC50	2900	nM	CHEMBL4527216
5.52	IC50	3000	nM	CHEMBL4522158
5.52	IC50	3000	nM	CHEMBL4544161
5.52	IC50	3000	nM	CHEMBL4543861
5.51	IC50	3100	nM	CHEMBL4540328
5.51	IC50	3100	nM	CHEMBL4560639
5.51	IC50	3100	nM	CHEMBL4580876
5.50	IC50	3200	nM	CHEMBL4563948
5.50	IC50	3200	nM	CHEMBL4555979
5.48	IC50	3300	nM	CHEMBL4526196
5.47	IC50	3400	nM	CHEMBL4575400
5.47	IC50	3400	nM	CHEMBL4590547
5.47	IC50	3400	nM	CHEMBL4575707
5.47	IC50	3400	nM	CHEMBL4567910
5.46	IC50	3500	nM	CHEMBL4527733
5.46	IC50	3500	nM	CHEMBL4543302
5.46	IC50	3500	nM	CHEMBL4555092
5.46	IC50	3500	nM	CHEMBL4521886

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Temozolomide	increases expression, affects response to substance	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	increases methylation, affects cotreatment, decreases expression, increases abundance	2
Doxorubicin	increases expression, affects expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, decreases expression	1
methylparaben	decreases expression	1
ethylene dichloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dimethylarsinous acid	decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Azacitidine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4476902	Binding	Inhibition of human neurotrypsin	Neurotrypsin inhibitors

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea