TRHDE

Summary

TRHDE (thyrotropin releasing hormone degrading enzyme, HGNC:30748) is a protein-coding gene on chromosome 12q21.1, encoding Thyrotropin-releasing hormone-degrading ectoenzyme (Q9UKU6). Specific inactivation of TRH after its release.

This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.

Source: NCBI Gene 29953 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 129 total
• Druggable target: yes
• MANE Select transcript: NM_013381

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30748
Approved symbol	TRHDE
Name	thyrotropin releasing hormone degrading enzyme
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PGPEP2, TRH-DE, PAP-II
Ensembl gene	ENSG00000072657
Ensembl biotype	protein_coding
OMIM	606950
Entrez	29953

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding_CDS_not_defined, 2 protein_coding, 1 retained_intron

ENST00000261180, ENST00000547300, ENST00000548156, ENST00000549138, ENST00000549401, ENST00000549922, ENST00000552503

RefSeq mRNA: 1 — MANE Select: NM_013381 NM_013381

CCDS: CCDS9004

Canonical transcript exons

ENST00000261180 — 19 exons

Exon	Start	End
ENSE00000752414	72473067	72473180
ENSE00000911441	72499498	72499635
ENSE00000911442	72542291	72542356
ENSE00000937466	72272370	72273557
ENSE00000993940	72653016	72653156
ENSE00000993941	72621644	72621751
ENSE00000993942	72621108	72621205
ENSE00000993943	72656927	72657008
ENSE00000993944	72652322	72652489
ENSE00001236769	72663052	72670758
ENSE00003488526	72618891	72619038
ENSE00003510891	72469758	72469912
ENSE00003519354	72377995	72378121
ENSE00003521609	72562165	72562230
ENSE00003552303	72568568	72568656
ENSE00003593892	72562853	72563040
ENSE00003595483	72575255	72575388
ENSE00003667127	72575487	72575542
ENSE00003671122	72286681	72286954

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 91.41.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9726 / max 234.1410, expressed in 694 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126857	1.1253	460
126859	0.5911	229
126858	0.4923	213
126860	0.3129	137
126861	0.1849	83
126866	0.1369	63
126868	0.0755	29
126867	0.0410	13
126847	0.0106	3
126848	0.0021	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	91.41	gold quality
stromal cell of endometrium	CL:0002255	89.07	gold quality
endothelial cell	CL:0000115	87.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.13	gold quality
nephron tubule	UBERON:0001231	82.72	gold quality
orbitofrontal cortex	UBERON:0004167	82.58	gold quality
superior frontal gyrus	UBERON:0002661	81.64	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.54	gold quality
postcentral gyrus	UBERON:0002581	80.93	gold quality
middle temporal gyrus	UBERON:0002771	80.43	gold quality
body of pancreas	UBERON:0001150	80.37	gold quality
primary visual cortex	UBERON:0002436	79.76	gold quality
parietal lobe	UBERON:0001872	79.72	gold quality
duodenum	UBERON:0002114	78.97	gold quality
occipital lobe	UBERON:0002021	77.49	gold quality
prefrontal cortex	UBERON:0000451	76.85	gold quality
kidney epithelium	UBERON:0004819	76.20	gold quality
lower lobe of lung	UBERON:0008949	75.15	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.04	gold quality
frontal cortex	UBERON:0001870	74.69	gold quality
pancreas	UBERON:0001264	74.31	gold quality
entorhinal cortex	UBERON:0002728	74.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.81	gold quality
endocervix	UBERON:0000458	73.72	gold quality
ectocervix	UBERON:0012249	73.70	gold quality
cerebellum	UBERON:0002037	73.51	gold quality
epithelial cell of pancreas	CL:0000083	73.39	silver quality
metanephric glomerulus	UBERON:0004736	73.22	gold quality
neocortex	UBERON:0001950	73.15	gold quality
cerebellar cortex	UBERON:0002129	73.12	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	758.74
E-HCAD-35	yes	64.36
E-ANND-3	yes	14.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

215 targeting TRHDE, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
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-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8068	99.98	73.85	2376
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	trhde.1	ENSDARG00000109358
danio_rerio	trhde.2	ENSDARG00000111837
mus_musculus	Trhde	ENSMUSG00000050663
rattus_norvegicus	Trhde	ENSRNOG00000005278
drosophila_melanogaster	CG7653	FBGN0028935
drosophila_melanogaster	CG9806	FBGN0030222
drosophila_melanogaster	CG2111	FBGN0030223
drosophila_melanogaster	CG6071	FBGN0036186
drosophila_melanogaster	CG5849	FBGN0038897
drosophila_melanogaster	CG3502	FBGN0046253
drosophila_melanogaster	CG31233	FBGN0051233
drosophila_melanogaster	CG31343	FBGN0051343
drosophila_melanogaster	CG31445	FBGN0051445
drosophila_melanogaster	SP1029	FBGN0263236
drosophila_melanogaster	CG46339	FBGN0285963
caenorhabditis_elegans	F49B2.6	WBGENE00009865
caenorhabditis_elegans		WBGENE00011587
caenorhabditis_elegans		WBGENE00012776

Paralogs (11): LTA4H (ENSG00000111144), LNPEP (ENSG00000113441), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), AOPEP (ENSG00000148120), ERAP1 (ENSG00000164307), ERAP2 (ENSG00000164308), ANPEP (ENSG00000166825), LVRN (ENSG00000172901), RNPEP (ENSG00000176393)

Protein

Protein identifiers

Thyrotropin-releasing hormone-degrading ectoenzyme — Q9UKU6 (reviewed: Q9UKU6)

Alternative names: Pyroglutamyl-peptidase II, TRH-specific aminopeptidase, Thyroliberinase

All UniProt accessions (2): Q9UKU6, A0AA75K8V0

UniProt curated annotations — full annotation on UniProt →

Function. Specific inactivation of TRH after its release.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Membrane.

Tissue specificity. Predominantly expressed in brain.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M1 family.

RefSeq proteins (1): NP_037513* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001930	Peptidase_M1	Family
IPR014782	Peptidase_M1_dom	Domain
IPR024571	ERAP1-like_C_dom	Domain
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR034016	M1_APN-typ	Family
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR045357	Aminopeptidase_N-like_N	Domain
IPR050344	Peptidase_M1_aminopeptidases	Family

Pfam: PF01433, PF11838, PF17900

UniProt features (29 total): glycosylation site 12, binding site 4, compositionally biased region 3, topological domain 2, region of interest 2, chain 1, site 1, transmembrane region 1, disulfide bond 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKU6-F1	85.49	0.67

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): 572 (transition state stabilizer); 486 (proton acceptor)

Ligand- & substrate-binding residues (4): 449–453; 485; 489; 508

Disulfide bonds (1): 113

Glycosylation sites (12): 134, 205, 220, 267, 383, 650, 679, 694, 708, 729, 845, 951

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, GOBP_PEPTIDE_METABOLIC_PROCESS, GGGCATT_MIR365, chr12q21, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOBP_PEPTIDE_CATABOLIC_PROCESS, NOUZOVA_METHYLATED_IN_APL, SCHLESINGER_H3K27ME3_IN_NORMAL_AND_METHYLATED_IN_CANCER, NUYTTEN_EZH2_TARGETS_DN, GOBP_PROTEOLYSIS, AAGCACA_MIR218, GOMF_METALLOEXOPEPTIDASE_ACTIVITY

GO Biological Process (4): proteolysis (GO:0006508), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), peptide catabolic process (GO:0043171)

GO Molecular Function (8): aminopeptidase activity (GO:0004177), zinc ion binding (GO:0008270), pyroglutamyl-peptidase activity (GO:0016920), metalloaminopeptidase activity (GO:0070006), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
protein metabolic process	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
peptide metabolic process	1
catabolic process	1
exopeptidase activity	1
transition metal ion binding	1
cysteine-type peptidase activity	1
omega peptidase activity	1
aminopeptidase activity	1
metalloexopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRHDE	TRH	P20396	933
TRHDE	PGPEP1	Q9NXJ5	687
TRHDE	PREP	P48147	421
TRHDE	CAMKMT	Q7Z624	396
TRHDE	PRLR	P16471	387
TRHDE	MEF2B	Q02080	374
TRHDE	COX5B	P10606	371
TRHDE	RFXANK	O14593	362
TRHDE	NR3C1	P04150	357
TRHDE	ALDH18A1	P54886	350
TRHDE	LRRC63	Q05C16	340
TRHDE	BMS1	Q14692	339
TRHDE	SLCO1C1	Q9NYB5	328
TRHDE	TBCB	Q99426	324
TRHDE	DIO2	Q92813	323

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
TRHDE	MAN1A2	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
TRHDE	CKAP4	psi-mi:“MI:0915”(physical association)	0.400
	HAX1	psi-mi:“MI:0914”(association)	0.350
AKT1	TPM2	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LCN6	POTEF	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
C1QB	MANBA	psi-mi:“MI:0914”(association)	0.350
FIBIN	MAN2B1	psi-mi:“MI:0914”(association)	0.350
TSPAN3	SCAMP3	psi-mi:“MI:0914”(association)	0.350
CLRN2	CA12	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	MGRN1	psi-mi:“MI:0914”(association)	0.350
ICOS	TNFSF9	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SCHIP1	TRHDE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): TRHDE (Affinity Capture-MS), MUL1 (Affinity Capture-MS), TSPAN3 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), EMILIN2 (Affinity Capture-MS), MANEA (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), KIRREL (Affinity Capture-MS), CANX (Affinity Capture-MS), TMTC3 (Affinity Capture-MS), MESDC2 (Affinity Capture-MS), MAN1A2 (Affinity Capture-MS), TRHDE (Proximity Label-MS), TRHDE (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A6NKP2, A6QLY2, O18735, O43488, O75382, O75648, O77485, O77486, O88676, P04626, P23764, P25325, P34059, P52848, Q02353, Q0VD18, Q10836, Q10981, Q10982, Q28113, Q32KH5, Q32KJ6, Q3U129, Q3UHN9, Q4R766, Q571E4, Q5I0D5, Q5RB73, Q5RJL2, Q6AYT7, Q6P988, Q7RTV5, Q7Z4H8, Q8CIW5, Q8K093, Q8N2K0, Q8WNQ7, Q96AZ1, Q96SL4

Diamond homologs: A0A6J2ATK2, A6NEC2, A6QPT7, M3XFH7, O57579, P15144, P15145, P15541, P15684, P46557, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10736, Q10836, Q2KHK3, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q8C129, Q8K093, Q95334, Q9EQH2, Q9JJ22, Q9UIQ6, Q9UKU6, A5HUI5, D3UW23, O93654, O93655, P0DQU2, P16406, P32454, P37893

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4508 predictions. Top by Δscore:

Variant	Effect	Δscore
12:72286395:G:GG	donor_gain	1.0000
12:72286838:G:GT	donor_gain	1.0000
12:72309780:A:T	donor_gain	1.0000
12:72309797:G:GT	donor_gain	1.0000
12:72377991:TTAGG:T	acceptor_loss	1.0000
12:72377992:TA:T	acceptor_loss	1.0000
12:72377993:A:T	acceptor_loss	1.0000
12:72377994:G:GA	acceptor_loss	1.0000
12:72378118:CTAGG:C	donor_loss	1.0000
12:72378120:AGGTA:A	donor_loss	1.0000
12:72378121:GGT:G	donor_loss	1.0000
12:72378123:T:A	donor_loss	1.0000
12:72473061:CTGCA:C	acceptor_loss	1.0000
12:72473062:TGCAG:T	acceptor_loss	1.0000
12:72473063:GCAGT:G	acceptor_loss	1.0000
12:72473064:CAGTG:C	acceptor_loss	1.0000
12:72473065:A:AG	acceptor_gain	1.0000
12:72473065:A:G	acceptor_loss	1.0000
12:72473065:AGT:A	acceptor_gain	1.0000
12:72473065:AGTG:A	acceptor_gain	1.0000
12:72473066:G:A	acceptor_loss	1.0000
12:72473066:G:GA	acceptor_gain	1.0000
12:72473066:GT:G	acceptor_gain	1.0000
12:72473066:GTG:G	acceptor_gain	1.0000
12:72473066:GTGG:G	acceptor_gain	1.0000
12:72473066:GTGGT:G	acceptor_gain	1.0000
12:72473177:CATG:C	donor_gain	1.0000
12:72473179:TGGT:T	donor_loss	1.0000
12:72473180:GGT:G	donor_loss	1.0000
12:72473181:G:GA	donor_loss	1.0000

AlphaMissense

7024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:72473099:G:C	W456C	1.000
12:72473099:G:T	W456C	1.000
12:72621675:T:C	C822R	1.000
12:72621676:G:A	C822Y	1.000
12:72621677:C:G	C822W	1.000
12:72621696:T:C	C829R	1.000
12:72621697:G:A	C829Y	1.000
12:72621698:T:G	C829W	1.000
12:72621729:T:A	W840R	1.000
12:72621729:T:C	W840R	1.000
12:72652354:G:A	C858Y	1.000
12:72652355:T:G	C858W	1.000
12:72652386:T:A	W869R	1.000
12:72652386:T:C	W869R	1.000
12:72652388:G:C	W869C	1.000
12:72652388:G:T	W869C	1.000
12:72652452:G:C	A891P	1.000
12:72653018:T:C	L904P	1.000
12:72653021:T:C	L905P	1.000
12:72653102:G:A	G932D	1.000
12:72273517:G:C	G247R	0.999
12:72286716:C:A	A272D	0.999
12:72286719:G:C	R273T	0.999
12:72286719:G:T	R273I	0.999
12:72286734:G:A	C278Y	0.999
12:72286735:T:G	C278W	0.999
12:72286739:G:C	D280H	0.999
12:72286740:A:T	D280V	0.999
12:72286756:G:C	K285N	0.999
12:72286756:G:T	K285N	0.999

dbSNP variants (sampled 300 via entrez): RS1000008738 (12:72529703 A>T), RS1000016248 (12:72196892 A>G,T), RS1000020537 (12:72569614 A>G), RS1000032129 (12:72166571 A>G), RS1000034002 (12:72109657 G>C), RS1000035854 (12:72634881 T>A,G), RS1000048270 (12:72614976 C>G), RS1000058099 (12:72514078 A>G), RS1000059040 (12:72175956 C>T), RS1000059351 (12:72424873 G>T), RS1000062514 (12:72529933 C>T), RS1000063499 (12:72210374 G>A), RS1000079098 (12:72114212 C>T), RS1000079816 (12:72471168 G>A), RS1000084215 (12:72523235 G>A,T)

Disease associations

OMIM: gene MIM:606950 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000628_5	Chemerin levels	9.000000e-06
GCST001022_4	Rheumatoid arthritis	6.000000e-06
GCST002120_3	Metabolite levels (Dihydroxy docosatrienoic acid)	9.000000e-06
GCST002892_12	Perioperative myocardial infarction in coronary artery bypass surgery	9.000000e-06
GCST003671_9	Diastolic blood pressure	8.000000e-06
GCST007325_131	General risk tolerance (MTAG)	7.000000e-11
GCST008529_57	Tea consumption	1.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004573	chemerin measurement
EFO:0005275	dihydroxy docosatrienoic acid measurement
EFO:0006336	diastolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0010091	tea consumption measurement

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3886123 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M1: Aminopeptidase N

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.10	Ki	8000	nM	CHEMBL3897627

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	7
Benzo(a)pyrene	affects methylation, decreases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases methylation	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
terbufos	increases methylation	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
methylenediphenyl diisocyanate-glutathione adduct	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
incobotulinumtoxinA	increases expression	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression, decreases reaction	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Methapyrilene	decreases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Parathion	increases methylation	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
CHEMBL3880476	Binding	Competitive inhibition of TRH-DE (unknown origin)	TRH-like peptide derivatives as inhibitors of the TRH-degrading ectoenzyme

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