PEX5L

Summary

PEX5L (peroxisomal biogenesis factor 5 like, HGNC:30024) is a protein-coding gene on chromosome 3q26.33, encoding PEX5-related protein (Q8IYB4). Accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.

Enables peroxisome matrix targeting signal-1 binding activity and small GTPase binding activity. Predicted to be involved in protein import into peroxisome matrix, docking. Predicted to act upstream of or within maintenance of protein location and regulation of membrane potential. Located in cytosol. Part of receptor complex.

Source: NCBI Gene 51555 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_016559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30024
Approved symbol	PEX5L
Name	peroxisomal biogenesis factor 5 like
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Aliases	PEX5R, PXR2, TRIP8b
Ensembl gene	ENSG00000114757
Ensembl biotype	protein_coding
OMIM	611058
Entrez	51555

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000263962, ENST00000392649, ENST00000461537, ENST00000463761, ENST00000464614, ENST00000465751, ENST00000467440, ENST00000467460, ENST00000468741, ENST00000469198, ENST00000472994, ENST00000474909, ENST00000476138, ENST00000477829, ENST00000485199, ENST00000487198, ENST00000491640, ENST00000496721

RefSeq mRNA: 28 — MANE Select: NM_016559 NM_001256750, NM_001256751, NM_001256752, NM_001256753, NM_001256754, NM_001256755, NM_001256756, NM_001349386, NM_001349387, NM_001349388, NM_001349389, NM_001349390, NM_001349391, NM_001349392, NM_001349393, NM_001349394, NM_001349395, NM_001349396, NM_001349397, NM_001349398, NM_001349399, NM_001349401, NM_001349404, NM_001349406, NM_001349408, NM_001349409, NM_001349410, NM_016559

CCDS: CCDS3236, CCDS58861, CCDS58862, CCDS58863, CCDS58864, CCDS58865, CCDS58866, CCDS58867

Canonical transcript exons

ENST00000467460 — 15 exons

Exon	Start	End
ENSE00001922947	180036579	180036937
ENSE00001942214	179794958	179802032
ENSE00003483558	179815861	179816004
ENSE00003485158	179859062	179859157
ENSE00003489130	179898142	179898246
ENSE00003508211	179809471	179809668
ENSE00003512636	179874327	179874423
ENSE00003514791	179819860	179819976
ENSE00003514916	179971594	179971665
ENSE00003527673	179811801	179811871
ENSE00003530594	179808272	179808437
ENSE00003531609	179879929	179880123
ENSE00003565526	179887673	179887784
ENSE00003604061	179875354	179875477
ENSE00003612485	179807674	179807831

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 98.17.

FANTOM5 (CAGE): breadth broad, TPM avg 10.1292 / max 947.3385, expressed in 354 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45734	4.0697	174
45742	1.8951	208
45739	1.5472	172
45740	1.4038	163
45738	0.5346	130
45741	0.2183	87
45737	0.2088	96
45735	0.1584	51
45733	0.0652	22
45736	0.0280	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.11	gold quality
inferior vagus X ganglion	UBERON:0005363	96.09	gold quality
corpus callosum	UBERON:0002336	96.08	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.72	gold quality
middle temporal gyrus	UBERON:0002771	95.50	gold quality
subthalamic nucleus	UBERON:0001906	95.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.94	gold quality
substantia nigra pars compacta	UBERON:0001965	94.75	gold quality
primary visual cortex	UBERON:0002436	94.70	gold quality
sural nerve	UBERON:0015488	94.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.97	gold quality
occipital lobe	UBERON:0002021	93.39	gold quality
parietal lobe	UBERON:0001872	93.31	gold quality
postcentral gyrus	UBERON:0002581	93.20	gold quality
spinal cord	UBERON:0002240	93.17	gold quality
superior frontal gyrus	UBERON:0002661	93.04	gold quality
entorhinal cortex	UBERON:0002728	93.04	gold quality
prefrontal cortex	UBERON:0000451	92.86	gold quality
ventral tegmental area	UBERON:0002691	92.60	gold quality
medial globus pallidus	UBERON:0002477	92.31	gold quality
globus pallidus	UBERON:0001875	92.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.55	gold quality
superior vestibular nucleus	UBERON:0007227	90.95	gold quality
lateral globus pallidus	UBERON:0002476	90.11	gold quality
cortical plate	UBERON:0005343	90.05	gold quality
frontal cortex	UBERON:0001870	89.98	gold quality
pons	UBERON:0000988	89.90	gold quality
Ammon’s horn	UBERON:0001954	89.56	gold quality
trigeminal ganglion	UBERON:0001675	89.52	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2980.75
E-MTAB-11121	yes	887.61
E-HCAD-35	yes	94.94
E-HCAD-25	yes	49.23
E-MTAB-7316	yes	27.34
E-CURD-114	yes	11.56
E-ANND-3	yes	10.62
E-GEOD-137537	yes	4.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

263 targeting PEX5L, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
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-6867-5P	100.00	82.21	3464
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 9)

• increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. (PMID:21504900)
• TRIP8b interacts with the carboxyl-terminal region of HCN channels and regulates their cell-surface expression level and cyclic nucleotide dependence. (PMID:22550182)
• Seizure-dependent plasticity wound is not conditional upon TRIP8b in cerebral cortex. (PMID:23077068)
• Nedd4-2 plays an important role in the regulation of HCN1 trafficking and may compete with TRIP8b(1a-4) in this process (PMID:24451387)
• Data show that Rab8b-interacting protein TRIP8b does not compete with cyclic AMP for the same binding region of hyperpolarization activated cyclic nucleotide gated potassium channel 2 (HCN2). (PMID:25197093)
• the sequential formation of a highly stable trimeric complex involving cargo protein, PEX7 and PEX5L stabilizes cargo binding and is a prerequisite for PTS2-mediated peroxisomal import. (PMID:25538232)
• TRIP8b competes with a portion of the cAMP-binding site or distorts the binding site by making interactions with the binding pocket, thus acting predominantly as a competitive antagonist that inhibits the cyclic-nucleotide dependence of HCN channels. (PMID:28864772)
• allosteric coupling of the TRIP8b TPR domains both promotes binding to HCN channels and limits binding to type 1 peroxisomal targeting signal substrates. (PMID:28887304)
• Genetic variants in DDO and PEX5L in peroxisome-related pathways predict non-small cell lung cancer survival. (PMID:35502931)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex5la	ENSDARG00000022518
danio_rerio	pex5lb	ENSDARG00000074403
mus_musculus	Pex5l	ENSMUSG00000027674
rattus_norvegicus	Pex5l	ENSRNOG00000011211
drosophila_melanogaster	Pex5	FBGN0023516
caenorhabditis_elegans		WBGENE00004194

Paralogs (1): PEX5 (ENSG00000139197)

Protein

Protein identifiers

PEX5-related protein — Q8IYB4 (reviewed: Q8IYB4)

Alternative names: PEX2-related protein, PEX5-like protein, Peroxin-5-related protein, Peroxisome biogenesis factor 5-like, Tetratricopeptide repeat-containing Rab8b-interacting protein

All UniProt accessions (5): Q8IYB4, C9IZ09, C9JB85, C9JUZ5, C9JZE2

UniProt curated annotations — full annotation on UniProt →

Function. Accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.

Subunit / interactions. Interacts with RAB8B. Forms an obligate 4:4 complex with HCN2. May interact with the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type); the relevance of such interaction is however unclear. Interacts with HCN3. Interacts with HCN4 with a 4:4 HCN4:PEX5L stoichiometry; reduces the effects of cAMP on the voltage-dependence and rate of activation of HCN4.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Mainly expressed in brain. Also expressed in pancreas, testis and pituitary.

Similarity. Belongs to the peroxisomal targeting signal receptor family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q8IYB4-1	1, PXR2b	yes
Q8IYB4-2	2, PXR2a
Q8IYB4-3	3
Q8IYB4-4	4
Q8IYB4-5	5
Q8IYB4-6	6
Q8IYB4-7	7
Q8IYB4-8	8

RefSeq proteins (28): NP_001243679, NP_001243680, NP_001243681, NP_001243682, NP_001243683, NP_001243684, NP_001243685, NP_001336315, NP_001336316, NP_001336317, NP_001336318, NP_001336319, NP_001336320, NP_001336321, NP_001336322, NP_001336323, NP_001336324, NP_001336325, NP_001336326, NP_001336327, NP_001336328, NP_001336330, NP_001336333, NP_001336335, NP_001336337, NP_001336338, NP_001336339, NP_057643* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR024111	PEX5/PEX5L	Family

Pfam: PF13181, PF13432

UniProt features (32 total): splice variant 7, repeat 6, modified residue 6, sequence conflict 6, region of interest 3, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYB4-F1	63.53	0.39

Functional residue map

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

Post-translational modifications (6): 205, 253, 257, 261, 445, 447

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOMF_GTPASE_BINDING, chr3q26, TCF11_01, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, AACTTT_UNKNOWN, GOBP_PEROXISOMAL_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOCC_MICROBODY_MEMBRANE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, CTGYNNCTYTAA_UNKNOWN, TTTGCAC_MIR19A_MIR19B, GOBP_TRANSMEMBRANE_TRANSPORT, YGCGYRCGC_UNKNOWN

GO Biological Process (1): protein import into peroxisome matrix, docking (GO:0016560)

GO Molecular Function (4): peroxisome signal sequence receptor activity (GO:0000268), peroxisome matrix targeting signal-1 binding (GO:0005052), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (5): peroxisomal membrane (GO:0005778), cytosol (GO:0005829), signaling receptor complex (GO:0043235), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein localization	1
protein import into peroxisome matrix	1
signal sequence receptor activity	1
peroxisome signal sequence receptor activity	1
GTPase binding	1
binding	1
peroxisome	1
microbody membrane	1
cytoplasm	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1201 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX5L	PEX14	O75381	979
PEX5L	PEX7	O00628	967
PEX5L	RAB8B	Q92930	933
PEX5L	PEX6	Q13608	908
PEX5L	PEX12	O00623	906
PEX5L	PEX16	Q9Y5Y5	900
PEX5L	PEX19	P40855	897
PEX5L	PEX10	O60683	895
PEX5L	PEX3	P56589	894
PEX5L	PEX13	Q92968	888
PEX5L	PEX1	O43933	882
PEX5L	PEX2	P28328	856
PEX5L	PEX26	Q7Z412	813
PEX5L	AGPS	O00116	808
PEX5L	TRIM37	O94972	738

IntAct

13 interactions, top by confidence:

A	B	Type	Score
Pex14	PEX5L	psi-mi:“MI:0407”(direct interaction)	0.440
PEX5L	VIM	psi-mi:“MI:0915”(physical association)	0.400
PEX5L	KRT8	psi-mi:“MI:0915”(physical association)	0.400
PEX5L	KRT18	psi-mi:“MI:0915”(physical association)	0.400
PEX5L	RPS25	psi-mi:“MI:0915”(physical association)	0.400
PEX5L	USP20	psi-mi:“MI:0915”(physical association)	0.400
PEX5L		psi-mi:“MI:0915”(physical association)	0.370
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PEX5L (Two-hybrid), HCN1 (Reconstituted Complex), PEX5L (Proximity Label-MS), PEX5L (Proximity Label-MS), PEX5L (Proximity Label-MS), PEX5L (Proximity Label-MS), PEX5 (Negative Genetic), PEX5L (Affinity Capture-MS), NCL (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1L8FDW4, A4QP73, A4UMC5, B4NYQ2, B5X0I6, C4R2L0, D4A6D7, O09012, O70525, O74711, P33292, P50542, Q01495, Q1RMV0, Q29RR5, Q2M2R8, Q2TXF0, Q54MD1, Q5AV00, Q5F259, Q5R4F4, Q5U2Y6, Q5ZMQ9, Q6BM14, Q6CT48, Q6DI35, Q6DKK2, Q6FM42, Q6K687, Q6PD24, Q6ZTN6, Q752X0, Q80UP5, Q86YJ7, Q8C437, Q8CC21, Q8IYB4, Q8IZ07, Q8L611, Q920N5

Diamond homologs: A0A1L8FDW4, C4R2L0, O09012, O70525, O74711, O94325, P33292, P35056, P50542, Q01495, Q1RMV0, Q2M2R8, Q5ZMQ9, Q6BM14, Q6CT48, Q6FM42, Q752X0, Q8C437, Q8IYB4, Q920N5, Q925N3, Q99144, Q9FMA3, Q04364, Q54MD1, P17883, Q6ZXV5, O94474

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4032 predictions. Top by Δscore:

Variant	Effect	Δscore
3:179808433:CAGAG:C	acceptor_gain	1.0000
3:179808434:AGAG:A	acceptor_gain	1.0000
3:179808434:AGAGC:A	acceptor_gain	1.0000
3:179808435:GAG:G	acceptor_gain	1.0000
3:179808435:GAGCT:G	acceptor_gain	1.0000
3:179808436:AG:A	acceptor_gain	1.0000
3:179808436:AGC:A	acceptor_gain	1.0000
3:179808437:GCTA:G	acceptor_gain	1.0000
3:179808438:C:CC	acceptor_gain	1.0000
3:179808438:CTACA:C	acceptor_gain	1.0000
3:179808439:T:A	acceptor_gain	1.0000
3:179809474:T:C	donor_gain	1.0000
3:179809489:G:C	donor_gain	1.0000
3:179809664:AGCAC:A	acceptor_gain	1.0000
3:179809665:GCAC:G	acceptor_gain	1.0000
3:179809666:CAC:C	acceptor_gain	1.0000
3:179809666:CACC:C	acceptor_gain	1.0000
3:179809667:AC:A	acceptor_gain	1.0000
3:179809668:CC:C	acceptor_gain	1.0000
3:179809669:C:CC	acceptor_gain	1.0000
3:179811789:AGCTT:A	donor_gain	1.0000
3:179811790:G:C	donor_gain	1.0000
3:179811793:T:TA	donor_gain	1.0000
3:179815862:T:TA	donor_gain	1.0000
3:179815895:T:TA	donor_gain	1.0000
3:179819977:C:CC	acceptor_gain	1.0000
3:179859057:GTTA:G	donor_loss	1.0000
3:179859058:TTA:T	donor_loss	1.0000
3:179859059:TA:T	donor_loss	1.0000
3:179859060:AC:A	donor_loss	1.0000

AlphaMissense

4092 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:179801928:A:G	L594P	1.000
3:179802003:A:G	L569P	1.000
3:179802006:G:T	A568D	1.000
3:179802012:A:G	L566P	1.000
3:179807697:G:C	S551R	1.000
3:179807697:G:T	S551R	1.000
3:179807699:T:G	S551R	1.000
3:179807704:C:A	G549V	1.000
3:179807704:C:T	G549E	1.000
3:179807705:C:G	G549R	1.000
3:179807705:C:T	G549R	1.000
3:179807707:A:G	L548P	1.000
3:179807709:G:C	N547K	1.000
3:179807709:G:T	N547K	1.000
3:179807711:T:C	N547D	1.000
3:179807727:G:C	F541L	1.000
3:179807727:G:T	F541L	1.000
3:179807729:A:G	F541L	1.000
3:179807746:A:G	L535P	1.000
3:179807759:A:G	Y531H	1.000
3:179807770:G:T	A527D	1.000
3:179807771:C:G	A527P	1.000
3:179807806:C:A	G515V	1.000
3:179807806:C:T	G515E	1.000
3:179807807:C:A	G515W	1.000
3:179807807:C:G	G515R	1.000
3:179807807:C:T	G515R	1.000
3:179807809:A:G	L514P	1.000
3:179807812:C:G	R513P	1.000
3:179807819:A:G	W511R	1.000

dbSNP variants (sampled 300 via entrez): RS1000015485 (3:179900079 T>C), RS1000041217 (3:179957110 A>C), RS1000041308 (3:179938865 A>C), RS1000066797 (3:180017817 C>T), RS1000109632 (3:179914513 G>A,T), RS1000124264 (3:179803239 C>T), RS1000136389 (3:179824171 G>A), RS1000150918 (3:179999561 T>C), RS1000154726 (3:179869088 T>C), RS1000158269 (3:179824353 C>A,T), RS1000160580 (3:180013104 T>G), RS1000179313 (3:179920100 G>A), RS1000204583 (3:179874481 T>G), RS1000206639 (3:179963742 C>T), RS1000214217 (3:179855950 T>G)

Disease associations

OMIM: gene MIM:611058 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001033_9	Type 2 diabetes	7.000000e-06
GCST002726_21	Glucose homeostasis traits	2.000000e-06
GCST004286_3	Midgestational circulating levels of PBDEs (fetal genetic effect)	8.000000e-07
GCST004764_4	LDL cholesterol change in response to fenofibrate in statin-treated type 2 diabetes	7.000000e-07
GCST004765_23	Total cholesterol change in response to fenofibrate in statin-treated type 2 diabetes	1.000000e-07
GCST008103_127	Bipolar disorder	2.000000e-06
GCST90002409_38	Childhood body mass index	3.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006831	acute insulin response measurement
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0007806	total cholesterol change measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

112 measured of 112 human assays (112 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(diaminomethylideneamino)ethyl]-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	1400 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-methoxynaphthalen-1-yl)methyl]-1-[2-(methylamino)ethyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	1750 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-imidazol-1-ylethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	1920 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-aminoethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	1980 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-1-[2-(propan-2-ylamino)ethyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	2270 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-[2-[(1-hydroxy-2-methylpropan-2-yl)amino]ethyl]-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	2730 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(azetidin-3-yl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	3440 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-[2-(dimethylamino)ethyl]-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	4210 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-aminoethyl)-5-[(4-methoxy-5,6,7,8-tetrahydronaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	4620 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-methoxynaphthalen-1-yl)methyl]-1-(2-morpholin-4-ylethyl)-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	6720 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-1-phenyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	7610 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	7920 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	8710 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-benzyl-1-methyl-5-(4,5,6,7-tetrahydro-1,2-benzoxazol-3-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	9690 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-aminoethyl)-5-[(4-chlorophenyl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	10000 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-5-[(4-phenylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	10400 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-benzyl-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	10500 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(3-amino-2-hydroxypropyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	10600 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-cyclopentyl-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	10600 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-cyclobutyl-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	11100 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-aminoethyl)-5-[(3,4-dichlorophenyl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	11600 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-1-pyrazin-2-yl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	11900 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-5-[(3-phenylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	12700 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-1,2,3,3a,4,6,7,7a-octahydropyrazolo[4,3-c]pyridine-3-carboxamide	EC50	16500 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-benzyl-5-(1H-indol-3-ylmethyl)-1-phenyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	18300 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-[(7-methoxy-1H-indol-3-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	18900 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
12-[(4-methoxynaphthalen-1-yl)methyl]-4-(naphthalen-1-ylmethyl)-4,7,8,12-tetrazatricyclo[7.4.0.02,7]trideca-1,8-dien-3-one	EC50	19200 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(1H-indol-4-ylmethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	20200 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
methyl 3-[[1-(2-hydroxyethyl)-3-(naphthalen-1-ylmethylcarbamoyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]methyl]-1H-indole-7-carboxylate	EC50	21400 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-benzyl-1-methyl-5-[(6-phenylmethoxy-1H-indol-3-yl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	22100 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(quinolin-8-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	24100 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-[(6-methoxy-1H-indol-3-yl)methyl]-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	25000 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(3,4-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	26500 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-(1H-indol-3-ylmethyl)-1-methyl-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	27200 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-benzyl-1-methyl-5-[(4-phenylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	27800 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-[(3-fluoronaphthalen-1-yl)methyl]-1-(2-hydroxyethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	28700 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-5-[(4-propan-2-ylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	28900 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-benzyl-1-(2-hydroxyethyl)-5-(phenanthren-9-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	29800 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-5-[[4-(trifluoromethoxy)phenyl]methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	32300 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-5-[(4-propylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	32500 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
N-benzyl-1-methyl-5-[(3-phenylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	33600 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-5-[[4-(trifluoromethyl)phenyl]methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	34000 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-(1H-indol-3-ylmethyl)-1-methyl-N-(naphthalen-2-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	35200 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-chlorophenyl)methyl]-1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	36200 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-[(3-methylphenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	38100 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
methyl 3-[[1-(2-hydroxyethyl)-3-(naphthalen-1-ylmethylcarbamoyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]methyl]-1H-indole-6-carboxylate	EC50	38700 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-(1H-indol-2-ylmethyl)-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	38700 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-(2-hydroxyethyl)-5-(1H-indol-7-ylmethyl)-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	39800 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
5-[(4-ethoxyphenyl)methyl]-1-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	40000 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy
1-methyl-N,5-bis(naphthalen-1-ylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide	EC50	41800 nM	US-10138242: Pyrazolopyridine derivatives and their use in therapy

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
kojic acid	decreases expression	1
arsenite	affects binding, decreases reaction	1
entinostat	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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