PEX14

Summary

PEX14 (peroxisomal biogenesis factor 14, HGNC:8856) is a protein-coding gene on chromosome 1p36.22, encoding Peroxisomal membrane protein PEX14 (O75381). Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.

This gene encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. A mutation in this gene results in one form of Zellweger syndrome.

Source: NCBI Gene 5195 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 26
• Clinical variants (ClinVar): 500 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 106
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8856
Approved symbol	PEX14
Name	peroxisomal biogenesis factor 14
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142655
Ensembl biotype	protein_coding
OMIM	601791
Entrez	5195

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000356607, ENST00000472851, ENST00000491661, ENST00000492696, ENST00000889279, ENST00000889280, ENST00000923290, ENST00000923291

RefSeq mRNA: 1 — MANE Select: NM_004565 NM_004565

CCDS: CCDS30582

Canonical transcript exons

ENST00000356607 — 9 exons

Exon	Start	End
ENSE00000955670	10623019	10623121
ENSE00000955671	10624340	10624437
ENSE00000955672	10627272	10627363
ENSE00001472541	10629531	10630758
ENSE00001472556	10474950	10475002
ENSE00002820780	10618332	10618417
ENSE00002911510	10536213	10536297
ENSE00003509237	10599238	10599366
ENSE00003594889	10495274	10495321

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 91.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.1296 / max 120.3700, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
591	25.0901	1819
597	0.0394	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	91.53	gold quality
epithelium of bronchus	UBERON:0002031	91.19	gold quality
bronchus	UBERON:0002185	90.90	gold quality
parotid gland	UBERON:0001831	89.59	gold quality
right lobe of liver	UBERON:0001114	89.21	gold quality
pancreatic ductal cell	CL:0002079	89.09	gold quality
prefrontal cortex	UBERON:0000451	88.97	gold quality
urinary bladder	UBERON:0001255	88.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.14	gold quality
endothelial cell	CL:0000115	88.02	gold quality
oocyte	CL:0000023	87.78	gold quality
right frontal lobe	UBERON:0002810	87.76	gold quality
lower esophagus mucosa	UBERON:0035834	87.53	gold quality
cervix squamous epithelium	UBERON:0006922	87.38	gold quality
apex of heart	UBERON:0002098	87.31	gold quality
prostate gland	UBERON:0002367	87.26	gold quality
pigmented layer of retina	UBERON:0001782	87.23	gold quality
primary visual cortex	UBERON:0002436	87.08	gold quality
gastrocnemius	UBERON:0001388	87.03	gold quality
sural nerve	UBERON:0015488	87.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.91	gold quality
liver	UBERON:0002107	86.88	gold quality
saphenous vein	UBERON:0007318	86.85	gold quality
muscle of leg	UBERON:0001383	86.69	gold quality
frontal cortex	UBERON:0001870	86.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.55	gold quality
neocortex	UBERON:0001950	86.52	gold quality
nucleus accumbens	UBERON:0001882	86.45	gold quality
cingulate cortex	UBERON:0003027	86.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.11
E-CURD-112	yes	3.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

43 targeting PEX14, 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-4283	100.00	66.42	2097
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4481	100.00	66.42	1669
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-4745-5P	99.98	65.95	1028
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-10399-5P	99.17	69.87	2610

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 16)

• Serves as a transcriptional corepressor in addition to its peroxisomal function. (PMID:11863372)
• peroxisomal localization of Pex14p is affected by Pex13p (PMID:14715663)
• a new complementation group of the peroxisome biogenesis disorders with PEX14 as the defective gene (PMID:15146459)
• This report represents the second PEX14-deficiency associated with Zellweger syndrome and the first documentation of a PEX14-deficient patient with detailed clinical follow-up and biochemical, morphological, and radiological data. (PMID:18285423)
• N-terminal domain of Pex14, Pex14(N), adopts a three-helical fold. Pex5 and Pex19 ligand helices bind competitively to the same surface in Pex14(N) albeit with opposite directionality. (PMID:19197237)
• analysis of the human Pex5.Pex14.PTS1 protein complex structure obtained by small angle X-ray scattering (PMID:19584060)
• PEX14 is a multi-tasking protein that not only facilitates peroxisomal protein import but is also required for peroxisome motility by serving as membrane anchor for microtubules. (PMID:21525035)
• interaction of PEX5 with catalase and PEX14 (PMID:21976670)
• The novel Pex14-binding site may represent the initial tethering site of Pex5 from which the cargo-loaded receptor is further processed in a sequential manner. (PMID:24235149)
• PEX14 is the 13th PEX gene responsible for peroxisome biogenesis disorders. Thus far, only two patients with PEX14 deficiency have been reported. (PMID:26627464)
• data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. (PMID:27311714)
• Data suggest that soluble/cytosolic PEX5 interacts with PEX14/PEX13 complex, a model for the docking/translocation module (DTM) of the peroxisomal matrix protein translocon; PEX14/PEX13 complex appears to function in peroxisomal membrane as large cavity into which cytosolic PEX5 can enter to release its cargo. (PEX = peroxisomal biogenesis factor) (PMID:28765278)
• Mitotic phosphorylation of Pex14p regulates peroxisomal import machinery. (PMID:32854114)
• Competitive Microtubule Binding of PEX14 Coordinates Peroxisomal Protein Import and Motility. (PMID:33484719)
• Autosomal dominant Zellweger spectrum disorder caused by de novo variants in PEX14 gene. (PMID:37493040)
• Overexpression of PEX14 results in mistargeting to mitochondria, accompanied by organelle fragmentation and clustering in human embryonic kidney cells. (PMID:38762172)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex14	ENSDARG00000028322
mus_musculus	Pex14	ENSMUSG00000028975
rattus_norvegicus	Pex14	ENSRNOG00000013498
drosophila_melanogaster	Pex14	FBGN0037020
caenorhabditis_elegans		WBGENE00004199

Protein

Protein identifiers

Peroxisomal membrane protein PEX14 — O75381 (reviewed: O75381)

Alternative names: PTS1 receptor-docking protein, Peroxin-14, Peroxisomal membrane anchor protein PEX14

All UniProt accessions (2): O75381, K7EK59

UniProt curated annotations — full annotation on UniProt →

Function. Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor. The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm. Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix. Plays a key role for peroxisome movement through a direct interaction with tubulin.

Subunit / interactions. Interacts with PEX13; forming the PEX13-PEX14 docking complex. Interacts with PEX5 (via WxxxF/Y motifs). Interacts with PEX19. Interacts with tubulin.

Subcellular location. Peroxisome membrane.

Disease relevance. Peroxisome biogenesis disorder complementation group K (PBD-CGK) [MIM:614887] A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). The disease is caused by variants affecting the gene represented in this entry. Peroxisome biogenesis disorder 13A (PBD13A) [MIM:614887] A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peroxin-14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75381-1	1	yes
O75381-2	2

RefSeq proteins (1): NP_004556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006785	Pex14_N	Domain
IPR025655	PEX14	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily

Pfam: PF04695

UniProt features (29 total): compositionally biased region 5, modified residue 5, helix 4, sequence variant 3, topological domain 2, mutagenesis site 2, region of interest 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1, strand 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2W84	SOLUTION NMR
2W85	SOLUTION NMR
4BXU	SOLUTION NMR
9GAG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75381-F1	68.48	0.31

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 (5): 2, 34, 232, 282, 335

Mutagenesis-validated functional residues (2):

Position	Phenotype
52	reduced interaction with pex19, minor effect on interaction with pex5.
56	reduced interaction with pex19, minor effect on interaction with pex5.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9033241	Peroxisomal protein import
R-HSA-9603798	Class I peroxisomal membrane protein import

MSigDB gene sets: 387 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MICROTUBULE_ANCHORING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_BINDING, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_PEROXISOMAL_TRANSPORT, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (16): peroxisome organization (GO:0007031), protein import into peroxisome matrix (GO:0016558), protein import into peroxisome matrix, docking (GO:0016560), protein import into peroxisome matrix, translocation (GO:0016561), negative regulation of protein binding (GO:0032091), microtubule anchoring (GO:0034453), cellular response to reactive oxygen species (GO:0034614), peroxisome transport along microtubule (GO:0036250), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), protein import into peroxisome matrix, substrate release (GO:0044721), negative regulation of DNA-templated transcription (GO:0045892), protein-containing complex assembly (GO:0065003), protein monoubiquitination (GO:0006513), protein transport (GO:0015031), protein import into peroxisome matrix, receptor recycling (GO:0016562), protein unfolding (GO:0043335)

GO Molecular Function (8): transcription corepressor activity (GO:0003714), signaling receptor binding (GO:0005102), microtubule binding (GO:0008017), transmembrane protein transporter activity (GO:0008320), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (8): fibrillar center (GO:0001650), nucleus (GO:0005634), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), protein-containing complex (GO:0032991), peroxisomal importomer complex (GO:1990429)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	2
Protein ubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein import into peroxisome matrix	4
protein binding	4
cellular anatomical structure	3
intracellular protein localization	2
tubulin binding	2
organelle organization	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
protein localization to peroxisome	1
establishment of protein localization to peroxisome	1
intracellular protein transmembrane transport	1
regulation of protein binding	1
negative regulation of binding	1
microtubule cytoskeleton organization	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
organelle transport along microtubule	1
protein-containing complex disassembly	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cellular component assembly	1
protein-containing complex organization	1
protein ubiquitination	1
transport	1
establishment of protein localization	1
receptor recycling	1
cellular process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
molecular adaptor activity	1
binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
microbody	1
peroxisome	1

Protein interactions and networks

STRING

804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX14	PEX13	Q92968	999
PEX14	PEX5	P50542	999
PEX14	PEX7	O00628	989
PEX14	PEX12	O00623	983
PEX14	PEX5L	Q8IYB4	979
PEX14	PEX19	P40855	969
PEX14	PEX3	P56589	953
PEX14	PEX2	P28328	951
PEX14	PEX10	O60683	946
PEX14	PEX6	Q13608	931
PEX14	PEX16	Q9Y5Y5	922
PEX14	PEX26	Q7Z412	854
PEX14	AGPS	O00116	828
PEX14	PEX1	O43933	789
PEX14	PEX11A	O75192	746

IntAct

158 interactions, top by confidence:

A	B	Type	Score
PEX14	PEX19	psi-mi:“MI:2364”(proximity)	0.950
PEX14	PEX19	psi-mi:“MI:0915”(physical association)	0.950
PEX19	PEX14	psi-mi:“MI:0915”(physical association)	0.950
PEX19	PEX14	psi-mi:“MI:0407”(direct interaction)	0.950
PEX14	PEX19	psi-mi:“MI:0914”(association)	0.950
PEX14	PEX19	psi-mi:“MI:0407”(direct interaction)	0.950

BioGRID (311): PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Co-fractionation), PEX14 (Proximity Label-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), PEX14 (Affinity Capture-MS)

ESM2 similar proteins: A7YVI8, F1QCY8, F5HB62, F5HF68, O75381, O95343, P03177, P0C8B5, P36552, P53814, P97287, Q02873, Q07820, Q0IH40, Q1HVD1, Q29RJ0, Q3B7D0, Q3KSQ2, Q3UHD9, Q4VC12, Q5BIR3, Q5BKU9, Q5E9N0, Q5R4R7, Q5R7Q6, Q5XIX0, Q62233, Q642G4, Q6BCB4, Q6DGF9, Q6Y2X3, Q7L2J0, Q7YRZ9, Q80TL4, Q89420, Q8CGU4, Q8CI12, Q8HYS5, Q8K3A9, Q921R4

Diamond homologs: O60065, O75381, P53112, P78723, Q642G4, Q9R0A0, Q9Z2Z3, Q54C55, Q9HG09, Q9FXT6, Q9FM14

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PEX14	“up-regulates activity”	PEX5	binding
PEX14	“up-regulates activity”	PEX7	binding
PEX14	“up-regulates activity”	PEX13	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peroxisomal protein import	11	24.1×	3e-10
Protein localization	5	12.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	205
Likely benign	198
Benign	24

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1453475	NC_000001.10:g.(?10535024)(10596374_?)del	Pathogenic
2425163	NC_000001.10:g.(?10535024)(10535079_?)del	Pathogenic
2425165	NC_000001.10:g.(?10535024)(10687440_?)del	Pathogenic
2753909	NM_004565.3(PEX14):c.109C>T (p.Gln37Ter)	Pathogenic
3247784	NC_000001.10:g.(?10596250)(10596374_?)del	Pathogenic
3663959	NC_000001.11:g.10599291_10599292insTAAAGCAGCAATAAACTCAAGGATAAATTAAGGAAATTGAATGAGCCACATTTGGAAGCAGTGTTGAGGCTAATATTCTGTCGCTTAAGGTTAAATTGCAACTGAGAGAGGTTCCGGAGAATCTGAAATCGGGGAGGCAACTTACTAGGATGCGAGGCATTCTGTGGCTGTAAAGGTCTTTGCTCAGTGAAGATTCTGTTGCAGCTATGGACACTGACAAAAGGTACTCACCTGCAATGATGTCCTCTTCTCCCCAGGGCTGACAGATGAAGAGATTGATATGGCCTTCCAGCAGTCGGGCACTGCTGCCG	Pathogenic
7702	NG_008340.2:g.(25377_66267)_(66353_129292)del	Pathogenic
2709504	NM_004565.3(PEX14):c.204_298+125delinsTATTCCTT	Likely pathogenic
2769432	NM_004565.3(PEX14):c.299-5_306del	Likely pathogenic
2967272	NM_004565.3(PEX14):c.298+1G>C	Likely pathogenic
862190	NM_004565.3(PEX14):c.36+1G>T	Likely pathogenic

SpliceAI

3103 predictions. Top by Δscore:

Variant	Effect	Δscore
1:10472321:AC:A	donor_gain	1.0000
1:10472322:CC:C	donor_gain	1.0000
1:10472329:T:TA	donor_gain	1.0000
1:10475002:GGTAA:G	donor_loss	1.0000
1:10475003:G:C	donor_loss	1.0000
1:10475004:T:A	donor_loss	1.0000
1:10495318:GCTG:G	donor_gain	1.0000
1:10599367:G:GG	donor_gain	1.0000
1:10618327:TGTA:T	acceptor_loss	1.0000
1:10618330:A:AG	acceptor_gain	1.0000
1:10618331:G:GG	acceptor_gain	1.0000
1:10618416:AGGTG:A	donor_loss	1.0000
1:10618418:G:C	donor_loss	1.0000
1:10618418:G:GG	donor_gain	1.0000
1:10623117:GACAG:G	donor_gain	1.0000
1:10629526:TCTA:T	acceptor_loss	1.0000
1:10629528:TA:T	acceptor_loss	1.0000
1:10629529:A:AG	acceptor_gain	1.0000
1:10629529:A:T	acceptor_loss	1.0000
1:10629530:G:GC	acceptor_loss	1.0000
1:10629530:G:GG	acceptor_gain	1.0000
1:10629530:GGA:G	acceptor_gain	1.0000
1:10472330:C:CA	donor_gain	0.9900
1:10472334:AGGT:A	donor_gain	0.9900
1:10472335:G:C	donor_gain	0.9900
1:10472340:T:TA	donor_gain	0.9900
1:10474998:GCCAG:G	donor_gain	0.9900
1:10495272:A:AG	acceptor_gain	0.9900
1:10495273:G:GG	acceptor_gain	0.9900
1:10495273:GCCAA:G	acceptor_gain	0.9900

AlphaMissense

2452 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:10536231:T:C	F35L	1.000
1:10536232:T:C	F35S	1.000
1:10536233:T:A	F35L	1.000
1:10536233:T:G	F35L	1.000
1:10536282:T:C	F52L	1.000
1:10536284:C:A	F52L	1.000
1:10536284:C:G	F52L	1.000
1:10536223:C:A	A32E	0.999
1:10536232:T:G	F35C	0.999
1:10536235:T:C	L36P	0.999
1:10536283:T:C	F52S	0.999
1:10536283:T:G	F52C	0.999
1:10536286:T:A	L53Q	0.999
1:10536286:T:C	L53P	0.999
1:10599241:T:C	L58P	0.999
1:10627346:A:C	K220N	0.999
1:10627346:A:T	K220N	0.999
1:10629574:T:A	W241R	0.999
1:10629574:T:C	W241R	0.999
1:10627321:T:C	L212P	0.998
1:10627338:T:C	S218P	0.998
1:10627342:T:C	L219S	0.998
1:10627351:T:C	L222P	0.998
1:10627354:T:C	L223P	0.998
1:10629538:T:C	F229L	0.998
1:10629540:C:A	F229L	0.998
1:10629540:C:G	F229L	0.998
1:10629576:G:C	W241C	0.998
1:10629576:G:T	W241C	0.998
1:10536250:T:A	V41D	0.997

dbSNP variants (sampled 300 via entrez): RS1000011195 (1:10551492 T>A), RS1000028855 (1:10482560 A>G), RS1000038150 (1:10614960 G>A), RS1000053629 (1:10536048 G>A), RS1000061908 (1:10548249 A>C), RS1000076500 (1:10537984 G>A,C), RS1000077966 (1:10482260 C>T), RS1000090072 (1:10514679 A>G), RS1000125239 (1:10557947 A>T), RS1000140380 (1:10505931 T>C), RS1000144971 (1:10572504 C>T), RS1000160346 (1:10539534 C>T), RS1000167270 (1:10624265 G>A,T), RS1000177990 (1:10588232 A>G), RS1000180686 (1:10591460 A>G)

Disease associations

OMIM: gene MIM:601791 | disease phenotypes: MIM:614887

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 13A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Definitive	Autosomal recessive
Zellweger spectrum disorders	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
peroxisome biogenesis disorder	Definitive	AR

Mondo (4): peroxisome biogenesis disorder, complementation group K (MONDO:0800365), peroxisome biogenesis disorder 13A (Zellweger) (MONDO:0013952), peroxisome biogenesis disorder (MONDO:0019234), Zellweger spectrum disorders (MONDO:0019609)

Orphanet (1): Zellweger syndrome (Orphanet:912)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000658_4	Optic nerve measurement (rim area)	7.000000e-06
GCST001930_8	Breast cancer	1.000000e-08
GCST001937_46	Breast cancer	2.000000e-10
GCST002083_10	Self-reported allergy	4.000000e-07
GCST002606_26	Prostate cancer	2.000000e-08
GCST003842_3	Breast cancer (estrogen-receptor negative)	2.000000e-09
GCST003845_1	Breast cancer	5.000000e-10
GCST003985_6	Breast size	2.000000e-07
GCST003987_27	Asthma	3.000000e-08
GCST004988_187	Breast cancer	5.000000e-20
GCST005235_3	Hand grip strength	6.000000e-11
GCST006612_100	LDL cholesterol	3.000000e-09
GCST006614_137	Total cholesterol levels	9.000000e-09
GCST006661_184	Male-pattern baldness	3.000000e-10
GCST006661_55	Male-pattern baldness	3.000000e-09
GCST006661_56	Male-pattern baldness	4.000000e-09
GCST006979_852	Heel bone mineral density	9.000000e-13
GCST006988_196	Blond vs. brown/black hair color	1.000000e-08
GCST007656_15	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	4.000000e-18
GCST009391_2020	Metabolite levels	5.000000e-06
GCST009464_23	Facial morphology	6.000000e-09
GCST010002_376	Refractive error	2.000000e-09
GCST010042_93	Asthma	7.000000e-11
GCST010043_78	Asthma	8.000000e-13
GCST012490_274	Femur bone mineral density x serum urate levels interaction	3.000000e-09
GCST90014325_2	Asthma	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0010348	cholesteryl ester 20:4 measurement
EFO:0004531	urate measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D015211	Zellweger Syndrome	C06.552.970; C10.228.140.163.100.968; C12.050.351.968.419.978; C12.200.777.419.978; C12.950.419.978; C16.131.077.970; C16.320.565.189.968; C16.320.565.663.970; C18.452.132.100.968; C18.452.648.189.968; C18.452.648.663.970
C566624	Peroxisome Biogenesis Disorder, Complementation Group K (supp.)
C536664	Peroxisome biogenesis disorders (supp.)
C531857	Zellweger leukodystrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523152 (SINGLE PROTEIN)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 27 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.46	EC50	3480	nM	CHEMBL4591370
5.36	EC50	4380	nM	CHEMBL4579832
5.14	EC50	7250	nM	CHEMBL4531733
5.10	EC50	7890	nM	CHEMBL4476039
5.06	EC50	8690	nM	CHEMBL4571686
5.03	EC50	9310	nM	CHEMBL4531560
5.03	EC50	9310	nM	CHEMBL4548156
5.02	EC50	9550	nM	CHEMBL4443867

PubChem BioAssay actives

8 with measured affinity, of 65 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[2-[(1-hydroxy-2-methylpropan-2-yl)amino]ethyl]-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-4,6-dihydropyrrolo[3,4-d]pyrazole-3-carboxamide	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	3.4800	uM
1-(2-aminoethyl)-5-[(4-methoxynaphthalen-1-yl)methyl]-N-(naphthalen-1-ylmethyl)-4,6-dihydropyrrolo[3,4-d]pyrazole-3-carboxamide	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	4.3800	uM
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	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	7.2500	uM
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	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	7.8900	uM
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	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	8.6900	uM
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	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	9.3100	uM
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	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	9.3100	uM
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	1582244: Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	ec50	9.5500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases methylation, decreases expression	2
Valproic Acid	decreases methylation, affects expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
UF010 compound	increases acetylation	1
FR900359	decreases phosphorylation	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	affects methylation	1
coumarin	increases phosphorylation	1
butylparaben	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, increases expression	1
Citrinin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Mercury	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4380601	ADMET	Inhibition of biotinylated PEX5-derived ALSENWAQEFLA binding to human N-terminal His-tagged PEX14 (21 to 84 residues) expressed in Escherichia coli BL21 by Alphascreen assay	Structure-Activity Relationship in Pyrazolo[4,3-c]pyridines, First Inhibitors of PEX14-PEX5 Protein-Protein Interaction with Trypanocidal Activity. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
NCT03440905	Not specified	COMPLETED	Proxy-Reported Symptoms and Quality of Life Survey in Zellweger Spectrum Disorders
NCT06190626	Not specified	RECRUITING	Longitudinal Prospective Natural History Study of Retinopathy in Zellweger Spectrum Disorder
NCT00004442	Not specified	TERMINATED	Study of Bile Acids in Patients With Peroxisomal Disorders
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project