PEX3

Summary

PEX3 (peroxisomal biogenesis factor 3, HGNC:8858) is a protein-coding gene on chromosome 6q24.2, encoding Peroxisomal biogenesis factor 3 (P56589). Involved in peroxisome biosynthesis and integrity.

The product of this gene is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause Zellweger syndrome (ZWS).

Source: NCBI Gene 8504 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 430 total — 21 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 106
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_003630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8858
Approved symbol	PEX3
Name	peroxisomal biogenesis factor 3
Location	6q24.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000034693
Ensembl biotype	protein_coding
OMIM	603164
Entrez	8504

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000367591, ENST00000367592, ENST00000585848, ENST00000918413, ENST00000918414, ENST00000951239

RefSeq mRNA: 1 — MANE Select: NM_003630 NM_003630

CCDS: CCDS5199

Canonical transcript exons

ENST00000367591 — 12 exons

Exon	Start	End
ENSE00000764853	143459085	143459216
ENSE00000764854	143462916	143462997
ENSE00000764855	143468122	143468165
ENSE00000764858	143470961	143471085
ENSE00000764860	143471383	143471449
ENSE00000764861	143471557	143471611
ENSE00001856565	143450805	143451115
ENSE00001896533	143489143	143490616
ENSE00002482561	143479076	143479198
ENSE00002500505	143474786	143474856
ENSE00002512118	143485152	143485248
ENSE00002733562	143472160	143472328

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6149 / max 102.7830, expressed in 1795 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70242	8.2364	1740
70241	3.2954	1500
70243	2.4831	1310
70240	1.0284	689
70244	0.5716	328

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.44	gold quality
endothelial cell	CL:0000115	95.56	gold quality
right adrenal gland cortex	UBERON:0035827	94.68	gold quality
right adrenal gland	UBERON:0001233	94.24	gold quality
adrenal cortex	UBERON:0001235	93.27	gold quality
left adrenal gland	UBERON:0001234	93.22	gold quality
left adrenal gland cortex	UBERON:0035825	93.00	gold quality
adrenal gland	UBERON:0002369	92.80	gold quality
oocyte	CL:0000023	92.12	gold quality
upper leg skin	UBERON:0004262	91.55	gold quality
penis	UBERON:0000989	89.06	gold quality
renal medulla	UBERON:0000362	88.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.20	gold quality
mammalian vulva	UBERON:0000997	88.15	gold quality
right lobe of liver	UBERON:0001114	87.98	gold quality
nephron tubule	UBERON:0001231	87.86	gold quality
skin of hip	UBERON:0001554	87.82	gold quality
choroid plexus epithelium	UBERON:0003911	87.51	gold quality
secondary oocyte	CL:0000655	87.26	gold quality
calcaneal tendon	UBERON:0003701	87.11	gold quality
heart right ventricle	UBERON:0002080	87.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.86	gold quality
esophagus mucosa	UBERON:0002469	86.82	gold quality
bronchial epithelial cell	CL:0002328	86.62	gold quality
liver	UBERON:0002107	86.51	gold quality
upper arm skin	UBERON:0004263	86.33	gold quality
stromal cell of endometrium	CL:0002255	85.90	gold quality
cauda epididymis	UBERON:0004360	85.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.79	gold quality
prefrontal cortex	UBERON:0000451	85.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	322.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SEC16B

miRNA regulators (miRDB)

101 targeting PEX3, 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-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 19)

• Interaction of PEX3 and PEX19 visualized by fluorescence resonance energy transfer (FRET). (PMID:14713233)
• Results suggest that PEX3 plays a selective, essential, and direct role in class I peroxisomal membrane protein import as a docking factor for PEX19. (PMID:15007061)
• Data suggest that Pex19p probably functions as a chaperone for membrane proteins and transports them to peroxisomes by anchoring to Pex3p using residues 12-73 and 40-131. (PMID:16895967)
• either one or two tryptophan residues of Pex3p (Trp-104 and Trp-224) are directly involved in binding to Pex19p. (PMID:18174172)
• Pex3p follows the ER-to-peroxisomal route; Pex3p requires Pex16p for ER location but is dispensable for the ER location of Pex16p (PMID:19479899)
• The cytosolic domain of PEX3, a protein involved in the biogenesis of peroxisomes, binds membrane lipids. (PMID:19715730)
• The crystal structure of the cytosolic domain of PEX3 in complex with a PEX19-derived peptide. PEX3 adopts a novel fold that is best described as a large helical bundle. (PMID:20554521)
• The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis. (PMID:21102411)
• Mutations in the PEX19-binding domain of PEX3 reduce the affinity for PEX19 and destabilize PEX3. (PMID:22624858)
• PEX16 mediates the peroxisomal trafficking of two distinct peroxisomal membrane proteins, PEX3 and PMP34, via the endoplasmic reticulum (PMID:25002403)
• Thus within the cell, PEX3 is stabilized by PEX19 preventing PEX3 aggregation. (PMID:25062251)
• This insertion of PEX3 into the ER is physiologically relevant. (PMID:26572236)
• that newly synthesized UBXD8 is post-translationally inserted into discrete ER subdomains by a mechanism requiring cytosolic PEX19 and membrane-integrated PEX3, proteins hitherto exclusively implicated in peroxisome biogenesis (PMID:27295553)
• Thus, PEX19 and PEX3 peroxisome biogenesis factors provide an alternative posttranslational route for membrane insertion of the reticulon homology domain-containing proteins, implying that endoplasmic reticulum membrane shaping and peroxisome biogenesis may be coordinated. (PMID:29396426)
• BAG1, CHMP2B, PEX3, and WIPI1 confirmed a strong differential gene expression, in 355 melanoma samples. (PMID:30622661)
• studies indicate that Pex3 and Pex19 can also facilitate sorting of certain membrane proteins to other cellular organelles, including the endoplasmic reticulum, lipid droplets, and mitochondria (PMID:30776093)
• Quantitative Proteomics and Differential Protein Abundance Analysis after the Depletion of PEX3 from Human Cells Identifies Additional Aspects of Protein Targeting to the ER. (PMID:34884833)
• rs9390123 and rs9399451 influence the DNA repair capacity of lung cancer by regulating PEX3 and PHACTR2AS1 expression instead of PHACTR2. (PMID:35059740)
• Hypomorphic mutation of PEX3 with peroxisomal mosaicism reveals the oscillating nature of peroxisome biogenesis coupled with differential metabolic activities. (PMID:35932552)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pex3	ENSMUSG00000019809
rattus_norvegicus	Pex3	ENSRNOG00000015660

Protein

Protein identifiers

Peroxisomal biogenesis factor 3 — P56589 (reviewed: P56589)

Alternative names: Peroxin-3, Peroxisomal assembly protein PEX3

All UniProt accessions (2): P56589, Q7Z6V3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.

Subunit / interactions. Interacts with PEX19.

Subcellular location. Peroxisome membrane.

Tissue specificity. Found in all examined tissues.

Disease relevance. Peroxisome biogenesis disorder complementation group 12 (PBD-CG12) [MIM:614882] 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 10A (PBD10A) [MIM:614882] 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. Peroxisome biogenesis disorder 10B (PBD10B) [MIM:617370] A moderately severe peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD10B is characterized by neonatal jaundice, dysmorphic features, delayed psychomotor development, axial hypotonia that can progress to severe spastic paraparesis with hyperreflexia, nephrocalcinosis, neurogenic bladder, nystagmus, and cataracts. Laboratory studies show increased levels of very long-chain fatty acids. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peroxin-3 family.

RefSeq proteins (1): NP_003621* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006966	Peroxin-3	Family

Pfam: PF04882

UniProt features (33 total): helix 16, topological domain 3, sequence variant 3, strand 3, mutagenesis site 2, transmembrane region 2, region of interest 2, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3MK4	X-RAY DIFFRACTION	2.42
3AJB	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56589-F1	88.94	0.75

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
125	abolishes binding to pex19 without affecting targeting to peroxisomes; when associated with d-134.
134	abolishes binding to pex19 without affecting targeting to peroxisomes; when associated with p-125.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1369062	ABC transporters in lipid homeostasis
R-HSA-9603798	Class I peroxisomal membrane protein import

MSigDB gene sets: 432 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MORF_ATRX, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MAHAJAN_RESPONSE_TO_IL1A_DN, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, MORF_RAP1A, GOBP_PEROXISOMAL_TRANSPORT, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, FISCHER_DREAM_TARGETS, GOCC_MICROBODY_MEMBRANE, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (2): peroxisome organization (GO:0007031), protein import into peroxisome membrane (GO:0045046)

GO Molecular Function (3): lipid binding (GO:0008289), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), protein-containing complex (GO:0032991), protein-lipid complex (GO:0032994)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ABC-family protein mediated transport	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
organelle organization	1
intracellular protein transport	1
peroxisomal membrane transport	1
protein localization to membrane	1
protein localization to peroxisome	1
establishment of protein localization to peroxisome	1
establishment of protein localization to membrane	1
protein binding	1
molecular adaptor activity	1
nuclear lumen	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular_component	1
protein-containing complex	1

Protein interactions and networks

STRING

1501 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX3	PEX19	P40855	989
PEX3	PEX16	Q9Y5Y5	984
PEX3	PEX13	Q92968	976
PEX3	PEX6	Q13608	968
PEX3	PEX10	O60683	963
PEX3	PEX12	O00623	962
PEX3	PEX2	P28328	955
PEX3	PEX14	O75381	953
PEX3	PEX5	P50542	950
PEX3	PEX7	O00628	944
PEX3	PEX26	Q7Z412	926
PEX3	PEX5L	Q8IYB4	894
PEX3	PEX11B	O96011	859
PEX3	AGPS	O00116	855
PEX3	PEX11A	O75192	844

IntAct

120 interactions, top by confidence:

A	B	Type	Score
PEX19	PEX3	psi-mi:“MI:0915”(physical association)	0.980
PEX3	PEX19	psi-mi:“MI:0915”(physical association)	0.980
PEX19	PEX3	psi-mi:“MI:2364”(proximity)	0.980
PEX3	PEX19	psi-mi:“MI:2364”(proximity)	0.980

BioGRID (217): PEX3 (Two-hybrid), PEX3 (Affinity Capture-MS), PEX3 (Two-hybrid), PEX3 (Affinity Capture-MS), PEX19 (Two-hybrid), PEX3 (Affinity Capture-MS), PEX19 (FRET), PEX16 (Two-hybrid), PEX19 (Two-hybrid), PEX3 (Affinity Capture-Luminescence), PEX3 (Reconstituted Complex), PCBP1 (Proximity Label-MS), PEX3 (Affinity Capture-MS), PEX3 (Affinity Capture-MS), PEX3 (Proximity Label-MS)

ESM2 similar proteins: A2AF53, A4FV75, A4QNE0, A5A6S6, A6QL84, A6ZIQ8, D3ZEH5, E1BD52, O57425, O60337, P56589, P58749, Q0P5I8, Q0VC58, Q2TBU2, Q2V4F9, Q3T0J1, Q3TMP8, Q4R5B4, Q4R7G8, Q5JZQ8, Q5M8Y1, Q5R8H8, Q5REE3, Q5RF53, Q5XIK2, Q5ZK43, Q6GLK9, Q6IC98, Q6NRL4, Q6ZQ89, Q7L5D6, Q7SYC7, Q80YV4, Q8CIF6, Q8NBJ9, Q8NFB2, Q8VCM5, Q8VIJ8, Q93ZQ5

Diamond homologs: A6H7C2, O94227, P56589, Q60HE1, Q9JJK3, Q9JJK4, Q9QXY9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PEX3	“up-regulates activity”	PEX19	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
Class I peroxisomal membrane protein import	5	48.1×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
peroxisome organization	5	52.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	14
Uncertain significance	176
Likely benign	166
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1361900	NM_003630.3(PEX3):c.160C>T (p.Arg54Ter)	Pathogenic
1456893	NM_003630.3(PEX3):c.157C>T (p.Arg53Ter)	Pathogenic
1457724	NM_003630.3(PEX3):c.17G>A (p.Trp6Ter)	Pathogenic
1900608	NM_003630.3(PEX3):c.203_204dup (p.Val69fs)	Pathogenic
2120965	NM_003630.3(PEX3):c.360C>G (p.Tyr120Ter)	Pathogenic
2424711	NC_000006.11:g.(?143806269)(143806405_?)del	Pathogenic
2717279	NM_003630.3(PEX3):c.807_808del (p.Met270fs)	Pathogenic
2718950	NM_003630.3(PEX3):c.115_116del (p.Glu39fs)	Pathogenic
2752280	NM_003630.3(PEX3):c.745C>T (p.Gln249Ter)	Pathogenic
2800237	NM_003630.3(PEX3):c.227_228del (p.Leu76fs)	Pathogenic
3648454	NM_003630.3(PEX3):c.494T>G (p.Leu165Ter)	Pathogenic
3655590	NM_003630.3(PEX3):c.284dup (p.Asn95fs)	Pathogenic
390238	NM_003630.3(PEX3):c.898C>T (p.Arg300Ter)	Pathogenic
4722273	NM_003630.3(PEX3):c.699_700dup (p.Leu234fs)	Pathogenic
4724601	NM_003630.3(PEX3):c.863_864insAT (p.Phe288fs)	Pathogenic
4742849	NM_003630.3(PEX3):c.766C>T (p.Arg256Ter)	Pathogenic
596529	NM_003630.3(PEX3):c.331+2_331+5del	Pathogenic
598102	NM_003630.3(PEX3):c.856C>T (p.Arg286Ter)	Pathogenic
631556	NM_003630.3(PEX3):c.942-8T>G	Pathogenic
6618	NM_003630.3(PEX3):c.543dup (p.Val182fs)	Pathogenic
965193	NM_003630.3(PEX3):c.735del (p.Pro245_Leu246insTer)	Pathogenic
1065621	NM_003630.3(PEX3):c.844A>C (p.Thr282Pro)	Likely pathogenic
1324884	NM_003630.3(PEX3):c.130G>T (p.Glu44Ter)	Likely pathogenic
2432570	NM_003630.3(PEX3):c.332-2A>G	Likely pathogenic
2445860	NM_003630.3(PEX3):c.685G>T (p.Gly229Ter)	Likely pathogenic
2504000	NM_003630.3(PEX3):c.331+1G>C	Likely pathogenic
2627431	NM_003630.3(PEX3):c.144C>A (p.Tyr48Ter)	Likely pathogenic
2873216	NM_003630.3(PEX3):c.818+1G>A	Likely pathogenic
2980161	NM_003630.3(PEX3):c.942-1G>T	Likely pathogenic
3065043	NM_003630.3(PEX3):c.74G>T (p.Gly25Val)	Likely pathogenic

SpliceAI

1498 predictions. Top by Δscore:

Variant	Effect	Δscore
6:143459212:GACAG:G	donor_gain	1.0000
6:143459213:ACAGG:A	donor_loss	1.0000
6:143459214:CAGGT:C	donor_loss	1.0000
6:143459215:AGGTA:A	donor_loss	1.0000
6:143459216:GGTA:G	donor_loss	1.0000
6:143459217:G:C	donor_loss	1.0000
6:143459218:T:G	donor_loss	1.0000
6:143462902:T:TA	acceptor_gain	1.0000
6:143462906:T:A	acceptor_gain	1.0000
6:143462909:A:AG	acceptor_gain	1.0000
6:143462910:T:G	acceptor_gain	1.0000
6:143462912:ACAG:A	acceptor_loss	1.0000
6:143462912:ACAGT:A	acceptor_gain	1.0000
6:143462913:C:G	acceptor_gain	1.0000
6:143462913:CAG:C	acceptor_loss	1.0000
6:143462914:A:AC	acceptor_loss	1.0000
6:143462914:A:AG	acceptor_gain	1.0000
6:143462914:AGT:A	acceptor_gain	1.0000
6:143462915:G:GA	acceptor_gain	1.0000
6:143462915:GT:G	acceptor_gain	1.0000
6:143462915:GTG:G	acceptor_gain	1.0000
6:143462915:GTGC:G	acceptor_gain	1.0000
6:143462915:GTGCT:G	acceptor_gain	1.0000
6:143462998:GT:G	donor_loss	1.0000
6:143462999:T:G	donor_loss	1.0000
6:143470956:T:TA	acceptor_gain	1.0000
6:143470956:TGAA:T	acceptor_loss	1.0000
6:143470958:AAG:A	acceptor_loss	1.0000
6:143470959:A:AT	acceptor_loss	1.0000
6:143470960:G:GA	acceptor_loss	1.0000

AlphaMissense

2451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:143459165:G:C	A52P	0.999
6:143459172:G:C	R54P	0.999
6:143459183:T:C	F58L	0.999
6:143459185:T:A	F58L	0.999
6:143459185:T:G	F58L	0.999
6:143459196:A:C	Q62P	0.999
6:143468144:T:A	W104R	0.999
6:143468144:T:C	W104R	0.999
6:143468146:G:C	W104C	0.999
6:143468146:G:T	W104C	0.999
6:143468154:T:C	L107P	0.999
6:143470990:A:C	S121R	0.999
6:143470992:T:A	S121R	0.999
6:143470992:T:G	S121R	0.999
6:143471027:T:C	L133S	0.999
6:143471031:C:A	N134K	0.999
6:143471031:C:G	N134K	0.999
6:143471039:G:A	G137D	0.999
6:143471416:T:G	Y164D	0.999
6:143471420:T:C	L165S	0.999
6:143485178:C:A	A323D	0.999
6:143489197:T:C	F365L	0.999
6:143489199:T:A	F365L	0.999
6:143489199:T:G	F365L	0.999
6:143451115:G:A	G25R	0.998
6:143451115:G:C	G25R	0.998
6:143459169:G:C	R53P	0.998
6:143459180:C:G	H57D	0.998
6:143459205:G:A	C65Y	0.998
6:143459206:C:G	C65W	0.998

dbSNP variants (sampled 300 via entrez): RS1000018517 (6:143477339 C>T), RS1000070434 (6:143487887 T>C), RS1000241185 (6:143454192 C>G,T), RS1000259802 (6:143470010 T>C), RS1000294838 (6:143453760 A>G), RS1000359481 (6:143488314 T>C), RS1000480292 (6:143461065 G>C), RS1000575058 (6:143452373 A>G), RS1000624206 (6:143451896 A>G), RS1000627885 (6:143483985 A>G), RS1000747563 (6:143457568 T>C), RS1000771879 (6:143460114 C>A,T), RS1000877297 (6:143466577 A>C,G), RS1000980276 (6:143482962 CAAGCTTTTTAT>C), RS1000989947 (6:143466135 G>C)

Disease associations

OMIM: gene MIM:603164 | disease phenotypes: MIM:614882, MIM:617370, MIM:214100

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 10A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Strong	Autosomal recessive
peroxisome biogenesis disorder 10B	Strong	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 (5): peroxisome biogenesis disorder 10A (Zellweger) (MONDO:0013948), peroxisome biogenesis disorder 10B (MONDO:0054549), peroxisome biogenesis disorder (MONDO:0019234), peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953), Zellweger spectrum disorders (MONDO:0019609)

Orphanet (2): Zellweger syndrome (Orphanet:912), Peroxisome biogenesis disorder (Orphanet:79189)

HPO phenotypes

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

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000121	Nephrocalcinosis
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009251_1	Skin aging measurement	5.000000e-09

MeSH disease descriptors (3)

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
C536664	Peroxisome biogenesis disorders (supp.)
C531857	Zellweger leukodystrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067260 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.99	Kd	10.22	nM	CHEMBL3752910
7.94	ED50	11.46	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149907: Binding affinity to human PEX3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0102	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Arsenic Trioxide	increases expression, affects cotreatment, decreases expression	2
Tretinoin	affects cotreatment, decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Chenodeoxycholic Acid	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Selenium	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Vitamin E	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652949	Binding	Binding affinity to human PEX3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5KM	HAP1 PEX3 (-) 2	Cancer cell line	Male
CVCL_B5KN	HAP1 PEX3 (-) 3	Cancer cell line	Male
CVCL_E0JX	Ubigene HeLa PEX3 KO	Cancer cell line	Female
CVCL_XR53	HAP1 PEX3 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
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
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