PEX2

Summary

PEX2 (peroxisomal biogenesis factor 2, HGNC:9717) is a protein-coding gene on chromosome 8q21.13, encoding Peroxisome biogenesis factor 2 (P28328). E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.

This gene encodes an integral peroxisomal membrane protein required for peroxisome biogenesis. The protein is thought to be involved in peroxisomal matrix protein import. Mutations in this gene result in one form of Zellweger syndrome and infantile Refsum disease. Alternative splicing results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 5828 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 540 total — 35 pathogenic, 36 likely-pathogenic
• Phenotypes (HPO): 165
• Druggable target: yes
• MANE Select transcript: NM_000318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9717
Approved symbol	PEX2
Name	peroxisomal biogenesis factor 2
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	PMP35, PAF-1, RNF72, ZWS3
Ensembl gene	ENSG00000164751
Ensembl biotype	protein_coding
OMIM	170993
Entrez	5828

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 25 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000357039, ENST00000518986, ENST00000519956, ENST00000520103, ENST00000520203, ENST00000522527, ENST00000898979, ENST00000898980, ENST00000898981, ENST00000898982, ENST00000898983, ENST00000898984, ENST00000898985, ENST00000898986, ENST00000898987, ENST00000898988, ENST00000898989, ENST00000898990, ENST00000898991, ENST00000933667, ENST00000933668, ENST00000948869, ENST00000948870, ENST00000948871, ENST00000948872, ENST00000948873

RefSeq mRNA: 4 — MANE Select: NM_000318 NM_000318, NM_001079867, NM_001172086, NM_001172087

CCDS: CCDS6221

Canonical transcript exons

ENST00000357039 — 4 exons

Exon	Start	End
ENSE00001357600	76986187	76986296
ENSE00002099329	76988307	76988338
ENSE00002101026	76999990	77000078
ENSE00002122093	76980258	76984195

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 95.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7914 / max 775.5929, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93648	24.3582	1797
93649	1.8612	1118
93647	0.5720	323

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	95.05	gold quality
ventricular zone	UBERON:0003053	94.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.41	gold quality
islet of Langerhans	UBERON:0000006	94.32	gold quality
rectum	UBERON:0001052	94.02	gold quality
monocyte	CL:0000576	93.76	gold quality
adrenal tissue	UBERON:0018303	93.61	gold quality
leukocyte	CL:0000738	93.56	gold quality
mononuclear cell	CL:0000842	93.55	gold quality
colonic epithelium	UBERON:0000397	93.33	gold quality
right adrenal gland cortex	UBERON:0035827	93.18	gold quality
gall bladder	UBERON:0002110	93.11	gold quality
body of pancreas	UBERON:0001150	93.08	gold quality
right adrenal gland	UBERON:0001233	92.81	gold quality
left adrenal gland	UBERON:0001234	92.57	gold quality
pancreas	UBERON:0001264	92.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.49	gold quality
secondary oocyte	CL:0000655	92.42	gold quality
muscle of leg	UBERON:0001383	92.26	gold quality
left adrenal gland cortex	UBERON:0035825	92.20	gold quality
gastrocnemius	UBERON:0001388	92.14	gold quality
calcaneal tendon	UBERON:0003701	92.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.10	gold quality
minor salivary gland	UBERON:0001830	92.09	gold quality
right uterine tube	UBERON:0001302	92.07	gold quality
granulocyte	CL:0000094	92.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.97	gold quality
endocervix	UBERON:0000458	91.81	gold quality
adrenal gland	UBERON:0002369	91.79	gold quality
body of uterus	UBERON:0009853	91.77	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MYC	Repression

Upstream regulators (CollecTRI, top): ATF1

miRNA regulators (miRDB)

105 targeting PEX2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806

Literature-anchored findings (GeneRIF, showing 6)

• The cause of the syndrome in this patient was a point mutation that resulted in the premature termination of peroxisome assembly factor-1. (PMID:1546315)
• Genetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA (PMID:21392394)
• Ischemic wound healing is retarded in mice subjected to recombinant PEX2 injections or viral transduction with PEX2-lentivurus. (PMID:21903356)
• the carrier frequencies for two PEX2 mutations causative of the severe Zellweger syndrome spectrum phenotype in Ashkenazi Jews (PMID:23590336)
• PEX2 is required for peroxisome autophagy during starvation. (PMID:27597759)
• we report here that PEX2 and other peroxins are essential for the viability of liver cancer cells (PMID:29458144)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex2	ENSDARG00000062421
mus_musculus	Pex2	ENSMUSG00000040374
rattus_norvegicus	Pex2	ENSRNOG00000008748
drosophila_melanogaster	Pex2	FBGN0035876
caenorhabditis_elegans		WBGENE00004192

Protein

Protein identifiers

Peroxisome biogenesis factor 2 — P28328 (reviewed: P28328)

Alternative names: 35 kDa peroxisomal membrane protein, Peroxin-2, Peroxisomal membrane protein 3, Peroxisome assembly factor 1, RING finger protein 72

All UniProt accessions (2): E5RIW9, P28328

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling. The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane. PEX2 also regulates peroxisome organization by acting as a E3 ubiquitin-protein ligase. PEX2 ubiquitinates PEX5 during its passage through the retrotranslocation channel: catalyzes monoubiquitination of PEX5 at ‘Cys-11’, a modification that acts as a signal for PEX5 extraction into the cytosol. Required for pexophagy in response to starvation by mediating ubiquitination of peroxisomal proteins, such as PEX5 and ABCD3/PMP70. Also involved in the response to reactive oxygen species (ROS) by mediating ‘Lys-48’-linked polyubiquitination and subsequent degradation of PNPLA2/ATGL, thereby regulating lipolysis.

Subunit / interactions. Component of the PEX2-PEX10-PEX12 retrotranslocation channel, composed of PEX2, PEX10 and PEX12.

Subcellular location. Peroxisome membrane.

Post-translational modifications. Forms intramolecular and intermolecular disulfide bonds in response to reactive oxygen species (ROS), promoting higher stability.

Disease relevance. Peroxisome biogenesis disorder complementation group 5 (PBD-CG5) [MIM:614866] 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 5A (PBD5A) [MIM:614866] 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 5B (PBD5B) [MIM:614867] A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the pex2/pex10/pex12 family.

RefSeq proteins (4): NP_000309, NP_001073336, NP_001165557, NP_001165558 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR006845	Pex_N	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR025654	PEX2/10	Family
IPR045859	RING-HC_PEX2	Domain

Pfam: PF04757

UniProt features (28 total): binding site 8, topological domain 6, sequence variant 6, transmembrane region 5, chain 1, zinc finger region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28328-F1	81.17	0.40

Functional residue map

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

Ligand- & substrate-binding residues (8): 244; 247; 259; 261; 264; 267; 280; 283

Post-translational modifications (1): 84

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: 537 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_MACROAUTOPHAGY, PATIL_LIVER_CANCER, GOBP_PROTEIN_DESTABILIZATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_PROTEIN_MONOUBIQUITINATION

GO Biological Process (16): very long-chain fatty acid metabolic process (GO:0000038), pexophagy (GO:0000425), protein monoubiquitination (GO:0006513), fatty acid beta-oxidation (GO:0006635), peroxisome organization (GO:0007031), protein import into peroxisome matrix (GO:0016558), protein import into peroxisome matrix, receptor recycling (GO:0016562), protein destabilization (GO:0031648), cellular response to reactive oxygen species (GO:0034614), protein import into peroxisome matrix, substrate release (GO:0044721), negative regulation of fibroblast proliferation (GO:0048147), negative regulation of epithelial cell proliferation (GO:0050680), response to amino acid starvation (GO:1990928), protein transport (GO:0015031), protein ubiquitination (GO:0016567), protein unfolding (GO:0043335)

GO Molecular Function (6): zinc ion binding (GO:0008270), transmembrane protein transporter activity (GO:0008320), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleoplasm (GO:0005654), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), Cdc73/Paf1 complex (GO:0016593), peroxisome (GO:0005777)

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
cellular anatomical structure	3
protein import into peroxisome matrix	2
negative regulation of cell population proliferation	2
fatty acid metabolic process	1
macroautophagy	1
autophagy of peroxisome	1
protein ubiquitination	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
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
receptor recycling	1
regulation of protein stability	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
protein-containing complex disassembly	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
response to starvation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein modification by small protein conjugation	1
cellular process	1
transition metal ion binding	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

963 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX2	PEX10	O60683	999
PEX2	PEX12	O00623	999
PEX2	PEX13	Q92968	984
PEX2	PEX5	P50542	969
PEX2	PEX6	Q13608	962
PEX2	PEX3	P56589	955
PEX2	PEX19	P40855	954
PEX2	PEX7	O00628	953
PEX2	PEX14	O75381	951
PEX2	PEX16	Q9Y5Y5	928
PEX2	PEX11B	O96011	924
PEX2	PEX26	Q7Z412	920
PEX2	PEX1	O43933	894
PEX2	PEX5L	Q8IYB4	856
PEX2	ABCD3	P28288	847

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PEX2	PEX19	psi-mi:“MI:0407”(direct interaction)	0.590
PEX19	PEX2	psi-mi:“MI:0407”(direct interaction)	0.590
UBE2A	RNF40	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
PEX12	PEX2	psi-mi:“MI:0915”(physical association)	0.400
UBE2B	RNF40	psi-mi:“MI:0914”(association)	0.350
	PEX2	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
PEX19	KCNN4	psi-mi:“MI:0914”(association)	0.350
PEX14	PEX12	psi-mi:“MI:0914”(association)	0.350
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
BUD13	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
EFTUD2	NACA	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
ILF3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
RPS11	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
U2AF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
ZNF800	MED19	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
cirA2	PEX2	psi-mi:“MI:0915”(physical association)	0.000
PEX2	ERG28	psi-mi:“MI:0915”(physical association)	0.000
PEX2	TLE1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), C14orf1 (Two-hybrid), TLE1 (Two-hybrid), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX10 (Reconstituted Complex), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS), PEX2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8FG46, A0A1L8FM16, A0A1L8FZ98, A0A1L8H814, A1L3G9, A8X0L4, B0JYZ2, B1AUE5, B9X187, C0HKD7, E7F4V8, E7FE40, F1QB30, F1S5L4, O88177, P24392, P28328, P32800, P55098, P97564, Q00940, Q05568, Q059Y8, Q06438, Q19189, Q19337, Q28EH9, Q3U213, Q3UF64, Q5GJ77, Q5RAG4, Q5SNQ7, Q5Z880, Q61586, Q642F4, Q68F70, Q6DFK1, Q6INN0, Q6NPT7, Q6NZ21

Diamond homologs: A0A1L8FZ98, E7F4V8, P24392, P28328, P55098, Q06438, Q75JQ3, Q9CA86, G2Q1C9, P51021, C4R3D4, Q01964, Q99155

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	PEX2	ubiquitination
PEX2	“up-regulates activity”	ABCD3	ubiquitination
PEX2	“down-regulates quantity by destabilization”	PEX5	ubiquitination
PEX2	“up-regulates activity”	UBE2D2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
E3 ubiquitin ligases ubiquitinate target proteins	6	44.7×	3e-07
mRNA Splicing - Major Pathway	6	12.6×	3e-04
Dengue Virus-Host Interactions	6	10.5×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	5	14.3×	6e-04
RNA splicing	5	13.8×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	36
Uncertain significance	256
Likely benign	142
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071201	NM_000318.3(PEX2):c.115C>T (p.Gln39Ter)	Pathogenic
1206131	NM_000318.3(PEX2):c.286C>T (p.Gln96Ter)	Pathogenic
1323437	NM_000318.3(PEX2):c.668G>A (p.Trp223Ter)	Pathogenic
1357556	NM_000318.3(PEX2):c.416_417del (p.Val139fs)	Pathogenic
13704	NM_000318.3(PEX2):c.355C>T (p.Arg119Ter)	Pathogenic
139589	NM_000318.3(PEX2):c.739T>C (p.Cys247Arg)	Pathogenic
139590	NM_000318.3(PEX2):c.669G>A (p.Trp223Ter)	Pathogenic
1402879	NM_000318.3(PEX2):c.571del (p.Tyr190_Met191insTer)	Pathogenic
1434446	NM_000318.3(PEX2):c.10A>T (p.Arg4Ter)	Pathogenic
1440447	NM_000318.3(PEX2):c.386T>A (p.Leu129Ter)	Pathogenic
1442703	NM_000318.3(PEX2):c.220dup (p.Ala74fs)	Pathogenic
1445756	NM_000318.3(PEX2):c.524del (p.Ser175fs)	Pathogenic
1455464	NM_000318.3(PEX2):c.387_396dup (p.Gly133fs)	Pathogenic
1458316	NM_000318.3(PEX2):c.455_456insG (p.Ile152fs)	Pathogenic
1458503	NM_000318.3(PEX2):c.24_25del (p.Lys9fs)	Pathogenic
1459961	NM_000318.3(PEX2):c.550_551insC (p.Cys184fs)	Pathogenic
1722347	NC_000008.10:g.(?77892493)(77912525_?)del	Pathogenic
1968031	NM_000318.3(PEX2):c.118del (p.Cys40fs)	Pathogenic
2019116	NM_000318.3(PEX2):c.414_426dup (p.Ile143fs)	Pathogenic
2019730	NM_000318.3(PEX2):c.15dup (p.Glu6fs)	Pathogenic
2070891	NM_000318.3(PEX2):c.39_40del (p.Arg13fs)	Pathogenic
2115889	NM_000318.3(PEX2):c.475C>T (p.Gln159Ter)	Pathogenic
2422870	NC_000008.10:g.(?77895497)(77896414_?)del	Pathogenic
2691533	NM_000318.3(PEX2):c.77_79delinsTT (p.Asn26fs)	Pathogenic
2692693	NM_000318.3(PEX2):c.369del (p.Leu123fs)	Pathogenic
2772984	NM_000318.3(PEX2):c.318T>A (p.Tyr106Ter)	Pathogenic
2800172	NM_000318.3(PEX2):c.320_326del (p.Ala107fs)	Pathogenic
2838200	NM_000318.3(PEX2):c.470del (p.Phe157fs)	Pathogenic
2862292	NM_000318.3(PEX2):c.285T>G (p.Tyr95Ter)	Pathogenic
3013832	NM_000318.3(PEX2):c.113del (p.Thr38fs)	Pathogenic

SpliceAI

668 predictions. Top by Δscore:

Variant	Effect	Δscore
8:76986297:C:CC	acceptor_gain	1.0000
8:76988195:AAT:A	donor_gain	1.0000
8:76999986:TGACC:T	donor_loss	1.0000
8:76999987:GAC:G	donor_loss	1.0000
8:77000024:A:C	donor_gain	1.0000
8:76984194:CT:C	acceptor_gain	0.9900
8:76984196:C:CC	acceptor_gain	0.9900
8:76984196:CTAGG:C	acceptor_loss	0.9900
8:76986301:A:C	acceptor_gain	0.9900
8:76986183:TCA:T	donor_loss	0.9800
8:76986184:C:CA	donor_loss	0.9800
8:76986185:A:AG	donor_loss	0.9800
8:76986186:CCTT:C	donor_loss	0.9800
8:76986293:GAAGC:G	acceptor_loss	0.9800
8:76986296:GCTAC:G	acceptor_loss	0.9800
8:76986297:CTA:C	acceptor_loss	0.9800
8:76986298:T:G	acceptor_loss	0.9800
8:76988179:ATAT:A	donor_gain	0.9800
8:76988180:T:C	donor_gain	0.9800
8:77000028:T:A	donor_gain	0.9800
8:76988197:T:TA	donor_gain	0.9700
8:76984192:GTCT:G	acceptor_gain	0.9600
8:76986187:C:T	donor_loss	0.9600
8:76986295:AG:A	acceptor_gain	0.9600
8:76988216:TC:T	donor_gain	0.9600
8:76986293:GAAG:G	acceptor_gain	0.9500
8:76999988:A:AC	donor_gain	0.9500
8:76999989:C:CC	donor_gain	0.9500
8:76983944:A:AC	donor_gain	0.9400
8:76983945:C:CC	donor_gain	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000110204 (8:76987357 C>A), RS1000142981 (8:76987675 A>C), RS1000343972 (8:76980819 T>G), RS1000447819 (8:76981564 A>G), RS1000555701 (8:76992312 C>A), RS1000645246 (8:77002200 G>A), RS1000780993 (8:76981070 C>T), RS1000788711 (8:76998914 T>C), RS1000940423 (8:76993388 A>G), RS1001039736 (8:76992659 T>C), RS1001044289 (8:76999731 C>A), RS1001077224 (8:76999967 G>A), RS1001162005 (8:76984233 T>C,G), RS1001163466 (8:76998654 C>T), RS1001283535 (8:76989782 C>T)

Disease associations

OMIM: gene MIM:170993 | disease phenotypes: MIM:614866, MIM:614867, MIM:214100

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 5B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Definitive	Autosomal recessive
peroxisome biogenesis disorder 5A (Zellweger)	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 (5): peroxisome biogenesis disorder 5A (Zellweger) (MONDO:0013932), Zellweger spectrum disorders (MONDO:0019609), peroxisome biogenesis disorder 5B (MONDO:0013933), peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953), peroxisome biogenesis disorder (MONDO:0019234)

Orphanet (4): Zellweger syndrome (Orphanet:912), Neonatal adrenoleukodystrophy (Orphanet:44), Peroxisome biogenesis disorder (Orphanet:79189), Infantile Refsum disease (Orphanet:772)

HPO phenotypes

165 total (30 of 165 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000107	Renal cyst
HP:0000113	Polycystic kidney dysplasia
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
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:0000311	Round face
HP:0000316	Hypertelorism
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:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000175_13	Height	5.000000e-08
GCST000817_98	Height	7.000000e-13
GCST000880_33	Menarche (age at onset)	3.000000e-09
GCST001099_13	Sudden cardiac arrest	2.000000e-06
GCST002541_66	Menarche (age at onset)	7.000000e-17
GCST002646_15	Infant length	4.000000e-06
GCST002647_74	Height	6.000000e-30
GCST003807_7	Systolic blood pressure response to hydrochlorothiazide in hypertension	7.000000e-06
GCST003993_9	Menarche (age at onset)	3.000000e-08
GCST004294_11	Nicotine dependence	1.000000e-06
GCST008144_3	Fasting plasma glucose	3.000000e-07
GCST008839_278	Height	3.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004278	sudden cardiac arrest
EFO:0006785	infant body height
EFO:0006944	systolic blood pressure change measurement

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): CHEMBL5465285 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
pentanal	increases methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
butyraldehyde	increases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
caprylic aldehyde	increases methylation	1
mercuric bromide	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
heptanal	increases methylation	1
chromium hexavalent ion	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	decreases expression	1
Lead	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	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
CHEMBL5338450	Binding	Binding affinity to Paf1 (unknown origin) at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KF	N/Tert-1 PXMP3	Telomerase immortalized cell line	Male

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