PEX1

Summary

PEX1 (peroxisomal biogenesis factor 1, HGNC:8850) is a protein-coding gene on chromosome 7q21.2, encoding Peroxisomal ATPase PEX1 (O43933). Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling. It is a selective cancer dependency (DepMap: 21.3% of cell lines).

This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5189 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder due to PEX1 defect (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,692 total — 130 pathogenic, 192 likely-pathogenic
• Phenotypes (HPO): 180
• Cancer dependency (DepMap): dependent in 21.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8850
Approved symbol	PEX1
Name	peroxisomal biogenesis factor 1
Location	7q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127980
Ensembl biotype	protein_coding
OMIM	602136
Entrez	5189

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000248633, ENST00000422866, ENST00000428214, ENST00000438045, ENST00000469417, ENST00000476923, ENST00000477342, ENST00000484913, ENST00000496092, ENST00000496420, ENST00000901045, ENST00000914334, ENST00000914335, ENST00000914336, ENST00000914337, ENST00000914338, ENST00000951786, ENST00000951787, ENST00000951788, ENST00000951789, ENST00000951790

RefSeq mRNA: 3 — MANE Select: NM_000466 NM_000466, NM_001282677, NM_001282678

CCDS: CCDS5627, CCDS64710

Canonical transcript exons

ENST00000248633 — 24 exons

Exon	Start	End
ENSE00000877387	92528307	92528520
ENSE00000877389	92518995	92519078
ENSE00003462174	92511580	92511703
ENSE00003495619	92522102	92522245
ENSE00003506214	92506248	92506344
ENSE00003529841	92491272	92491502
ENSE00003530846	92509329	92509411
ENSE00003545122	92518141	92518255
ENSE00003550883	92510944	92511047
ENSE00003562198	92501507	92501673
ENSE00003594027	92494487	92494629
ENSE00003614712	92489714	92489911
ENSE00003620142	92489293	92489423
ENSE00003621590	92513848	92513967
ENSE00003651842	92492953	92493129
ENSE00003659773	92499704	92499838
ENSE00003659894	92504732	92504902
ENSE00003671296	92501890	92502079
ENSE00003671483	92494293	92494396
ENSE00003683482	92503041	92503195
ENSE00003683727	92517276	92518042
ENSE00003687712	92496713	92496777
ENSE00003692281	92506994	92507126
ENSE00003848582	92487025	92487541

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 92.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.5238 / max 1554.9970, expressed in 1756 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84795	11.9500	1750
84793	0.2733	108
84794	0.2432	96
84792	0.0364	5
84790	0.0209	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.92	gold quality
body of pancreas	UBERON:0001150	90.49	gold quality
mucosa of stomach	UBERON:0001199	89.22	gold quality
skin of leg	UBERON:0001511	89.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.00	gold quality
skin of abdomen	UBERON:0001416	88.98	gold quality
cerebellar hemisphere	UBERON:0002245	88.94	gold quality
rectum	UBERON:0001052	88.85	gold quality
cerebellar cortex	UBERON:0002129	88.75	gold quality
metanephros cortex	UBERON:0010533	88.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.48	gold quality
left lobe of thyroid gland	UBERON:0001120	88.39	gold quality
tibial nerve	UBERON:0001323	88.33	gold quality
right lobe of thyroid gland	UBERON:0001119	88.32	gold quality
left ovary	UBERON:0002119	88.17	gold quality
right uterine tube	UBERON:0001302	87.96	gold quality
right ovary	UBERON:0002118	87.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.88	gold quality
thyroid gland	UBERON:0002046	87.53	gold quality
minor salivary gland	UBERON:0001830	87.40	gold quality
adenohypophysis	UBERON:0002196	87.33	gold quality
adrenal tissue	UBERON:0018303	87.25	gold quality
endocervix	UBERON:0000458	87.17	gold quality
body of uterus	UBERON:0009853	86.96	gold quality
transverse colon	UBERON:0001157	86.83	gold quality
pituitary gland	UBERON:0000007	86.80	gold quality
pancreas	UBERON:0001264	86.79	gold quality
right coronary artery	UBERON:0001625	86.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.72	gold quality
zone of skin	UBERON:0000014	86.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting PEX1, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-1238-3P	95.27	62.25	552

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 21.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 27)

• Missense mutations in PEX1 cause the milder forms of the peroxisome biogenesis disorders, whereas insertions, deletions, and nonsense mutations are associated with severe clinical phenotypes. (PMID:12032265)
• We have evaluated the impact of novel mutations, along with that of the two most common PEX1 mutations, in PBD patients by determining the levels of PEX1 mRNA, PEX1 protein, and peroxisome protein import. (PMID:12402331)
• complete lack of PEX1 is associated with Zellweger syndrome (PMID:12840548)
• overview of the currently known PEX1 mutations in Zellweger Syndrome [review] (PMID:16086329)
• analysis of PEX1 coding mutations and 5’ UTR regulatory polymorphisms (PMID:16088892)
• Molecular confirmation of the clinical and biochemical diagnosis will allow the prediction of the clinical course of disease in individual PBD cases. (PMID:16141001)
• Insufficient binding to Pex1p x Pex6p complexes, or mislocalization of patient-derived Pex26p mutants is most likely responsible for the complementation group impaired peroxisome biogenesis. (PMID:16257970)
• Studies provide empirical data to estimate the relative fraction of disease-causing alleles that occur in the coding and splice junction sequences of PEX1 gene. (PMID:19105186)
• A 5’ UTR polymorphism at position c.-53 and a promoter polymorphism 137 bp upstream of the PEX1 start codon are identified but strongly differing survival By genotype-phenotype analysis. (PMID:21846392)
• the variants in PEX genes of a family (PMID:23247051)
• results suggested that peroxisome biogenesis requires Pex1p- and Pex6p-regulated dissociation of Pex14p from Pex26p (PMID:25016021)
• Mutations in PEX1 gene is associated with Heimler Syndrome. (PMID:26387595)
• Our structural data suggest that the tilting of a central segment of a Pex1-Pex6 pair is responsible for polypeptide movement. (PMID:26476099)
• A combination of a known missense and novel frameshift variant in PEX1 identified in a family with Heimler syndrome. (PMID:27302843)
• As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with Heimler syndrome, patients with sensorineural hearing lossand retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes. (PMID:27633571)
• heterozygous mutations in the PEX1 gene in two Chinese newborns with Zellweger syndrome (PMID:28432012)
• Major finding is linking peroxisome biogenesis factor 1 (PEX1) to obesity phenotypes, a novel mechanism of peroxisomal biogenesis and metabolism underlying the development of childhood obesity. (PMID:28508493)
• This study provides evidence suggesting that monoubiquitinated PEX5 interacts directly with both PEX1 and PEX6 through its ubiquitin moiety and that the PEX5 polypeptide chain is globally unfolded during the ATP-dependent extraction event. (PMID:29884772)
• This article reviews the abundant records of missense mutations described in Peroxisome biogenesis disorders patients with the aim to classify and rationalize them by mapping them onto a homology model of the human Pex1/Pex6 complex. [review] (PMID:31374812)
• There are no significant differences between PEX1-, PEX6-, and PEX26-associated phenotypes inclinical and genetic spectrum of Heimler syndrome. (PMID:31831025)
• The peroxisomal disorder spectrum and Heimler syndrome: Deep phenotyping and review of the literature. (PMID:32866347)
• Depletion of HNRNPA1 induces peroxisomal autophagy by regulating PEX1 expression. (PMID:33545634)
• Two siblings with Heimler syndrome caused by PEX1 variants: follow-up of ophthalmologic findings. (PMID:33955814)
• Comparison of human PEX knockout cell lines suggests a dual role of PEX1 in peroxisome biogenesis. (PMID:36534601)
• Ophthalmic Manifestations of Heimler Syndrome in Two Siblings With PEX1 Variants. (PMID:37092661)
• Novel PEX1 mutations in fibroblasts from children with Zellweger spectrum disorders exhibit temperature sensitive characteristics. (PMID:37385119)
• Systematic study of ophthalmological findings in 10 patients with PEX1-mediated Zellweger spectrum disorder. (PMID:38664000)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex1	ENSDARG00000098904
mus_musculus	Pex1	ENSMUSG00000005907
rattus_norvegicus	Pex1	ENSRNOG00000025991
drosophila_melanogaster	Pex1	FBGN0013563
caenorhabditis_elegans		WBGENE00004191

Paralogs (5): PEX6 (ENSG00000124587), NVL (ENSG00000143748), AFG2A (ENSG00000145375), VCP (ENSG00000165280), AFG2B (ENSG00000171763)

Protein

Protein identifiers

Peroxisomal ATPase PEX1 — O43933 (reviewed: O43933)

Alternative names: Peroxin-1, Peroxisome biogenesis disorder protein 1, Peroxisome biogenesis factor 1

All UniProt accessions (3): O43933, A0A0C4DG33, H7BZH3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling. Specifically recognizes PEX5 monoubiquitinated at ‘Cys-11’, and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel. Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5.

Subunit / interactions. Homooligomer; homooligomerizes in the cytosol, interaction with PEX6 promotes dissociation of the homooligomer. Interacts with PEX6; forming the PEX1-PEX6 AAA ATPase complex, which is composed of a heterohexamer formed by a trimer of PEX1-PEX6 dimers. Interacts indirectly with PEX26, via its interaction with PEX6.

Subcellular location. Cytoplasm. Cytosol. Peroxisome membrane.

Disease relevance. Peroxisome biogenesis disorder complementation group 1 (PBD-CG1) [MIM:214100] 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 1A (PBD1A) [MIM:214100] A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD1A is an autosomal recessive systemic disorder characterized clinically 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 1B (PBD1B) [MIM:601539] 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. Heimler syndrome 1 (HMLR1) [MIM:234580] A form of Heimler syndrome, a very mild peroxisome biogenesis disorder characterized by sensorineural hearing loss, amelogenesis imperfecta resulting in enamel hyoplasia of the secondary dentition, nail defects, and occasional or late-onset retinal pigmentation abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the AAA ATPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43933-1	1	yes
O43933-2	2

RefSeq proteins (3): NP_000457, NP_001269606, NP_001269607 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR009010	Asp_de-COase-like_dom_sf	Homologous_superfamily
IPR015342	PEX1-N_C-lobe	Domain
IPR015343	PEX1-N-lobe	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029067	CDC48_domain_2-like_sf	Homologous_superfamily
IPR041569	AAA_lid_3	Domain
IPR050168	AAA_ATPase_domain	Family

Pfam: PF00004, PF09262, PF09263, PF17862

Enzyme classification (BRENDA):

• EC 3.6.4.7 — peroxisome-assembly ATPase (BRENDA: 15 organisms, 53 substrates, 5 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.17–0.7	2

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (36 total): sequence variant 19, mutagenesis site 4, modified residue 4, region of interest 2, sequence conflict 2, binding site 2, chain 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43933-F1	67.19	0.08

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 (2): 599–606; 881–888

Post-translational modifications (4): 354, 1181, 1209, 1211

Mutagenesis-validated functional residues (4):

Position	Phenotype
605	in a1 mutant; abolished atp-binding; decreased interaction with pex6; decreased localization to peroxisomal membranes.
662	in b1 mutant; abolished atp hydrolysis; decreased interaction with pex6; decreased localization to peroxisomal membranes
887	in a2 mutant; abolished atp-binding; decreased interaction with pex6; decreased localization to peroxisomal membranes.
940	in b2 mutant; abolished atp hydrolysis; does not affect interaction with pex6; does not affect localization to peroxisom

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 0 (showing top):

GO Biological Process (7): protein targeting to peroxisome (GO:0006625), peroxisome organization (GO:0007031), protein import into peroxisome matrix (GO:0016558), protein import into peroxisome matrix, receptor recycling (GO:0016562), protein unfolding (GO:0043335), microtubule-based peroxisome localization (GO:0060152), protein transport (GO:0015031)

GO Molecular Function (8): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein-containing complex binding (GO:0044877), ubiquitin-modified protein reader activity (GO:0140036), protein transporter activity (GO:0140318), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): cytoplasm (GO:0005737), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
establishment of protein localization to peroxisome	2
binding	2
protein targeting	1
organelle organization	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
protein localization to peroxisome	1
receptor recycling	1
protein import into peroxisome matrix	1
cellular process	1
microtubule-based process	1
peroxisome localization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
ubiquitin-like protein reader activity	1
transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular anatomical structure	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

2110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX1	PEX5	P50542	915
PEX1	PEX26	Q7Z412	903
PEX1	PEX10	O60683	895
PEX1	PEX2	P28328	894
PEX1	PEX5L	Q8IYB4	882
PEX1	PEX7	O00628	877
PEX1	PEX12	O00623	876
PEX1	PEX13	Q92968	872
PEX1	PEX19	P40855	868
PEX1	PEX16	Q9Y5Y5	852
PEX1	PEX3	P56589	843
PEX1	PEX14	O75381	789
PEX1	TRIM37	O94972	708
PEX1	ABCD3	P28288	698
PEX1	AGPS	O00116	684

IntAct

193 interactions, top by confidence:

A	B	Type	Score
PRKAB1	PRKAB2	psi-mi:“MI:0914”(association)	0.740
ANXA8	PEX1	psi-mi:“MI:0915”(physical association)	0.560
MNDA	PEX1	psi-mi:“MI:0915”(physical association)	0.560
MSH5	PEX1	psi-mi:“MI:0915”(physical association)	0.560
TNNI3	PEX1	psi-mi:“MI:0915”(physical association)	0.560
VDAC2	PEX1	psi-mi:“MI:0915”(physical association)	0.560
ZNF180	PEX1	psi-mi:“MI:0915”(physical association)	0.560
H3C1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
COPS3	PEX1	psi-mi:“MI:0915”(physical association)	0.560
PIAS1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
	PEX1	psi-mi:“MI:0915”(physical association)	0.560
EIF5B	PEX1	psi-mi:“MI:0915”(physical association)	0.560
BATF	PEX1	psi-mi:“MI:0915”(physical association)	0.560
SERINC3	PEX1	psi-mi:“MI:0915”(physical association)	0.560
WWP2	PEX1	psi-mi:“MI:0915”(physical association)	0.560
GALNT6	PEX1	psi-mi:“MI:0915”(physical association)	0.560
RYBP	PEX1	psi-mi:“MI:0915”(physical association)	0.560
TBC1D22A	PEX1	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP3	PEX1	psi-mi:“MI:0915”(physical association)	0.560
MYL11	PEX1	psi-mi:“MI:0915”(physical association)	0.560
STOML2	PEX1	psi-mi:“MI:0915”(physical association)	0.560
DCAF8	PEX1	psi-mi:“MI:0915”(physical association)	0.560
ING4	PEX1	psi-mi:“MI:0915”(physical association)	0.560
KLF3	PEX1	psi-mi:“MI:0915”(physical association)	0.560
ANAPC11	PEX1	psi-mi:“MI:0915”(physical association)	0.560
MBIP	PEX1	psi-mi:“MI:0915”(physical association)	0.560
EPS8L1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
SEMA4C	PEX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (110): PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMU5, A0JPF9, A1A4L5, A4IF69, G3GXG9, O43933, O70362, P19686, P57075, P80108, P80109, Q02108, Q0V9N0, Q14703, Q28CZ7, Q2TBM9, Q3B7N1, Q3U213, Q3U3W5, Q3UY23, Q4ZHS0, Q5BL07, Q5XFW6, Q5ZI67, Q5ZKL5, Q6NRS1, Q6P2P2, Q6ZPR6, Q80Y20, Q86WJ1, Q8BGG7, Q8BWR4, Q8BZW8, Q8C042, Q8L735, Q8LEV3, Q8NBF2, Q8R2H5, Q8TF42, Q8VZ10

Diamond homologs: A0A061IR73, A0A7N9VSG0, A4G0S4, A6UQT3, A6VHR1, A7YSY2, A9A916, C4QXI8, C4R6C2, D1CDT8, D4A2B7, G1X4S3, G1X7C7, G3GXG9, O05209, O13764, O14325, O15381, O18413, O26824, O28303, O28972, O43933, O60058, O74941, P03974, P23787, P24004, P25694, P32794, P33289, P33760, P34124, P36966, P41836, P46462, P46463, P46468, P54609, P54774

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PEX1	up-regulates	Protein_localization_to_peroxisome
PEX6	“up-regulates activity”	PEX1	binding
PEX1	“up-regulates activity”	PEX5	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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	6	13.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1692 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	130
Likely pathogenic	192
Uncertain significance	506
Likely benign	641
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068549	NM_000466.3(PEX1):c.1456G>T (p.Glu486Ter)	Pathogenic
1070094	NM_000466.3(PEX1):c.2550dup (p.Ile851fs)	Pathogenic
1070573	NM_000466.3(PEX1):c.3450T>A (p.Cys1150Ter)	Pathogenic
1070990	NM_000466.3(PEX1):c.2738_2741dup (p.Tyr914Ter)	Pathogenic
1074109	NC_000007.13:g.(?92148299)(92157759_?)del	Pathogenic
1076872	NM_000466.3(PEX1):c.3301G>T (p.Glu1101Ter)	Pathogenic
1098755	NM_000466.3(PEX1):c.788_789del (p.Thr263fs)	Pathogenic
1252071	NM_000466.3(PEX1):c.1240_1359del (p.Ile414_Leu453del)	Pathogenic
1323432	NM_000466.3(PEX1):c.2083_2084del (p.Met695fs)	Pathogenic
1380467	NM_000466.3(PEX1):c.2516G>A (p.Trp839Ter)	Pathogenic
1384557	NM_000466.3(PEX1):c.3259_3260del (p.Phe1086_Leu1087insTer)	Pathogenic
1395451	NC_000007.14:g.92528411_92528711del	Pathogenic
1404596	NM_000466.3(PEX1):c.2164del (p.Val723fs)	Pathogenic
1404606	NM_000466.3(PEX1):c.2162T>A (p.Leu721Ter)	Pathogenic
1422035	NM_000466.3(PEX1):c.1795G>T (p.Gly599Ter)	Pathogenic
1423136	NM_000466.3(PEX1):c.1916dup (p.Asn639fs)	Pathogenic
1428826	NM_000466.3(PEX1):c.3005_3011dup (p.Tyr1004Ter)	Pathogenic
1437796	NM_000466.3(PEX1):c.1963C>T (p.Gln655Ter)	Pathogenic
1446920	NM_000466.3(PEX1):c.786_787del (p.Glu262fs)	Pathogenic
1449026	NM_000466.3(PEX1):c.1955del (p.Val652fs)	Pathogenic
1451905	NM_000466.3(PEX1):c.2464_2477dup (p.Leu826fs)	Pathogenic
1453986	NM_000466.3(PEX1):c.1672G>T (p.Gly558Ter)	Pathogenic
1455008	NC_000007.13:g.(?92135552)(92140371_?)del	Pathogenic
1457173	NM_000466.3(PEX1):c.1208del (p.Asn403fs)	Pathogenic
1457762	NM_000466.3(PEX1):c.607G>T (p.Gly203Ter)	Pathogenic
1457806	NM_000466.3(PEX1):c.34G>T (p.Gly12Ter)	Pathogenic
1459985	NC_000007.13:g.(?92135668)(92140738_?)del	Pathogenic
188851	NM_000466.3(PEX1):c.2391_2392del (p.Arg798fs)	Pathogenic
188897	NM_000466.3(PEX1):c.643_647del (p.Thr215fs)	Pathogenic
188910	NM_000466.3(PEX1):c.782_783del (p.Gln261fs)	Pathogenic

SpliceAI

3296 predictions. Top by Δscore:

Variant	Effect	Δscore
7:92487537:CATAT:C	acceptor_gain	1.0000
7:92487539:TAT:T	acceptor_gain	1.0000
7:92487541:TCTGA:T	acceptor_loss	1.0000
7:92487542:C:CC	acceptor_gain	1.0000
7:92487542:CT:C	acceptor_loss	1.0000
7:92487543:T:A	acceptor_loss	1.0000
7:92489287:ACTT:A	donor_loss	1.0000
7:92489289:TTA:T	donor_loss	1.0000
7:92489290:TA:T	donor_loss	1.0000
7:92489291:A:AC	donor_gain	1.0000
7:92489291:A:AG	donor_loss	1.0000
7:92489291:ACAG:A	donor_gain	1.0000
7:92489292:C:CT	donor_gain	1.0000
7:92489292:CA:C	donor_gain	1.0000
7:92489292:CAG:C	donor_gain	1.0000
7:92489292:CAGC:C	donor_gain	1.0000
7:92489292:CAGCT:C	donor_gain	1.0000
7:92489421:CTC:C	acceptor_gain	1.0000
7:92489423:CC:C	acceptor_loss	1.0000
7:92489423:CCT:C	acceptor_gain	1.0000
7:92489424:C:CA	acceptor_loss	1.0000
7:92489425:T:C	acceptor_gain	1.0000
7:92489429:G:GC	acceptor_gain	1.0000
7:92491287:T:TA	donor_gain	1.0000
7:92491293:T:A	donor_gain	1.0000
7:92491317:T:TA	donor_gain	1.0000
7:92492937:T:TA	donor_gain	1.0000
7:92492947:A:C	donor_gain	1.0000
7:92493125:GACAC:G	acceptor_gain	1.0000
7:92493126:ACAC:A	acceptor_gain	1.0000

AlphaMissense

8397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:92494371:A:C	S984R	0.998
7:92494371:A:T	S984R	0.998
7:92494373:T:G	S984R	0.998
7:92494381:G:T	A981D	0.998
7:92494537:C:G	R959P	0.998
7:92494576:G:T	A946D	0.998
7:92496742:A:C	S918R	0.998
7:92496742:A:T	S918R	0.998
7:92496744:T:G	S918R	0.998
7:92493020:A:G	L1047P	0.997
7:92494339:C:G	R995T	0.997
7:92494345:A:G	L993P	0.997
7:92494348:G:T	A992D	0.997
7:92494519:A:G	L965P	0.997
7:92494541:C:G	D958H	0.997
7:92499762:T:A	K887I	0.997
7:92499780:C:T	G881D	0.997
7:92494354:T:C	D990G	0.996
7:92494369:C:G	R985P	0.996
7:92494378:G:T	A982D	0.996
7:92494379:C:G	A982P	0.996
7:92494531:A:T	V961D	0.996
7:92494540:T:A	D958V	0.996
7:92496731:A:T	V922D	0.996
7:92496777:C:G	G907R	0.996
7:92496777:C:T	G907R	0.996
7:92499781:C:G	G881R	0.996
7:92494330:C:G	R998P	0.995
7:92494339:C:A	R995M	0.995
7:92494345:A:C	L993R	0.995

dbSNP variants (sampled 300 via entrez): RS1000009569 (7:92497692 T>G), RS1000089627 (7:92512635 G>A,T), RS1000423880 (7:92501871 T>A), RS1000538687 (7:92516108 A>T), RS1000662911 (7:92522575 C>T), RS1000791010 (7:92529341 T>G), RS1000810020 (7:92515604 T>C), RS1000825007 (7:92520198 T>G), RS1000885834 (7:92529557 C>A,G), RS1001002071 (7:92512794 T>A), RS1001006189 (7:92487727 C>T), RS1001185762 (7:92513005 A>G), RS1001240192 (7:92527023 G>C,T), RS1001245402 (7:92493313 A>G,T), RS1001247636 (7:92513454 T>C)

Disease associations

OMIM: gene MIM:602136 | disease phenotypes: MIM:214100, MIM:601539, MIM:234580, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 1A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder due to PEX1 defect	Definitive	Autosomal recessive
Heimler syndrome 1	Strong	Autosomal recessive
peroxisome biogenesis disorder 1B	Strong	Autosomal recessive
peroxisome biogenesis disorder	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 due to PEX1 defect	Definitive	AR

Mondo (11): peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953), peroxisome biogenesis disorder 1B (MONDO:0011101), Zellweger spectrum disorders (MONDO:0019609), optic atrophy (MONDO:0003608), peroxisome biogenesis disorder (MONDO:0019234), peroxisome biogenesis disorder due to PEX1 defect (MONDO:0100259), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998), peroxisomal disease (MONDO:0019053), polymicrogyria (MONDO:0000087), (MONDO:0024544)

Orphanet (9): Deafness-enamel hypoplasia-nail defects syndrome (Orphanet:3220), Neonatal adrenoleukodystrophy (Orphanet:44), Zellweger syndrome (Orphanet:912), Peroxisome biogenesis disorder (Orphanet:79189), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Peroxisomal disease (Orphanet:68373), Polymicrogyria (Orphanet:35981), Infantile Refsum disease (Orphanet:772)

HPO phenotypes

180 total (30 of 180 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:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000157	Abnormality of the tongue
HP:0000158	Macroglossia
HP:0000164	Abnormality of the dentition
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000244	Brachyturricephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000272	Malar flattening
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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000175_12	Height	1.000000e-08
GCST90020028_172	Hip circumference adjusted for BMI	5.000000e-18
GCST90020028_465	Hip circumference adjusted for BMI	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D065706	Polymicrogyria	C10.500.507.500.500; C16.131.666.507.500.500
D058499	Retinal Dystrophies	C11.768.585.658
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: no

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
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Hydrogen Peroxide	affects expression	1
Lithium	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Selenium	decreases expression	1
Silicon Dioxide	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Vitamin E	decreases expression	1
Zinc	increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4F73	GM16513	Finite cell line	Male
CVCL_VQ72	PBD009	Finite cell line

Clinical trials (associated diseases)

86 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
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01043640	PHASE2	COMPLETED	Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
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
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy