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): 1,686 total — 120 pathogenic, 189 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 44 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 204
• Cancer dependency (DepMap): dependent in 21.3% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.75 (unconstrained)
• 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: 30 — 16 protein_coding, 8 nonsense_mediated_decay, 6 retained_intron

MANE Select: ENST00000248633

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 5, TSL 3: 1, TSL 5: 2

ENST00000248633, ENST00000422866, ENST00000428214, ENST00000438045, ENST00000469417, ENST00000476923, ENST00000477342, ENST00000484913, ENST00000496092, ENST00000496420, ENST00000901045, ENST00000914334, ENST00000914335, ENST00000914336, ENST00000914337, ENST00000914338, ENST00000951786, ENST00000951787, ENST00000951788, ENST00000951789, ENST00000951790, ENST00000978117, ENST00001011808, ENST00001011810, ENST00001083818, ENST00001106292, ENST00001106293, ENST00001115688, ENST00001118546, ENST00001143239

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.

Highest expression (Bgee): calcaneal tendon, body of pancreas, mucosa of stomach, skin of leg, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PEX1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 48 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	3.1e-106	+1.15	7:92506806:TCCC:T
Skin Not Sun Exposed Suprapubic	eqtl	5.1e-91	+1.20	7:92506806:TCCC:T
Adipose Subcutaneous	eqtl	3.7e-70	+1.23	7:92537789:A:G
Esophagus Mucosa	eqtl	7.6e-68	+1.02	7:92506806:TCCC:T
Thyroid	eqtl	8.1e-66	+1.22	7:92506806:TCCC:T
Breast Mammary Tissue	eqtl	1.7e-58	+1.12	7:92506806:TCCC:T
Nerve Tibial	eqtl	8.2e-54	+0.96	7:92513403:A:T
Adipose Visceral Omentum	eqtl	1.2e-46	+1.09	7:92506806:TCCC:T
Lung	eqtl	3.6e-43	+0.88	7:92506806:TCCC:T
Pancreas	eqtl	1.6e-39	+1.28	7:92506806:TCCC:T
Esophagus Muscularis	eqtl	3.6e-39	+0.93	7:92506806:TCCC:T
Stomach	eqtl	1.5e-37	+1.13	7:92506806:TCCC:T
Colon Transverse	eqtl	5.7e-36	+0.92	7:92506806:TCCC:T
Artery Tibial	eqtl	2.6e-33	+0.74	7:92506806:TCCC:T
Colon Sigmoid	eqtl	1.3e-32	+0.89	7:92506806:TCCC:T
Artery Aorta	eqtl	2.4e-31	+0.94	7:92506806:TCCC:T
Esophagus Gastroesophageal Junction	eqtl	6.9e-31	+1.11	7:92506806:TCCC:T
Spleen	eqtl	2.3e-29	+1.30	7:92506806:TCCC:T
Pituitary	eqtl	2.5e-26	+1.03	7:92506806:TCCC:T
Cells Cultured fibroblasts	eqtl	8.3e-21	+0.85	7:92506806:TCCC:T

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

showing 100 of 294 tissues 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
muscle layer of sigmoid colon	UBERON:0035805	86.68	gold quality
ectocervix	UBERON:0012249	86.56	gold quality
right lobe of liver	UBERON:0001114	86.53	gold quality
body of stomach	UBERON:0001161	86.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.42	gold quality
descending thoracic aorta	UBERON:0002345	86.39	gold quality
right adrenal gland cortex	UBERON:0035827	86.34	gold quality
gastrocnemius	UBERON:0001388	86.22	gold quality
muscle of leg	UBERON:0001383	86.16	gold quality
right adrenal gland	UBERON:0001233	86.12	gold quality
left adrenal gland cortex	UBERON:0035825	86.01	gold quality
cerebellum	UBERON:0002037	85.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.84	gold quality
left adrenal gland	UBERON:0001234	85.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.78	gold quality
lower esophagus	UBERON:0013473	85.77	gold quality
tibial artery	UBERON:0007610	85.75	gold quality
popliteal artery	UBERON:0002250	85.73	gold quality
granulocyte	CL:0000094	85.68	gold quality
small intestine	UBERON:0002108	85.59	gold quality
ovary	UBERON:0000992	85.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.42	gold quality
aorta	UBERON:0000947	85.37	gold quality
spinal cord	UBERON:0002240	85.36	gold quality
left coronary artery	UBERON:0001626	85.33	gold quality
mouth mucosa	UBERON:0003729	85.33	gold quality
right frontal lobe	UBERON:0002810	85.29	gold quality
mucosa of transverse colon	UBERON:0004991	85.25	gold quality
esophagus	UBERON:0001043	85.24	gold quality
vagina	UBERON:0000996	85.22	gold quality
thoracic aorta	UBERON:0001515	85.16	gold quality
ascending aorta	UBERON:0001496	85.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.06	gold quality
lower esophagus mucosa	UBERON:0035834	85.04	gold quality
tendon	UBERON:0000043	85.01	gold quality
right atrium auricular region	UBERON:0006631	85.00	gold quality
sigmoid colon	UBERON:0001159	84.90	gold quality
right lung	UBERON:0002167	84.88	gold quality
spleen	UBERON:0002106	84.84	gold quality
esophagus mucosa	UBERON:0002469	84.84	gold quality
saliva-secreting gland	UBERON:0001044	84.74	gold quality
apex of heart	UBERON:0002098	84.74	gold quality
intestine	UBERON:0000160	84.72	gold quality
cortical plate	UBERON:0005343	84.61	gold quality
adrenal gland	UBERON:0002369	84.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.58	gold quality
stomach	UBERON:0000945	84.55	gold quality
colon	UBERON:0001155	84.52	gold quality
left uterine tube	UBERON:0001303	84.37	gold quality
adrenal cortex	UBERON:0001235	84.33	gold quality
large intestine	UBERON:0000059	84.31	gold quality
coronary artery	UBERON:0001621	84.07	gold quality
upper lobe of left lung	UBERON:0008952	83.93	gold quality
germinal epithelium of ovary	UBERON:0001304	83.75	gold quality
heart left ventricle	UBERON:0002084	83.55	gold quality
ventricular zone	UBERON:0003053	83.54	gold quality
upper lobe of lung	UBERON:0008948	83.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.26	gold quality
monocyte	CL:0000576	83.20	gold quality
omental fat pad	UBERON:0010414	83.20	gold quality
corpus callosum	UBERON:0002336	83.14	gold quality
peritoneum	UBERON:0002358	83.14	gold quality
nucleus accumbens	UBERON:0001882	83.13	gold quality
cardiac atrium	UBERON:0002081	83.08	gold quality
secondary oocyte	CL:0000655	83.04	gold quality
adipose tissue	UBERON:0001013	82.98	gold quality
caudate nucleus	UBERON:0001873	82.98	gold quality
mononuclear cell	CL:0000842	82.91	gold quality
cardiac ventricle	UBERON:0002082	82.87	gold quality
ganglionic eminence	UBERON:0004023	82.85	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	15.6	not detected
Kidney	tissue	13.3	medium
Retina	tissue	12.2
Liver	tissue	12.2	not detected
Thalamus	tissue	11.9
Nucleus accumbens	tissue	11.4
Midbrain	tissue	11.3
Pons	tissue	11.2
Postcentral gyrus	tissue	11.1
Parathyroid gland	tissue	11.0	medium
Superior colliculi	tissue	10.8
Cerebral cortex	tissue	10.7	not detected
Motor cortex	tissue	10.7
Putamen	tissue	10.7
Epididymis	tissue	10.6	medium
Septum	tissue	10.6
Corpus callosum	tissue	10.4
Basal ganglia	tissue	10.3	not detected
Choroid plexus	tissue	10.3
Hippocampal formation	tissue	10.3
Occipital cortex	tissue	10.3
Ventral forebrain	tissue	10.1
Temporal cortex	tissue	10.0
Hypothalamus	tissue	9.9
Entorhinal cortex	tissue	9.9
Prefrontal cortex	tissue	9.8
Retrosplenial and cingulate cortex	tissue	9.8
Retrosplenial cortex	tissue	9.8
Amygdala	tissue	9.7
Somatosensory cortex	tissue	9.7
Insular cortex	tissue	9.7
Substantia nigra	tissue	9.6
Spinal cord	tissue	9.6
Medulla oblongata	tissue	9.3
Tongue	tissue	9.2
Locus coeruleus	tissue	9.2
Periaqueductal gray	tissue	9.2
Rectum	tissue	8.9	medium
Olfactory bulb	tissue	8.8
Salivary gland	tissue	8.6	low
Skeletal muscle	tissue	8.6	medium
Hippocampus	tissue	8.6	not detected
Heart muscle	tissue	8.3	low
Pancreas	tissue	8.3	low
Breast	tissue	8.1	medium
Thyroid gland	tissue	8.1	low
Colon	tissue	8.0	medium
Stomach 1	tissue	7.7	medium
Small intestine	tissue	7.6	medium
Skin 1	tissue	7.5	not detected
Thymus	tissue	7.4
Prostate	tissue	7.3	medium
Frontal cortex	tissue	7.1
Pituitary gland	tissue	6.8
Seminal vesicle	tissue	6.6	not detected
Lymph node	tissue	6.5	not detected
Adrenal gland	tissue	6.5	not detected
Testis	tissue	6.3	not detected
Endometrium 1	tissue	6.3	low
Tonsil	tissue	6.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (17.5), Temporal white matter (17.2), Corpus callosum, genu (white matter) (17.0), Occipital cortex (white matter) (16.6), Cerebellar white matter (15.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PEX1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

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

gnomAD constraint: pLI 3.64e-11, LOEUF 0.746, missense Z 1.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000248633 — one region, missense o/e 0.89. DepMap (CRISPR cell-line fitness): dependent in 21.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SNU-482 (-1.434), 950-5-BIK (-1.375), OVMANA (-1.359), MAPAC-HS-77 (-1.352), RERF-LC-Ad2 (-1.34), SKG-IIIa (-1.257), UOK101 (-1.255), MEL-JUSO (-1.222), PA-TU-8902 (-1.205), HuCCT1 (-1.187), HUP-T3 (-1.173), KCI-MOH1 (-1.14), HT-1197 (-1.131), NUGC-3 (-1.111), TE-1 (-1.094).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1918632) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 44 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver morphology	2
cholestasis	2
postnatal growth retardation	2
bile duct proliferation	2
abnormal bile salt homeostasis	2
hydronephrosis	1
enlarged liver	1
weakness	1
decreased body weight	1
decreased body size	1
hyperglycemia	1
hepatic necrosis	1
liver inflammation	1
premature death	1
dilated heart left ventricle	1
increased liver adenoma incidence	1
liver fibrosis	1
abnormal rod electrophysiology	1
abnormal cone electrophysiology	1
abnormal phospholipid level	1
decreased cardiac muscle contractility	1
abnormal fatty acids level	1
increased fatty acids level	1
decreased fatty acids level	1
increased saturated fatty acids level	1

+19 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3ZBT1	99.9%	Diamond
Pongo abelii	Q5R410	99.9%	Diamond
Komagataella phaffii GS115	C4QXI8	99.8%	Diamond
Sus scrofa	P03974	99.8%	Diamond
Komagataella pastoris	P33289	99.8%	Diamond
Cricetulus griseus	P18708	98.9%	Diamond
Xenopus laevis	P23787	98.4%	Diamond
Xenopus tropicalis	Q6GL04	98.4%	Diamond
Arabidopsis thaliana	Q9LZF6	96.3%	Diamond
Glycine max	P54774	91.6%	Diamond
Capsicum annuum	Q96372	90.0%	Diamond
Aspergillus nidulans FGSC A4	Q5AWS6	79.3%	Diamond
Schizosaccharomyces pombe 972h-	Q9P3A7	79.3%	Diamond
Saccharomyces cerevisiae S288C	P25694	75.7%	Diamond
Oryza sativa Japonica Group	Q0DGP6	73.8%	Diamond
Archaeoglobus fulgidus DSM 4304	O28972	68.8%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58556	67.0%	Diamond
Neurospora crassa OR74A	Q7SGP2	67.0%	Diamond
Colletotrichum orbiculare MAFF 240422	Q9C1E9	66.9%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SSJ5	60.8%	Diamond
Sulfolobus acidocaldarius DSM 639	Q07590	60.4%	Diamond
Thermoplasma acidophilum DSM 1728	O05209	59.6%	Diamond
Halobacterium salinarum NRC-1	Q9HPF0	57.6%	Diamond
Penicillium chrysogenum	Q9HG03	53.8%	Diamond
Ogataea angusta	Q9UVU5	53.7%	Diamond
Candida albicans	P34732	52.4%	Diamond
Orbilia oligospora ATCC 24927	G1X4S3	51.3%	Diamond
Yarrowia lipolytica CLIB122	P36966	51.1%	Diamond
Eremothecium gossypii ATCC 10895	Q74Z13	50.9%	Diamond
Debaryomyces hansenii CBS767	Q6BS73	50.6%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CPV1	50.6%	Diamond
Dictyostelium discoideum	Q54SY2	50.2%	Diamond
Plasmodium falciparum 3D7	P46468	49.6%	Diamond
Nakaseomyces glabratus CBS 138	Q6FW67	47.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ERVW-1	protein-coding	30816
GATAD1	protein-coding	57798
RBM48	protein-coding	84060
FAM133B	protein-coding	257415
CDK6	protein-coding	1021
ANKIB1	protein-coding	54467
KRIT1	protein-coding	889

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): A0A0C4DG33, H7BZH3, O43933

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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Transporters, Primary Active Transporters, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): peroxisomes

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
599–606	ATP
881–888	ATP

Post-translational modifications (4)

Type	Positions
Phosphoserine	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 peroxisomal membranes.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 2; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

2 pathways:

ID	Pathway	Evidence
R-HSA-9033241	Peroxisomal protein import	electronic
R-HSA-9609507	Protein localization	—

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 (5): cytoplasm (GO:0005737), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Protein localization	1

GO top-level categories

32 GO namespaces:

Category	Terms
establishment of protein localization to peroxisome	2
binding	2
cellular anatomical structure	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
anion 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
microtubule-based peroxisome localization	BP	mutant phenotype
peroxisome organization	BP	mutant phenotype
protein import into peroxisome matrix	BP	mutant phenotype
protein import into peroxisome matrix, receptor recycling	BP	direct assay
protein targeting to peroxisome	BP	mutant phenotype
protein unfolding	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
peroxisomal membrane	CC	direct assay
peroxisome	CC	direct assay
ATP binding	MF	mutant phenotype
ATP hydrolysis activity	MF	mutant phenotype
protein transporter activity	MF	direct assay
protein-containing complex binding	MF	direct assay
ubiquitin-modified protein reader activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 786 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX1	PEX5	P50542	893
PEX1	PEX2	P28328	879
PEX1	PEX26	Q7Z412	875
PEX1	PEX10	O60683	867
PEX1	PEX7	O00628	858
PEX1	PEX5L	Q8IYB4	854
PEX1	PEX12	O00623	850
PEX1	PEX19	P40855	841
PEX1	PEX13	Q92968	839
PEX1	PEX3	P56589	816
PEX1	PEX16	Q9Y5Y5	804
PEX1	PEX14	O75381	792
PEX1	TRIM37	O94972	699
PEX1	ABCD3	P28288	688
PEX1	AGPS	O00116	676

IntAct

Human interaction partners of PEX1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 48 partners by confidence:

Partner	Interaction type	MIscore	Records
ANAPC11	physical association	0.560	3
ANXA8	physical association	0.560	3
ARFGAP3	physical association	0.560	3
BATF	physical association	0.560	3
COPS3	physical association	0.560	3
DCAF8	physical association	0.560	3
DPYSL5	physical association	0.560	3
EIF5B	physical association	0.560	3
EPS8L1	physical association	0.560	3
GALNT6	physical association	0.560	3
H3C1	physical association	0.560	3
IFT20	physical association	0.560	3
ING4	physical association	0.560	3
KBTBD4	physical association	0.560	3
KLF3	physical association	0.560	3
KRT222	physical association	0.560	3
LHX8	physical association	0.560	3
MBIP	physical association	0.560	3
MNDA	physical association	0.560	3
MSH5	physical association	0.560	3
MYL11	physical association	0.560	3
PIAS1	physical association	0.560	3
PLPPR1	physical association	0.560	3
RHPN1	physical association	0.560	3
RYBP	physical association	0.560	3
SEMA4C	physical association	0.560	3
SEMA4G	physical association	0.560	3
SERINC3	physical association	0.560	3
SKIC8	physical association	0.560	3
SPATA8	physical association	0.560	3

BioGRID (116 interactions; top human partners by supporting records): PEX6 (Reconstituted Complex; 7 records), FAS (Affinity Capture-MS; 3 records), PEX26 (Affinity Capture-Western; 3 records), PEX5 (Reconstituted Complex; 3 records), DKKL1 (Affinity Capture-MS; 2 records), FAM174A (Affinity Capture-MS; 2 records), ICAM1 (Affinity Capture-MS; 2 records), ABCD3 (Co-localization), ACTC1 (Affinity Capture-MS), AKAP1 (Proximity Label-MS), ARRDC2 (Affinity Capture-MS), ARRDC4 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BRD1 (Affinity Capture-MS), C12orf74 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
AAA–ATPase complex, peroxisomal	3	PEX1, PEX26, PEX6

Disease & clinical

Genetic variants

Variant evidence for PEX1: 1,686 ClinVar records (309 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,686 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	120
Likely pathogenic	189
Uncertain significance	511
Likely benign	635
Benign	36

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 309 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
7516	NM_000466.3(PEX1):c.2528G>A (p.Gly843Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	49
7519	NM_000466.3(PEX1):c.2097dup (p.Ile700fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	45
265395	NM_000466.3(PEX1):c.2614C>T (p.Arg872Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
188910	NM_000466.3(PEX1):c.782_783del (p.Gln261fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
217430	NM_000466.3(PEX1):c.1239+1G>T	Pathogenic	criteria provided, multiple submitters, no conflicts	12
188971	NM_000466.3(PEX1):c.2730del (p.Leu910fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
188981	NM_000466.3(PEX1):c.3693_3696del (p.Gln1231fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
188984	NM_000466.3(PEX1):c.1716_1717del (p.His572fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
371692	NM_000466.3(PEX1):c.2034_2035del (p.His678fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
188897	NM_000466.3(PEX1):c.643_647del (p.Thr215fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
371727	NM_000466.3(PEX1):c.1670+1G>T	Pathogenic	criteria provided, multiple submitters, no conflicts	6
632939	NM_000466.3(PEX1):c.2368C>T (p.Arg790Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
550841	NM_000466.3(PEX1):c.1897C>T (p.Arg633Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
830062	NM_000466.3(PEX1):c.1483+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	4
937534	NM_000466.3(PEX1):c.2479C>T (p.Arg827Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4

Per-variant reference — Sugi Variant

Explore PEX1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,801):

Position(s)	Effect	Δscore	Sites
7:92487542–92487543	acceptor_loss	1.0000	4
7:92489291–92489292	donor_loss	1.0000	5
7:92489424–92489425	acceptor_loss	1.0000	4
7:92489425	acceptor_gain	1.0000
7:92491293	donor_gain	1.0000
7:92492947	donor_gain	1.0000
7:92493130–92493131	acceptor_loss	1.0000	6
7:92494397–92494398	acceptor_loss	1.0000	4
7:92494486	donor_gain	1.0000
7:92499702–92499703	donor_loss	1.0000	5

AlphaMissense

1,793 missense substitutions predicted likely pathogenic (of 8,397 scored), across 532 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D958	8	0.987	0.997
D990	8	0.987	0.996
D940	8	0.980	0.993
D952	8	0.977	0.995
D969	8	0.970	0.986
F926	8	0.948	0.989
F942	8	0.948	0.993
D1046	8	0.947	0.975
F938	8	0.935	0.987
N962	8	0.933	0.995
D783	8	0.931	0.968
F866	8	0.921	0.987
F939	8	0.921	0.986
D1000	8	0.909	0.967
S984	8	0.877	0.998
D854	8	0.798	0.915
D662	8	0.774	0.876
D813	8	0.770	0.844
H951	8	0.770	0.930
E941	7	0.983	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.12e-07
Thyroid Carcinoma (TCGA)	unfavorable	0.000798

Disease associations

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

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
peroxisome biogenesis disorder 1A (Zellweger)	Definitive	Autosomal recessive	2
peroxisome biogenesis disorder due to PEX1 defect	Definitive	Autosomal recessive	2
peroxisome biogenesis disorder	Definitive	Autosomal recessive	2
Heimler syndrome 1	Strong	Autosomal recessive	2
peroxisome biogenesis disorder 1B	Strong	Autosomal recessive	2
Zellweger spectrum disorders	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
peroxisome biogenesis disorder due to PEX1 defect	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (23 panels, 20 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

23 panels:

Panel	Rating
Amelogenesis imperfecta	green
Arthrogryposis	green
Bilateral congenital or childhood onset cataracts	green
Cerebral malformation	green
Cholestasis	green
DDG2P	green
Fetal anomalies	green
Fetal hydrops	green
Hypotonic infant	green
Inherited white matter disorders	green
Intellectual disability	green
Leukodystrophy, adult onset	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Malformations of cortical development	green
Neonatal cholestasis	green
Peroxisomal disorders	green
Retinal disorders	green
Undiagnosed metabolic disorders	green
White matter disorders and cerebral calcification - childhood onset	green
Early onset or syndromic epilepsy	amber
Paediatric disorders	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (10): Zellweger spectrum disorders (MONDO:0019609), peroxisome biogenesis disorder (MONDO:0019234), peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953), peroxisome biogenesis disorder due to PEX1 defect (MONDO:0100259), peroxisome biogenesis disorder 1B (MONDO:0011101), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998), peroxisomal disease (MONDO:0019053), optic atrophy (MONDO:0003608), (MONDO:0024544)

Orphanet (8): Zellweger syndrome (Orphanet:912), Deafness-enamel hypoplasia-nail defects syndrome (Orphanet:3220), Peroxisome biogenesis disorder (Orphanet:79189), Neonatal adrenoleukodystrophy (Orphanet:44), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Peroxisomal disease (Orphanet:68373), Infantile Refsum disease (Orphanet:772)

HPO phenotypes

showing 60 of 204 phenotypes (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:0000175	Cleft palate
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:0000325	Triangular face
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:0000444	Convex nasal ridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000492	Abnormal eyelid morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000532	Abnormal chorioretinal morphology
HP:0000534	Abnormal eyebrow morphology
HP:0000543	Optic disc pallor
HP:0000580	Pigmentary retinopathy
HP:0000582	Upslanted palpebral fissure
HP:0000614	Abnormal nasolacrimal system morphology
HP:0000627	Posterior embryotoxon
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000666	Horizontal nystagmus
HP:0000679	Taurodontia
HP:0000682	Abnormal dental enamel morphology
HP:0000705	Amelogenesis imperfecta
HP:0000708	Atypical behavior
HP:0000750	Delayed speech and language development
HP:0000763	Sensory neuropathy

GWAS associations

3 associations:

Study	Trait	p-value
GCST90020028_286	Hip circumference adjusted for BMI	5e-18
GCST90020028_404	Hip circumference adjusted for BMI	8e-10
GCST000175_26	Height	1e-8

EFO canonical traits (from GWAS)

1 canonical traits:

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

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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 (CPIC guideline: no)

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	increases oxidation, increases abundance, affects cotreatment	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	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Hydrogen Peroxide	affects expression	1
Lithium	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 88 trials:

NCT	Phase	Status	Title
NCT00007020	Phase 3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT01838941	Phase 3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00999609	Phase 3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	Phase 3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT02171104	Phase 2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	Phase 2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT03763227	Phase 2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	Phase 2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	Phase 2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01043640	Phase 2	COMPLETED	Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
NCT01064505	Phase 1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	Phase 1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT05902962	Phase 1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	Phase 1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	Phase 1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00516477	Phase 1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	Phase 1	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	Phase 2/3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	Phase 1/2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	Phase 1/2	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	Phase 2/3	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	Phase 1/2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	Phase 1/2	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	Phase 1/2	ACTIVE_NOT_RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	Phase 1/2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	Phase 1/2	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	Phase 1/2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	Early Phase 1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT07656753	Early Phase 1	RECRUITING	Safety and Efficacy Study of PUMCH-E111 Injection in Subjects With RLBP1 Related Inherited Retinal Dystrophy
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)