Zellweger spectrum disorders

Summary

Zellweger spectrum disorders (MONDO:0019609) is a disease (an umbrella term covering 15 Mondo subtypes) with 14 cohort genes and 6 clinical trials. The dominant Reactome pathway is Class I peroxisomal membrane protein import (9 cohort genes). Top therapeutic interventions include chenodiol, cholic acid, and hydroxychloroquine.

At a glance

• Prevalence: 1-9 / 100 000 (Specific population) [Orphanet-validated]
• Umbrella term: 15 Mondo subtypes
• Cohort genes: 14
• ClinVar variants: 2,191
• Phenotypes (HPO): 55
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	8.2	Specific population	Validated
Prevalence at birth	1-9 / 100 000	4.6	Israel	Validated
Prevalence at birth	1-9 / 100 000	8.2	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

55 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000377	Abnormal pinna morphology	Very frequent (80-99%)
HP:0001522	Death in infancy	Very frequent (80-99%)
HP:0002093	Respiratory insufficiency	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0002353	EEG abnormality	Very frequent (80-99%)
HP:0002652	Skeletal dysplasia	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0006829	Severe muscular hypotonia	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0008167	Very long chain fatty acid accumulation	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0010655	Epiphyseal stippling	Very frequent (80-99%)
HP:0012368	Flat face	Very frequent (80-99%)
HP:0012736	Profound global developmental delay	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)
HP:0000260	Wide anterior fontanel	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000348	High forehead	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000582	Upslanted palpebral fissure	Very frequent (80-99%)
HP:0000952	Jaundice	Very frequent (80-99%)
HP:0001315	Reduced tendon reflexes	Very frequent (80-99%)
HP:0001399	Hepatic failure	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0000003	Multicystic kidney dysplasia	Frequent (30-79%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000126	Hydronephrosis	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000532	Chorioretinal abnormality	Frequent (30-79%)
HP:0000627	Posterior embryotoxon	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001622	Premature birth	Frequent (30-79%)
HP:0002021	Pyloric stenosis	Frequent (30-79%)
HP:0002024	Malabsorption	Frequent (30-79%)
HP:0002126	Polymicrogyria	Frequent (30-79%)
HP:0005469	Flat occiput	Frequent (30-79%)
HP:0008665	Clitoral hypertrophy	Frequent (30-79%)
HP:0009891	Underdeveloped supraorbital ridges	Frequent (30-79%)
HP:0000157	Abnormality of the tongue	Occasional (5-29%)
HP:0000474	Thickened nuchal skin fold	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Zellweger spectrum disorders
Mondo ID	MONDO:0019609
MeSH	D015211
Orphanet	912, 772
DOID	DOID:905
ICD-10-CM	E71.510
NCIT	C85239
SNOMED CT	88469006
UMLS	C0043459
MedGen	21958
GARD	0007917
NORD	1876
Is cancer (heuristic)	no

Also known as: cerebrohepatorenal syndrome · Zellweger leukodystrophy · Zellweger spectrum disorders · Zellweger syndrome · ZS · ZWS

Data availability: 2,191 ClinVar variants · 13 GenCC gene-disease records · 17 cell lines.

Disease family

An umbrella term covering 15 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › Zellweger spectrum disorders

Related subtypes (56): Neu-Laxova syndrome, inborn mitochondrial metabolism disorder, Ehlers-Danlos syndrome, spondylodysplastic type, MGAT2-congenital disorder of glycosylation, ALDH18A1-related de Barsy syndrome, classic homocystinuria, Larsen-like syndrome, B3GAT3 type, Nijmegen breakage syndrome, Peters plus syndrome, Wiedemann-Rautenstrauch syndrome, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, SHORT syndrome, mucosulfatidosis, CHIME syndrome, creatine transporter deficiency, multiple congenital anomalies-hypotonia-seizures syndrome 2, SLC35A2-congenital disorder of glycosylation, SSR4-congenital disorder of glycosylation, Fabry disease, occipital horn syndrome, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, B4GALT1-congenital disorder of glycosylation, AICA-ribosiduria, COG7-congenital disorder of glycosylation, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, Al-Gazali syndrome, COG1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, Nijmegen breakage syndrome-like disorder, multiple congenital anomalies-hypotonia-seizures syndrome 1, multiple congenital anomalies-hypotonia-seizures syndrome 3, autism spectrum disorder - epilepsy - arthrogryposis syndrome, cutis laxa, autosomal dominant 3, SLC39A8-CDG, transketolase deficiency, mucopolysaccharidosis-plus syndrome, Cockayne syndrome, pontocerebellar hypoplasia type 1, mandibuloacral dysplasia, hyperphosphatasia-intellectual disability syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, CADDS, XYLT1-congenital disorder of glycosylation, hypophosphatasia, sterol biosynthesis disorder, mucolipidosis, mucopolysaccharidosis, oligosaccharidosis, encephalopathy due to sulfite oxidase deficiency, Fanconi anemia, autosomal recessive cutis laxa type 2, pseudohypoparathyroidism, developmental and epileptic encephalopathy, 77, glycosylphosphatidylinositol biosynthesis defect 15, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN

Subtypes (15): peroxisome biogenesis disorder 9B, peroxisome biogenesis disorder due to PEX1 defect, peroxisome biogenesis disorder due to PEX2 defect, peroxisome biogenesis disorder due to PEX3 defect, peroxisome biogenesis disorder due to PEX5 defect, peroxisome biogenesis disorder due to PEX6 defect, peroxisome biogenesis disorder due to PEX10 defect, peroxisome biogenesis disorder due to PEX12 defect, peroxisome biogenesis disorder due to PEX13 defect, peroxisome biogenesis disorder due to PEX14 defect, peroxisome biogenesis disorder due to PEX16 defect, peroxisome biogenesis disorder due to PEX19 defect, peroxisome biogenesis disorder due to PEX26 defect, peroxisome biogenesis disorder due to PEX11B defect, peroxisome biogenesis disorder, complementation group 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

304 likely benign, 189 uncertain significance, 36 pathogenic/likely pathogenic, 32 pathogenic, 15 conflicting classifications of pathogenicity, 11 benign, 10 likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066589	NM_000466.3(PEX1):c.3207+1G>C	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069980	NM_000466.3(PEX1):c.3158dup (p.Asn1053fs)	GATAD1	Pathogenic	criteria provided, single submitter
1415183	NM_000466.3(PEX1):c.2977dup (p.Leu993fs)	GATAD1	Pathogenic	criteria provided, single submitter
1451521	NM_000466.3(PEX1):c.56_80del (p.Val19fs)	LOC129998796	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068549	NM_000466.3(PEX1):c.1456G>T (p.Glu486Ter)	PEX1	Pathogenic	criteria provided, single submitter
1068947	NM_000466.3(PEX1):c.3258del (p.Asn1088fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069047	NM_000466.3(PEX1):c.3037C>T (p.Arg1013Cys)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070094	NM_000466.3(PEX1):c.2550dup (p.Ile851fs)	PEX1	Pathogenic	criteria provided, single submitter
1070573	NM_000466.3(PEX1):c.3450T>A (p.Cys1150Ter)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070990	NM_000466.3(PEX1):c.2738_2741dup (p.Tyr914Ter)	PEX1	Pathogenic	criteria provided, single submitter
1074109	NC_000007.13:g.(?92148299)(92157759_?)del	PEX1	Pathogenic	criteria provided, single submitter
1074539	NM_000466.3(PEX1):c.2692_2693del (p.Glu897_Ser898insTer)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076872	NM_000466.3(PEX1):c.3301G>T (p.Glu1101Ter)	PEX1	Pathogenic	criteria provided, single submitter
1098755	NM_000466.3(PEX1):c.788_789del (p.Thr263fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
1098815	NM_000466.3(PEX1):c.130-2A>T	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323432	NM_000466.3(PEX1):c.2083_2084del (p.Met695fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
1324876	NM_000466.3(PEX1):c.1411C>T (p.Gln471Ter)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324877	NM_000466.3(PEX1):c.1099del (p.Gln367fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324879	NM_000466.3(PEX1):c.1393_1394del (p.Val465fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1363179	NM_000466.3(PEX1):c.3152_3156del (p.Leu1051fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1380467	NM_000466.3(PEX1):c.2516G>A (p.Trp839Ter)	PEX1	Pathogenic	criteria provided, single submitter
1384557	NM_000466.3(PEX1):c.3259_3260del (p.Phe1086_Leu1087insTer)	PEX1	Pathogenic	criteria provided, single submitter
1395451	NC_000007.14:g.92528411_92528711del	PEX1	Pathogenic	criteria provided, single submitter
1403359	NM_000466.3(PEX1):c.2039del (p.Pro680fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1403370	NM_000466.3(PEX1):c.955C>T (p.Gln319Ter)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404596	NM_000466.3(PEX1):c.2164del (p.Val723fs)	PEX1	Pathogenic	criteria provided, single submitter
1404606	NM_000466.3(PEX1):c.2162T>A (p.Leu721Ter)	PEX1	Pathogenic	criteria provided, single submitter
1422035	NM_000466.3(PEX1):c.1795G>T (p.Gly599Ter)	PEX1	Pathogenic	criteria provided, single submitter
1423136	NM_000466.3(PEX1):c.1916dup (p.Asn639fs)	PEX1	Pathogenic	criteria provided, single submitter
1428826	NM_000466.3(PEX1):c.3005_3011dup (p.Tyr1004Ter)	PEX1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 94 · Orphanet: 47 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PEX1	Definitive	Autosomal recessive	peroxisome biogenesis disorder 1A (Zellweger)	9
PEX10	Definitive	Autosomal recessive	peroxisome biogenesis disorder 6A (Zellweger)	10
PEX12	Definitive	Autosomal recessive	peroxisome biogenesis disorder 3A (Zellweger)	7
PEX13	Definitive	Autosomal recessive	peroxisome biogenesis disorder 11A (Zellweger)	5
PEX14	Definitive	Autosomal recessive	peroxisome biogenesis disorder 13A (Zellweger)	6
PEX16	Definitive	Autosomal recessive	peroxisome biogenesis disorder 8A (Zellweger)	7
PEX19	Definitive	Autosomal recessive	peroxisome biogenesis disorder 12A (Zellweger)	4
PEX2	Definitive	Autosomal recessive	peroxisome biogenesis disorder 5A (Zellweger)	8
PEX26	Definitive	Autosomal recessive	peroxisome biogenesis disorder 7A (Zellweger)	7
PEX3	Definitive	Autosomal recessive	peroxisome biogenesis disorder 10A (Zellweger)	6
PEX5	Definitive	Autosomal recessive	peroxisome biogenesis disorder 2A (Zellweger)	10
PEX6	Definitive	Autosomal recessive	peroxisome biogenesis disorder 4A (Zellweger)	10
PEX11B	Supportive	Autosomal recessive	Zellweger spectrum disorders	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX1	Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome
PEX1	Orphanet:44	Neonatal adrenoleukodystrophy
PEX1	Orphanet:772	Infantile Refsum disease
PEX1	Orphanet:912	Zellweger syndrome
PEX10	Orphanet:247815	Autosomal recessive ataxia due to PEX10 deficiency
PEX10	Orphanet:44	Neonatal adrenoleukodystrophy
PEX10	Orphanet:772	Infantile Refsum disease
PEX10	Orphanet:912	Zellweger syndrome
PEX6	Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome
PEX6	Orphanet:44	Neonatal adrenoleukodystrophy
PEX6	Orphanet:772	Infantile Refsum disease
PEX6	Orphanet:912	Zellweger syndrome
PEX6	Orphanet:95433	Autosomal recessive spinocerebellar ataxia-blindness-deafness syndrome
PEX19	Orphanet:44	Neonatal adrenoleukodystrophy
PEX19	Orphanet:772	Infantile Refsum disease
PEX19	Orphanet:912	Zellweger syndrome
PEX2	Orphanet:44	Neonatal adrenoleukodystrophy
PEX2	Orphanet:642965	Autosomal recessive ataxia due to PEX2 deficiency
PEX2	Orphanet:772	Infantile Refsum disease
PEX2	Orphanet:912	Zellweger syndrome
PEX5	Orphanet:44	Neonatal adrenoleukodystrophy
PEX5	Orphanet:468717	Rhizomelic chondrodysplasia punctata type 5
PEX5	Orphanet:772	Infantile Refsum disease
PEX5	Orphanet:912	Zellweger syndrome
PEX26	Orphanet:44	Neonatal adrenoleukodystrophy
PEX26	Orphanet:772	Infantile Refsum disease
PEX26	Orphanet:912	Zellweger syndrome
PEX11B	Orphanet:44	Neonatal adrenoleukodystrophy
PEX11B	Orphanet:772	Infantile Refsum disease
PEX11B	Orphanet:912	Zellweger syndrome
PEX12	Orphanet:44	Neonatal adrenoleukodystrophy
PEX12	Orphanet:772	Infantile Refsum disease
PEX12	Orphanet:912	Zellweger syndrome
PEX13	Orphanet:44	Neonatal adrenoleukodystrophy
PEX13	Orphanet:772	Infantile Refsum disease
PEX13	Orphanet:912	Zellweger syndrome
PEX14	Orphanet:44	Neonatal adrenoleukodystrophy
PEX14	Orphanet:772	Infantile Refsum disease
PEX14	Orphanet:912	Zellweger syndrome
PEX16	Orphanet:44	Neonatal adrenoleukodystrophy
PEX16	Orphanet:642954	Autosomal recessive ataxia due to PEX16 deficiency
PEX16	Orphanet:772	Infantile Refsum disease
PEX16	Orphanet:912	Zellweger syndrome
PEX3	Orphanet:44	Neonatal adrenoleukodystrophy
PEX3	Orphanet:772	Infantile Refsum disease
PEX3	Orphanet:912	Zellweger syndrome
GATAD1	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

14 cohort genes, 14 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX1	HGNC:8850	ENSG00000127980	O43933	Peroxisomal ATPase PEX1	gencc,clinvar
PEX10	HGNC:8851	ENSG00000157911	O60683	Peroxisome biogenesis factor 10	gencc,clinvar
PEX6	HGNC:8859	ENSG00000124587	Q13608	Peroxisomal ATPase PEX6	gencc,clinvar
PEX19	HGNC:9713	ENSG00000162735	P40855	Peroxisomal biogenesis factor 19	gencc,clinvar
PEX2	HGNC:9717	ENSG00000164751	P28328	Peroxisome biogenesis factor 2	gencc,clinvar
PEX5	HGNC:9719	ENSG00000139197	P50542	Peroxisomal targeting signal 1 receptor	gencc,clinvar
PEX26	HGNC:22965	ENSG00000215193	Q7Z412	Peroxisome assembly protein 26	gencc
PEX11B	HGNC:8853	ENSG00000131779	O96011	Peroxisomal membrane protein 11B	gencc
PEX12	HGNC:8854	ENSG00000108733	O00623	Peroxisome assembly protein 12	gencc
PEX13	HGNC:8855	ENSG00000162928	Q92968	Peroxisomal membrane protein PEX13	gencc
PEX14	HGNC:8856	ENSG00000142655	O75381	Peroxisomal membrane protein PEX14	gencc
PEX16	HGNC:8857	ENSG00000121680	Q9Y5Y5	Peroxisomal membrane protein PEX16	gencc
PEX3	HGNC:8858	ENSG00000034693	P56589	Peroxisomal biogenesis factor 3	gencc
GATAD1	HGNC:29941	ENSG00000157259	Q8WUU5	GATA zinc finger domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX1	Peroxisomal ATPase PEX1	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.
PEX10	Peroxisome biogenesis factor 10	E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
PEX6	Peroxisomal ATPase PEX6	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.
PEX19	Peroxisomal biogenesis factor 19	Necessary for early peroxisomal biogenesis.
PEX2	Peroxisome biogenesis factor 2	E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
PEX5	Peroxisomal targeting signal 1 receptor	Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type).
PEX26	Peroxisome assembly protein 26	Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes.
PEX11B	Peroxisomal membrane protein 11B	Involved in peroxisomal proliferation.
PEX12	Peroxisome assembly protein 12	Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
PEX13	Peroxisomal membrane protein PEX13	Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.
PEX14	Peroxisomal membrane protein PEX14	Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.
PEX16	Peroxisomal membrane protein PEX16	Required for peroxisome membrane biogenesis.
PEX3	Peroxisomal biogenesis factor 3	Involved in peroxisome biosynthesis and integrity.
GATAD1	GATA zinc finger domain-containing protein 1	Component of some chromatin complex recruited to chromatin sites methylated ‘Lys-4’ of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).

Protein-family classification

Druggable: 2 · Difficult: 5 · Unknown: 7 · Druggable fraction: 0.14

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	4	2.4×	0.318
Enzyme (other)	2	1.7×	0.656
Scaffold/PPI	1	1.2×	0.754
Other/Unknown	7	0.9×	0.761

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX1	Enzyme (other)	yes	3.6.4.7	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
PEX10	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD
PEX6	Enzyme (other)	yes	3.6.4.7	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
PEX19	Other/Unknown	no		Pex19, Pex19_C_sf
PEX2	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD
PEX5	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, PEX5/PEX5L
PEX26	Other/Unknown	no		Pex26
PEX11B	Other/Unknown	no		PEX11
PEX12	Transcription factor	no		Pex_N, Znf_RING/FYVE/PHD, PEX12
PEX13	Scaffold/PPI	no		SH3_domain, Peroxin-13_N, Pex13
PEX14	Other/Unknown	no		Pex14_N, PEX14, WH-like_DNA-bd_sf
PEX16	Other/Unknown	no		Pex16
PEX3	Other/Unknown	no		Peroxin-3
GATAD1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, GATAD1

Expression context

Cohort genes with no expression data: 0.

13 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	2
tendon of biceps brachii	2
mucosa of transverse colon	2
right uterine tube	2
gastrocnemius	2
prefrontal cortex	2
secondary oocyte	2
calcaneal tendon	1
mucosa of stomach	1
C1 segment of cervical spinal cord	1
parotid gland	1
hindlimb stylopod muscle	1
muscle of leg	1
olfactory segment of nasal mucosa	1
seminal vesicle	1
ventricular zone	1
left testis	1
right testis	1
cortical plate	1
Brodmann (1909) area 9	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX1	279	ubiquitous	marker	calcaneal tendon, body of pancreas, mucosa of stomach
PEX10	266	ubiquitous	marker	parotid gland, tendon of biceps brachii, C1 segment of cervical spinal cord
PEX6	227	ubiquitous	marker	right uterine tube, body of pancreas, mucosa of transverse colon
PEX19	282	ubiquitous	marker	hindlimb stylopod muscle, muscle of leg, gastrocnemius
PEX2	291	ubiquitous	marker	seminal vesicle, ventricular zone, olfactory segment of nasal mucosa
PEX5	142	ubiquitous	marker	gastrocnemius, left testis, right testis
PEX26	253	ubiquitous	marker	mucosa of transverse colon, tendon of biceps brachii, cortical plate
PEX11B	289	ubiquitous	marker	prefrontal cortex, Brodmann (1909) area 9, medial globus pallidus
PEX12	270	ubiquitous	yes	secondary oocyte, choroid plexus epithelium, primordial germ cell in gonad
PEX13	264	ubiquitous	marker	secondary oocyte, sperm, oocyte
PEX14	286	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
PEX16	281	ubiquitous	marker	prefrontal cortex, granulocyte, right lobe of liver
PEX3	291	ubiquitous	marker	adrenal tissue, endothelial cell, right adrenal gland cortex
GATAD1	287	ubiquitous	marker	left ovary, right uterine tube, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 76.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX6	2,620
PEX19	2,544
PEX1	2,413
PEX3	1,838
PEX5	1,741
PEX11B	1,331
PEX14	1,273
PEX16	1,231
PEX13	1,127
PEX10	1,117

Intra-cohort edges

A	B	Sources
PEX1	PEX10	string_interaction
PEX1	PEX12	string_interaction
PEX1	PEX13	string_interaction
PEX1	PEX14	string_interaction
PEX1	PEX16	string_interaction
PEX1	PEX19	string_interaction
PEX1	PEX2	string_interaction
PEX1	PEX26	biogrid_interaction, string_interaction
PEX1	PEX3	string_interaction
PEX1	PEX5	string_interaction
PEX1	PEX6	biogrid_interaction, intact
PEX10	PEX11B	string_interaction
PEX10	PEX12	biogrid_interaction, string_interaction
PEX10	PEX13	string_interaction
PEX10	PEX14	intact, string_interaction
PEX10	PEX16	string_interaction
PEX10	PEX19	intact, string_interaction
PEX10	PEX2	biogrid_interaction, string_interaction
PEX10	PEX26	string_interaction
PEX10	PEX3	string_interaction
PEX10	PEX5	biogrid_interaction, intact, string_interaction
PEX10	PEX6	string_interaction
PEX11B	PEX12	string_interaction
PEX11B	PEX13	string_interaction
PEX11B	PEX14	string_interaction
PEX11B	PEX16	string_interaction
PEX11B	PEX19	biogrid_interaction, intact, string_interaction
PEX11B	PEX2	string_interaction
PEX11B	PEX3	string_interaction
PEX11B	PEX5	string_interaction
PEX11B	PEX6	string_interaction
PEX12	PEX13	string_interaction
PEX12	PEX14	string_interaction
PEX12	PEX16	string_interaction
PEX12	PEX19	string_interaction
PEX12	PEX2	intact, string_interaction
PEX12	PEX26	string_interaction
PEX12	PEX3	string_interaction
PEX12	PEX5	biogrid_interaction, intact, string_interaction
PEX12	PEX6	string_interaction
PEX13	PEX14	biogrid_interaction, intact, string_interaction
PEX13	PEX16	string_interaction
PEX13	PEX19	intact, string_interaction
PEX13	PEX2	string_interaction
PEX13	PEX26	string_interaction
PEX13	PEX3	string_interaction
PEX13	PEX5	biogrid_interaction, string_interaction
PEX13	PEX6	string_interaction
PEX14	PEX16	string_interaction
PEX14	PEX19	intact, string_interaction

Structural data

PDB: 6 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX5	P50542	11
PEX19	P40855	5
PEX14	O75381	4
PEX13	Q92968	3
PEX3	P56589	2
GATAD1	Q8WUU5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX11B	O96011	90.12
PEX16	Q9Y5Y5	83.07
PEX10	O60683	82.81
PEX12	O00623	81.58
PEX2	P28328	81.17
PEX26	Q7Z412	79.87
PEX6	Q13608	69.87
PEX1	O43933	67.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 14 evidence-associated genes (13 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class I peroxisomal membrane protein import	9	359.4×	2e-22	PEX19, PEX2, PEX26, PEX11B, PEX12, PEX13, PEX14, PEX16 (+1 more)
Peroxisomal protein import	9	119.8×	9e-18	PEX1, PEX10, PEX6, PEX2, PEX5, PEX26, PEX12, PEX13 (+1 more)
E3 ubiquitin ligases ubiquitinate target proteins	6	89.3×	5e-11	PEX10, PEX2, PEX5, PEX12, PEX13, PEX14
ABC transporters in lipid homeostasis	2	92.5×	3e-04	PEX19, PEX3
Pexophagy	1	73.2×	0.016	PEX5
Dengue Virus-Host Interactions	1	3.5×	0.250	PEX19

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peroxisome organization	10	573.2×	4e-26	PEX1, PEX10, PEX6, PEX19, PEX2, PEX11B, PEX12, PEX14 (+2 more)
protein import into peroxisome matrix	9	902.8×	4e-26	PEX1, PEX10, PEX6, PEX2, PEX5, PEX26, PEX12, PEX14 (+1 more)
protein import into peroxisome matrix, receptor recycling	6	1031.8×	1e-17	PEX1, PEX10, PEX6, PEX2, PEX5, PEX12
protein targeting to peroxisome	6	722.2×	3e-16	PEX1, PEX6, PEX19, PEX5, PEX12, PEX16
protein import into peroxisome matrix, substrate release	5	1203.7×	2e-15	PEX10, PEX2, PEX5, PEX12, PEX14
protein import into peroxisome membrane	5	1003.1×	1e-14	PEX19, PEX5, PEX26, PEX16, PEX3
protein import into peroxisome matrix, translocation	4	1203.7×	2e-12	PEX6, PEX5, PEX13, PEX14
cellular response to reactive oxygen species	6	176.2×	3e-12	PEX10, PEX2, PEX5, PEX12, PEX13, PEX14
protein import into peroxisome matrix, docking	3	902.8×	1e-08	PEX5, PEX13, PEX14
microtubule-based peroxisome localization	2	1203.7×	4e-06	PEX1, PEX13
peroxisome membrane biogenesis	2	802.5×	1e-05	PEX19, PEX16
protein to membrane docking	2	481.5×	3e-05	PEX26, PEX16
protein unfolding	2	481.5×	3e-05	PEX1, PEX6
peroxisome fission	2	218.9×	1e-04	PEX19, PEX11B
cerebral cortex cell migration	2	218.9×	1e-04	PEX5, PEX13
pexophagy	2	150.5×	3e-04	PEX2, PEX5
very long-chain fatty acid metabolic process	2	109.4×	4e-04	PEX2, PEX5
protein quality control for misfolded or incompletely synthesized proteins	2	109.4×	4e-04	PEX10, PEX12
fatty acid beta-oxidation	2	53.5×	0.002	PEX2, PEX5
ER-dependent peroxisome organization	1	1203.7×	0.002	PEX16
peroxisome transport along microtubule	1	1203.7×	0.002	PEX14
establishment of protein localization to peroxisome	1	1203.7×	0.002	PEX19
ER-dependent peroxisome localization	1	1203.7×	0.002	PEX16
negative regulation of lipid binding	1	1203.7×	0.002	PEX19
protein monoubiquitination	2	49.1×	0.002	PEX2, PEX12
regulation of peroxisome size	1	401.2×	0.005	PEX11B
response to amino acid starvation	1	300.9×	0.007	PEX2
neuron migration	2	19.1×	0.009	PEX5, PEX13
fatty acid alpha-oxidation	1	172.0×	0.011	PEX13
mitochondrial membrane organization	1	172.0×	0.011	PEX5

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Hydroxychloroquine.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 14

Druggability breadth: 4 of 14 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEX1	0	0
PEX10	0	0
PEX6	0	0
PEX19	0	0
PEX2	0	0
PEX5	0	0
PEX26	0	0
PEX11B	0	0
PEX12	0	0
PEX13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PEX2	1	Binding:1
PEX14	1	ADMET:1
PEX16	1	Binding:1
PEX3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PEX1	3.6.4.7	peroxisome-assembly ATPase
PEX6	3.6.4.7	peroxisome-assembly ATPase

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	PEX1, PEX6
E	Difficult family or no structure, no drug	12	PEX10, PEX19, PEX2, PEX5, PEX26, PEX11B, PEX12, PEX13, PEX14, PEX16 (+2 more)

Undrugged target profiles

14 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PEX1	0	—
PEX10	0	—
PEX6	0	—
PEX19	0	—
PEX2	1	—
PEX5	0	—
PEX26	0	—
PEX11B	0	—
PEX12	0	—
PEX13	0	—
PEX14	1	—
PEX16	1	—
PEX3	1	—
GATAD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHENODIOL	4	1
CHOLIC ACID	4	1
HYDROXYCHLOROQUINE	4	1
URSODIOL	4	1