peroxisome biogenesis disorder due to PEX5 defect

Summary

peroxisome biogenesis disorder due to PEX5 defect (MONDO:0100262) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder due to PEX5 defect
Mondo ID	MONDO:0100262
GARD	0026104
Is cancer (heuristic)	no

Also known as: peroxisome biogenesis disorder due to PEX5 defect · PEX5 related Zellweger spectrum disorder

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › Zellweger spectrum disorders › peroxisome biogenesis disorder due to PEX5 defect

Related subtypes (14): 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 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

Subtypes (2): peroxisome biogenesis disorder 2B, peroxisome biogenesis disorder 2A (Zellweger)

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2412727	NM_001351132.2(PEX5):c.138del (p.Ser47fs)	PEX5	Likely pathogenic	criteria provided, single submitter
2412728	NM_001351132.2(PEX5):c.140_147+36del	PEX5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX5	Orphanet:44	Neonatal adrenoleukodystrophy
PEX5	Orphanet:468717	Rhizomelic chondrodysplasia punctata type 5
PEX5	Orphanet:772	Infantile Refsum disease
PEX5	Orphanet:912	Zellweger syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX5	HGNC:9719	ENSG00000139197	P50542	Peroxisomal targeting signal 1 receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX5	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, PEX5/PEX5L

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX5	142	ubiquitous	marker	gastrocnemius, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX5	1,741

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX5	P50542	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Pexophagy	1	951.7×	0.003	PEX5
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX5
Peroxisomal protein import	1	173.0×	0.006	PEX5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein import into peroxisome matrix, docking	1	4213.0×	0.001	PEX5
protein import into peroxisome matrix, translocation	1	4213.0×	0.001	PEX5
protein import into peroxisome matrix, substrate release	1	3370.4×	0.001	PEX5
protein import into peroxisome membrane	1	2808.7×	0.001	PEX5
mitochondrial membrane organization	1	2407.4×	0.001	PEX5
protein import into peroxisome matrix, receptor recycling	1	2407.4×	0.001	PEX5
protein targeting to peroxisome	1	1685.2×	0.002	PEX5
cerebral cortex cell migration	1	1532.0×	0.002	PEX5
protein import into peroxisome matrix	1	1404.3×	0.002	PEX5
cerebral cortex neuron differentiation	1	1203.7×	0.002	PEX5
pexophagy	1	1053.2×	0.002	PEX5
cell development	1	887.0×	0.002	PEX5
very long-chain fatty acid metabolic process	1	766.0×	0.002	PEX5
protein tetramerization	1	624.1×	0.002	PEX5
neuromuscular process	1	526.6×	0.003	PEX5
positive regulation of multicellular organism growth	1	495.6×	0.003	PEX5
negative regulation of protein-containing complex assembly	1	455.5×	0.003	PEX5
endoplasmic reticulum organization	1	421.3×	0.003	PEX5
cellular response to reactive oxygen species	1	411.0×	0.003	PEX5
fatty acid beta-oxidation	1	374.5×	0.003	PEX5
neuron migration	1	133.8×	0.007	PEX5

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEX5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
E	Difficult family or no structure, no drug	1	PEX5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PEX5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.