peroxisome biogenesis disorder due to PEX1 defect

Summary

peroxisome biogenesis disorder due to PEX1 defect (MONDO:0100259) is a disease caused by PEX1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PEX1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder due to PEX1 defect
Mondo ID	MONDO:0100259
OMIM	234580
GARD	0026101
Is cancer (heuristic)	no

Also known as: peroxisome biogenesis disorder due to PEX1 defect · PEX1 related Zellweger spectrum disorder

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

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 PEX1 defect

Related subtypes (14): peroxisome biogenesis disorder 9B, 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

Subtypes (2): peroxisome biogenesis disorder 1A (Zellweger), peroxisome biogenesis disorder 1B

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

6 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 pathogenic/likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324877	NM_000466.3(PEX1):c.1099del (p.Gln367fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189043	NM_000466.3(PEX1):c.2916del (p.Gly973fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
593271	NM_000466.3(PEX1):c.2396dup (p.Ser800fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
7516	NM_000466.3(PEX1):c.2528G>A (p.Gly843Asp)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
502697	NM_000466.3(PEX1):c.3283G>A (p.Asp1095Asn)	GATAD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805328	NM_000466.3(PEX1):c.3085G>T (p.Asp1029Tyr)	GATAD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · 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

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
GATAD1	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX1	HGNC:8850	ENSG00000127980	O43933	Peroxisomal ATPase PEX1	gencc,clinvar
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.
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: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.228
Transcription factor	1	4.1×	0.228

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
GATAD1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, GATAD1

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
calcaneal tendon	1
mucosa of stomach	1
inferior vagus X ganglion	1
left ovary	1
right uterine tube	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
GATAD1	287	ubiquitous	marker	left ovary, right uterine tube, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX1	2,413
GATAD1	1,065

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GATAD1	Q8WUU5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX1	O43933	67.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Peroxisomal protein import	1	173.0×	0.006	PEX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
microtubule-based peroxisome localization	1	4213.0×	0.002	PEX1
protein unfolding	1	1685.2×	0.002	PEX1
protein import into peroxisome matrix, receptor recycling	1	1203.7×	0.002	PEX1
protein targeting to peroxisome	1	842.6×	0.003	PEX1
protein import into peroxisome matrix	1	702.2×	0.003	PEX1
peroxisome organization	1	401.2×	0.004	PEX1
chromatin organization	1	49.6×	0.026	GATAD1
chromatin remodeling	1	36.5×	0.031	GATAD1
regulation of DNA-templated transcription	1	15.8×	0.062	GATAD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
PEX1	0	0
GATAD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PEX1	3.6.4.7	peroxisome-assembly ATPase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	PEX1
E	Difficult family or no structure, no drug	1	GATAD1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PEX1	0	—
GATAD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.