peroxisome biogenesis disorder 10A (Zellweger)

Summary

peroxisome biogenesis disorder 10A (Zellweger) (MONDO:0013948) is a disease caused by PEX3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PEX3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 60

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 10A (Zellweger)
Mondo ID	MONDO:0013948
OMIM	614882
DOID	DOID:0080484
UMLS	C3553999
MedGen	766913
GARD	0015873
Is cancer (heuristic)	no

Also known as: PBD10A · peroxisome biogenesis disorder 10A (Zellweger)

Data availability: 60 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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 PEX3 defect › peroxisome biogenesis disorder 10A (Zellweger)

Related subtypes (1): peroxisome biogenesis disorder 10B

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

60 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 8 conflicting classifications of pathogenicity, 6 benign, 4 likely pathogenic, 3 benign/likely benign, 3 likely benign, 2 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
597138	NM_003630.3(PEX3):c.288-1G>A	PEX3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
631556	NM_003630.3(PEX3):c.942-8T>G	PEX3	Pathogenic	criteria provided, single submitter
6618	NM_003630.3(PEX3):c.543dup (p.Val182fs)	PEX3	Pathogenic	no assertion criteria provided
973435	NM_003630.3(PEX3):c.292_302del (p.Ser98fs)	PEX3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065621	NM_003630.3(PEX3):c.844A>C (p.Thr282Pro)	PEX3	Likely pathogenic	criteria provided, single submitter
2627431	NM_003630.3(PEX3):c.144C>A (p.Tyr48Ter)	PEX3	Likely pathogenic	criteria provided, single submitter
3065043	NM_003630.3(PEX3):c.74G>T (p.Gly25Val)	PEX3	Likely pathogenic	criteria provided, single submitter
3593211	NM_003630.3(PEX3):c.-4_12del (p.Met1fs)	PEX3	Likely pathogenic	criteria provided, single submitter
195197	NM_003630.3(PEX3):c.165A>G (p.Gln55=)	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289544	NM_003630.3(PEX3):c.578+8A>G	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291279	NM_003630.3(PEX3):c.473C>G (p.Pro158Arg)	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355573	NM_003630.3(PEX3):c.51C>T (p.Ile17=)	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355574	NM_003630.3(PEX3):c.96T>C (p.Tyr32=)	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355576	NM_003630.3(PEX3):c.249A>G (p.Gln83=)	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355579	NM_003630.3(PEX3):c.*220G>A	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906787	NM_003630.3(PEX3):c.332-9T>A	PEX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029734	NM_003630.3(PEX3):c.1048A>C (p.Thr350Pro)	PEX3	Uncertain significance	criteria provided, single submitter
1366095	NM_003630.3(PEX3):c.553C>A (p.Gln185Lys)	PEX3	Uncertain significance	criteria provided, single submitter
355568	NM_003630.3(PEX3):c.-214G>C	PEX3	Uncertain significance	criteria provided, single submitter
355571	NM_003630.3(PEX3):c.-175G>C	PEX3	Uncertain significance	criteria provided, single submitter
355577	NM_003630.3(PEX3):c.887C>T (p.Ala296Val)	PEX3	Uncertain significance	criteria provided, single submitter
355578	NM_003630.3(PEX3):c.*129C>T	PEX3	Uncertain significance	criteria provided, single submitter
355584	NM_003630.3(PEX3):c.*424T>C	PEX3	Uncertain significance	criteria provided, single submitter
355586	NM_003630.3(PEX3):c.*573A>G	PEX3	Uncertain significance	criteria provided, single submitter
355587	NM_003630.3(PEX3):c.*677C>T	PEX3	Uncertain significance	criteria provided, single submitter
355588	NM_003630.3(PEX3):c.*793T>C	PEX3	Uncertain significance	criteria provided, single submitter
355590	NM_003630.3(PEX3):c.*958T>C	PEX3	Uncertain significance	criteria provided, single submitter
355591	NM_003630.3(PEX3):c.*1074A>G	PEX3	Uncertain significance	criteria provided, single submitter
355592	NM_003630.3(PEX3):c.*1305C>T	PEX3	Uncertain significance	criteria provided, single submitter
355593	NM_003630.3(PEX3):c.*1332A>G	PEX3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
PEX3	Definitive	Autosomal recessive	peroxisome biogenesis disorder 10A (Zellweger)	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX3	Orphanet:44	Neonatal adrenoleukodystrophy
PEX3	Orphanet:772	Infantile Refsum disease
PEX3	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
PEX3	HGNC:8858	ENSG00000034693	P56589	Peroxisomal biogenesis factor 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX3	Peroxisomal biogenesis factor 3	Involved in peroxisome biosynthesis and integrity.

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)
PEX3	Other/Unknown	no		Peroxin-3

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
adrenal tissue	1
endothelial cell	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX3	291	ubiquitous	marker	adrenal tissue, endothelial cell, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX3	1,838

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX3	P56589	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
ABC transporters in lipid homeostasis	1	601.0×	0.002	PEX3
Class I peroxisomal membrane protein import	1	519.1×	0.002	PEX3

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 membrane	1	2808.7×	7e-04	PEX3
peroxisome organization	1	802.5×	0.001	PEX3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEX3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PEX3	1	Binding:1

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	PEX3

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)
PEX3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.