peroxisome biogenesis disorder 5A (Zellweger)

Summary

peroxisome biogenesis disorder 5A (Zellweger) (MONDO:0013932) is a disease caused by PEX2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PEX2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 463

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 5A (Zellweger)
Mondo ID	MONDO:0013932
OMIM	614866
DOID	DOID:0080480
NCIT	C155756
UMLS	C3553940
MedGen	766854
GARD	0015861
Is cancer (heuristic)	no

Also known as: PBD5A · peroxisome biogenesis disorder 5A (Zellweger)

Data availability: 463 ClinVar variants · 2 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 PEX2 defect › peroxisome biogenesis disorder 5A (Zellweger)

Related subtypes (1): peroxisome biogenesis disorder 5B

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

463 retrieved; paginated sample, class counts are floors:

206 uncertain significance, 138 likely benign, 31 pathogenic, 24 pathogenic/likely pathogenic, 24 likely pathogenic, 20 benign, 17 conflicting classifications of pathogenicity, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071201	NM_000318.3(PEX2):c.115C>T (p.Gln39Ter)	PEX2	Pathogenic	criteria provided, single submitter
1072641	NM_000318.3(PEX2):c.79_80del (p.Lys27fs)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180750	NM_000318.3(PEX2):c.146del (p.Leu48_Leu49insTer)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1206131	NM_000318.3(PEX2):c.286C>T (p.Gln96Ter)	PEX2	Pathogenic	criteria provided, multiple submitters, no conflicts
1324883	NM_000318.3(PEX2):c.618del (p.Leu207fs)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1357556	NM_000318.3(PEX2):c.416_417del (p.Val139fs)	PEX2	Pathogenic	criteria provided, single submitter
13704	NM_000318.3(PEX2):c.355C>T (p.Arg119Ter)	PEX2	Pathogenic	criteria provided, multiple submitters, no conflicts
139588	NM_000318.3(PEX2):c.279_283del (p.Arg94fs)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
139589	NM_000318.3(PEX2):c.739T>C (p.Cys247Arg)	PEX2	Pathogenic	no assertion criteria provided
1402879	NM_000318.3(PEX2):c.571del (p.Tyr190_Met191insTer)	PEX2	Pathogenic	criteria provided, single submitter
1432240	NM_000318.3(PEX2):c.157G>T (p.Glu53Ter)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1434446	NM_000318.3(PEX2):c.10A>T (p.Arg4Ter)	PEX2	Pathogenic	criteria provided, single submitter
1440447	NM_000318.3(PEX2):c.386T>A (p.Leu129Ter)	PEX2	Pathogenic	criteria provided, single submitter
1442703	NM_000318.3(PEX2):c.220dup (p.Ala74fs)	PEX2	Pathogenic	criteria provided, single submitter
1445756	NM_000318.3(PEX2):c.524del (p.Ser175fs)	PEX2	Pathogenic	criteria provided, single submitter
1454128	NM_000318.3(PEX2):c.91C>T (p.Gln31Ter)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455464	NM_000318.3(PEX2):c.387_396dup (p.Gly133fs)	PEX2	Pathogenic	criteria provided, single submitter
1458316	NM_000318.3(PEX2):c.455_456insG (p.Ile152fs)	PEX2	Pathogenic	criteria provided, single submitter
1458503	NM_000318.3(PEX2):c.24_25del (p.Lys9fs)	PEX2	Pathogenic	criteria provided, single submitter
1459961	NM_000318.3(PEX2):c.550_551insC (p.Cys184fs)	PEX2	Pathogenic	criteria provided, single submitter
1698666	NM_000318.3(PEX2):c.325dup (p.Cys109fs)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1968031	NM_000318.3(PEX2):c.118del (p.Cys40fs)	PEX2	Pathogenic	criteria provided, single submitter
2019116	NM_000318.3(PEX2):c.414_426dup (p.Ile143fs)	PEX2	Pathogenic	criteria provided, single submitter
2019730	NM_000318.3(PEX2):c.15dup (p.Glu6fs)	PEX2	Pathogenic	criteria provided, single submitter
2070891	NM_000318.3(PEX2):c.39_40del (p.Arg13fs)	PEX2	Pathogenic	criteria provided, single submitter
2115889	NM_000318.3(PEX2):c.475C>T (p.Gln159Ter)	PEX2	Pathogenic	criteria provided, single submitter
2135359	NM_000318.3(PEX2):c.610_611del (p.Leu204fs)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2160134	NM_000318.3(PEX2):c.314G>A (p.Trp105Ter)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2422870	NC_000008.10:g.(?77895497)(77896414_?)del	PEX2	Pathogenic	criteria provided, single submitter
2677672	NM_000318.3(PEX2):c.183G>A (p.Trp61Ter)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
PEX2	Definitive	Autosomal recessive	peroxisome biogenesis disorder	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX2	HGNC:9717	ENSG00000164751	P28328	Peroxisome biogenesis factor 2	gencc,clinvar
LINC01978	HGNC:52806	ENSG00000262188		long intergenic non-protein coding RNA 1978	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX2	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD
LINC01978	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory segment of nasal mucosa	1
seminal vesicle	1
ventricular zone	1
C1 segment of cervical spinal cord	1
lower esophagus mucosa	1
substantia nigra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX2	291	ubiquitous	marker	seminal vesicle, ventricular zone, olfactory segment of nasal mucosa
LINC01978	124	tissue_specific	yes	C1 segment of cervical spinal cord, lower esophagus mucosa, substantia nigra

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX2	1,018
LINC01978	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX2	P28328	81.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Class I peroxisomal membrane protein import	1	519.1×	0.006	PEX2
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX2
Peroxisomal protein import	1	173.0×	0.006	PEX2

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
response to amino acid starvation	1	4213.0×	0.002	PEX2
protein import into peroxisome matrix, substrate release	1	3370.4×	0.002	PEX2
protein import into peroxisome matrix, receptor recycling	1	2407.4×	0.002	PEX2
protein import into peroxisome matrix	1	1404.3×	0.002	PEX2
pexophagy	1	1053.2×	0.002	PEX2
peroxisome organization	1	802.5×	0.002	PEX2
very long-chain fatty acid metabolic process	1	766.0×	0.002	PEX2
negative regulation of fibroblast proliferation	1	495.6×	0.003	PEX2
cellular response to reactive oxygen species	1	411.0×	0.003	PEX2
fatty acid beta-oxidation	1	374.5×	0.003	PEX2
protein monoubiquitination	1	343.9×	0.003	PEX2
protein destabilization	1	290.6×	0.003	PEX2
negative regulation of epithelial cell proliferation	1	290.6×	0.003	PEX2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEX2	0	0
LINC01978	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
PEX2	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	2	PEX2, LINC01978

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)
PEX2	1	—
LINC01978	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.