peroxisome biogenesis disorder 11A (Zellweger)

Summary

peroxisome biogenesis disorder 11A (Zellweger) (MONDO:0013949) is a disease caused by PEX13 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: PEX13 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 550

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 11A (Zellweger)
Mondo ID	MONDO:0013949
OMIM	614883
DOID	DOID:0080485
UMLS	C3554000
MedGen	766914
GARD	0015874
Is cancer (heuristic)	no

Also known as: PBD11A · peroxisome biogenesis disorder 11A (Zellweger)

Data availability: 550 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 PEX13 defect › peroxisome biogenesis disorder 11A (Zellweger)

Related subtypes (1): peroxisome biogenesis disorder 11B

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

550 retrieved; paginated sample, class counts are floors:

289 uncertain significance, 182 likely benign, 32 pathogenic, 25 conflicting classifications of pathogenicity, 10 benign, 7 likely pathogenic, 4 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30226	NC_000002.12:g.60947640_61094952del	LOC129933826	Pathogenic	no assertion criteria provided
1372243	NM_002618.4(PEX13):c.46C>T (p.Arg16Ter)	PEX13	Pathogenic	criteria provided, single submitter
1387888	NM_002618.4(PEX13):c.499del (p.His167fs)	PEX13	Pathogenic	criteria provided, single submitter
1411346	NM_002618.4(PEX13):c.367G>T (p.Glu123Ter)	PEX13	Pathogenic	criteria provided, multiple submitters, no conflicts
1426245	NM_002618.4(PEX13):c.201dup (p.Val68fs)	PEX13	Pathogenic	criteria provided, single submitter
1428939	NM_002618.4(PEX13):c.829dup (p.Ala277fs)	PEX13	Pathogenic	criteria provided, single submitter
1453426	NM_002618.4(PEX13):c.159_160del (p.Pro54fs)	PEX13	Pathogenic	criteria provided, single submitter
1705035	NM_002618.4(PEX13):c.391C>T (p.Gln131Ter)	PEX13	Pathogenic	criteria provided, multiple submitters, no conflicts
1897669	NM_002618.4(PEX13):c.913+1G>T	PEX13	Pathogenic	criteria provided, single submitter
1993651	NM_002618.4(PEX13):c.148del (p.Arg50fs)	PEX13	Pathogenic	criteria provided, single submitter
2031148	NM_002618.4(PEX13):c.633G>A (p.Trp211Ter)	PEX13	Pathogenic	criteria provided, single submitter
2109668	NM_002618.4(PEX13):c.759_760del (p.Leu254fs)	PEX13	Pathogenic	criteria provided, single submitter
2722852	NM_002618.4(PEX13):c.744C>G (p.Tyr248Ter)	PEX13	Pathogenic	criteria provided, single submitter
2727059	NM_002618.4(PEX13):c.676C>T (p.Arg226Ter)	PEX13	Pathogenic	criteria provided, single submitter
2742993	NM_002618.4(PEX13):c.855del (p.Val286fs)	PEX13	Pathogenic	criteria provided, single submitter
2754296	NM_002618.4(PEX13):c.27del (p.Lys10fs)	PEX13	Pathogenic	criteria provided, single submitter
2757683	NM_002618.4(PEX13):c.431del (p.Ser144fs)	PEX13	Pathogenic	criteria provided, single submitter
2762794	NM_002618.4(PEX13):c.596T>G (p.Leu199Ter)	PEX13	Pathogenic	criteria provided, single submitter
2805185	NM_002618.4(PEX13):c.20dup (p.Pro8fs)	PEX13	Pathogenic	criteria provided, single submitter
2834166	NM_002618.4(PEX13):c.801G>A (p.Trp267Ter)	PEX13	Pathogenic	criteria provided, single submitter
2834722	NM_002618.4(PEX13):c.145dup (p.Thr49fs)	PEX13	Pathogenic	criteria provided, single submitter
2859713	NM_002618.4(PEX13):c.871del (p.Ile291fs)	PEX13	Pathogenic	criteria provided, single submitter
3649968	NM_002618.4(PEX13):c.213del (p.Phe71fs)	PEX13	Pathogenic	criteria provided, single submitter
3651137	NM_002618.4(PEX13):c.294T>G (p.Tyr98Ter)	PEX13	Pathogenic	criteria provided, single submitter
3673489	NM_002618.4(PEX13):c.107del (p.Gly36fs)	PEX13	Pathogenic	criteria provided, single submitter
4722094	NM_002618.4(PEX13):c.544_545insAAT (p.Phe182Ter)	PEX13	Pathogenic	criteria provided, single submitter
4733096	NM_002618.4(PEX13):c.592del (p.Met198fs)	PEX13	Pathogenic	criteria provided, single submitter
573201	NM_002618.4(PEX13):c.586C>T (p.Gln196Ter)	PEX13	Pathogenic	criteria provided, single submitter
575270	NM_002618.4(PEX13):c.508C>T (p.Arg170Ter)	PEX13	Pathogenic	criteria provided, multiple submitters, no conflicts
582828	NM_002618.4(PEX13):c.465T>G (p.Tyr155Ter)	PEX13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PEX13	Definitive	Autosomal recessive	peroxisome biogenesis disorder 11A (Zellweger)	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX13	Orphanet:44	Neonatal adrenoleukodystrophy
PEX13	Orphanet:772	Infantile Refsum disease
PEX13	Orphanet:912	Zellweger syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX13	HGNC:8855	ENSG00000162928	Q92968	Peroxisomal membrane protein PEX13	gencc,clinvar
PUS10	HGNC:26505	ENSG00000162927	Q3MIT2	tRNA pseudouridine synthase Pus10	clinvar
C2orf74	HGNC:34439	ENSG00000237651	A8MZ97	Uncharacterized protein C2orf74	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
PUS10	tRNA pseudouridine synthase Pus10	Protein with different functions depending on its subcellular location: involved in miRNA processing in the nucleus and acts as a tRNA pseudouridylate synthase in the cytoplasm.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Scaffold/PPI	1	5.8×	0.345
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX13	Scaffold/PPI	no		SH3_domain, Peroxin-13_N, Pex13
PUS10	Enzyme (other)	yes	5.4.99.25	PsdUridine_synth_cat_dom_sf, Pus10-like, Pus10-like_C
C2orf74	Other/Unknown	no		DUF4642

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
sperm	1
jejunal mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
amygdala	1
hypothalamus	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX13	264	ubiquitous	marker	secondary oocyte, sperm, oocyte
PUS10	196	ubiquitous	marker	jejunal mucosa, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
C2orf74	134	ubiquitous	marker	nucleus accumbens, amygdala, hypothalamus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX13	1,127
PUS10	807
C2orf74	161

Intra-cohort edges

A	B	Sources
C2orf74	PUS10	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX13	Q92968	3
PUS10	Q3MIT2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C2orf74	A8MZ97	58.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 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	PEX13
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX13
Peroxisomal protein import	1	173.0×	0.006	PEX13

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	PEX13
protein import into peroxisome matrix, docking	1	2106.5×	0.002	PEX13
protein import into peroxisome matrix, translocation	1	2106.5×	0.002	PEX13
tRNA pseudouridine synthesis	1	1404.3×	0.002	PUS10
fatty acid alpha-oxidation	1	1203.7×	0.002	PEX13
suckling behavior	1	842.6×	0.002	PEX13
cerebral cortex cell migration	1	766.0×	0.002	PEX13
primary miRNA processing	1	648.1×	0.002	PUS10
cellular response to reactive oxygen species	1	205.5×	0.006	PEX13
locomotory behavior	1	89.6×	0.012	PEX13
neuron migration	1	66.9×	0.015	PEX13

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
PEX13	0	0
PUS10	0	0
C2orf74	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PUS10	5.4.99.25, 5.4.99.B22, 5.4.99.B25	tRNA pseudouridine55 synthase, ,

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	PUS10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PEX13, C2orf74

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PEX13	0	—
PUS10	0	—
C2orf74	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.