peroxisome biogenesis disorder 6A (Zellweger)

Summary

peroxisome biogenesis disorder 6A (Zellweger) (MONDO:0013936) is a disease caused by PEX10 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PEX10 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 172

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 6A (Zellweger)
Mondo ID	MONDO:0013936
MeSH	C566422
OMIM	614870
DOID	DOID:0080481
NCIT	C155758
UMLS	C3553947
MedGen	766861
GARD	0015864
Is cancer (heuristic)	no

Also known as: PBD6A · peroxisome biogenesis disorder 6A (Zellweger)

Data availability: 172 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 PEX10 defect › peroxisome biogenesis disorder 6A (Zellweger)

Related subtypes (1): peroxisome biogenesis disorder 6B

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

172 retrieved; paginated sample, class counts are floors:

58 uncertain significance, 33 likely pathogenic, 28 pathogenic/likely pathogenic, 21 conflicting classifications of pathogenicity, 14 pathogenic, 10 benign, 7 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027530	NM_002617.4(PEX10):c.496del (p.Val166fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070709	NM_002617.4(PEX10):c.703C>T (p.Gln235Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074695	NM_002617.4(PEX10):c.157_158del (p.Ser53fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1360138	NM_002617.4(PEX10):c.219C>G (p.Tyr73Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362935	NM_002617.4(PEX10):c.401_416dup (p.Gly140fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455143	NM_002617.4(PEX10):c.26dup (p.Glu10fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162431	NM_002617.4(PEX10):c.337del (p.Leu113fs)	PEX10	Pathogenic	criteria provided, single submitter
162434	NM_002617.4(PEX10):c.2T>C (p.Met1Thr)	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
162435	NM_002617.4(PEX10):c.730C>T (p.Arg244Ter)	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
1686018	NM_002617.4(PEX10):c.827G>C (p.Cys276Ser)	PEX10	Pathogenic	criteria provided, single submitter
1723948	NM_002617.4(PEX10):c.542G>A (p.Trp181Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804862	NM_002617.4(PEX10):c.13_28delinsCCGCCAGCACCTGCGCCGCC (p.Ala5fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
235465	NM_002617.4(PEX10):c.338del (p.Leu113fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677649	NM_002617.4(PEX10):c.881G>A (p.Trp294Ter)	PEX10	Pathogenic	criteria provided, single submitter
2677650	NM_002617.4(PEX10):c.408_423dup (p.Arg142fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677653	NM_002617.4(PEX10):c.346_363delinsTGGGCCCCTG (p.Glu116fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677655	NM_002617.4(PEX10):c.8del (p.Pro3fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677660	NM_002617.4(PEX10):c.746G>A (p.Trp249Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280002	NM_002617.4(PEX10):c.1A>G (p.Met1Val)	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
282334	NM_002617.4(PEX10):c.835G>T (p.Glu279Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2869078	NM_002617.4(PEX10):c.363del (p.Asp122fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2893573	NM_002617.4(PEX10):c.858_870del (p.Pro287fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
296273	NM_002617.4(PEX10):c.814_815del (p.Leu272fs)	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
3240081	NM_002617.4(PEX10):c.882G>A (p.Trp294Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3336181	NM_002617.4(PEX10):c.3G>C (p.Met1Ile)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382522	NM_002617.4(PEX10):c.209G>A (p.Gly70Glu)	PEX10	Pathogenic	criteria provided, single submitter
371748	NM_002617.4(PEX10):c.352C>T (p.Gln118Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449304	NM_002617.4(PEX10):c.4del (p.Ala2fs)	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
550383	NM_002617.4(PEX10):c.755_756del (p.His252fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
553074	NM_002617.4(PEX10):c.795_796del (p.Arg265fs)	PEX10	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
PEX10	Definitive	Autosomal recessive	peroxisome biogenesis disorder	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX10	Orphanet:247815	Autosomal recessive ataxia due to PEX10 deficiency
PEX10	Orphanet:44	Neonatal adrenoleukodystrophy
PEX10	Orphanet:772	Infantile Refsum disease
PEX10	Orphanet:912	Zellweger syndrome

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
PEX10	HGNC:8851	ENSG00000157911	O60683	Peroxisome biogenesis factor 10	gencc,clinvar
RER1	HGNC:30309	ENSG00000157916	O15258	Protein RER1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX10	Peroxisome biogenesis factor 10	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.
RER1	Protein RER1	Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment.

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)
PEX10	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD
RER1	Other/Unknown	no		Rer1

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
C1 segment of cervical spinal cord	1
parotid gland	1
tendon of biceps brachii	1
left adrenal gland	1
lower esophagus mucosa	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX10	266	ubiquitous	marker	parotid gland, tendon of biceps brachii, C1 segment of cervical spinal cord
RER1	294	ubiquitous	marker	lower esophagus mucosa, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RER1	1,787
PEX10	1,117

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX10	O60683	82.81
RER1	O15258	79.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX10
Peroxisomal protein import	1	173.0×	0.006	PEX10

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
protein import into peroxisome matrix, substrate release	1	1685.2×	0.003	PEX10
protein retention in ER lumen	1	1203.7×	0.003	RER1
protein import into peroxisome matrix, receptor recycling	1	1203.7×	0.003	PEX10
skeletal muscle acetylcholine-gated channel clustering	1	936.2×	0.003	RER1
protein import into peroxisome matrix	1	702.2×	0.003	PEX10
peroxisome organization	1	401.2×	0.004	PEX10
protein quality control for misfolded or incompletely synthesized proteins	1	383.0×	0.004	PEX10
cellular response to reactive oxygen species	1	205.5×	0.007	PEX10
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	168.5×	0.008	RER1
positive regulation of protein localization to plasma membrane	1	135.9×	0.009	RER1
protein polyubiquitination	1	57.7×	0.019	PEX10
proteasome-mediated ubiquitin-dependent protein catabolic process	1	26.1×	0.038	PEX10

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
PEX10	0	0
RER1	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
RER1	1	Binding:1

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	0
E	Difficult family or no structure, no drug	2	PEX10, RER1

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)
PEX10	0	—
RER1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.