peroxisome biogenesis disorder 6B

Summary

peroxisome biogenesis disorder 6B (MONDO:0013937) is a disease caused by PEX10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PEX10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 6B
Mondo ID	MONDO:0013937
OMIM	614871
DOID	DOID:0081435
NCIT	C155759
UMLS	C3553948
MedGen	766862
GARD	0015865
Is cancer (heuristic)	no

Also known as: PBD6B · peroxisome biogenesis disorder 6B · peroxisome biogenesis disorder type 6B

Data availability: 71 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 6B

Related subtypes (1): peroxisome biogenesis disorder 6A (Zellweger)

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

71 retrieved; paginated sample, class counts are floors:

19 likely pathogenic, 18 uncertain significance, 12 pathogenic/likely pathogenic, 12 pathogenic, 6 conflicting classifications of pathogenicity, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
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
1804978	NM_002617.4(PEX10):c.637dup (p.Ala213fs)	PEX10	Pathogenic	criteria provided, single submitter
280002	NM_002617.4(PEX10):c.1A>G (p.Met1Val)	PEX10	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
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
553280	NM_002617.4(PEX10):c.600+1del	PEX10	Pathogenic	criteria provided, single submitter
554342	NM_002617.4(PEX10):c.912+1G>C	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
554630	NM_002617.4(PEX10):c.761del (p.Gly254fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
555863	NM_002617.4(PEX10):c.26del (p.Pro9fs)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
556606	NM_002617.4(PEX10):c.601-38_601-37del	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
557464	NM_002617.4(PEX10):c.692_703del (p.Ser231_Gln235delinsTer)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6770	NM_002617.4(PEX10):c.600+1G>A	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
6772	NM_002617.4(PEX10):c.373C>T (p.Arg125Ter)	PEX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6774	NM_002617.4(PEX10):c.704dup (p.Leu236fs)	PEX10	Pathogenic	criteria provided, multiple submitters, no conflicts
162432	NM_002617.4(PEX10):c.830T>C (p.Leu277Pro)	PEX10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1724122	NM_002617.4(PEX10):c.222_223del (p.Ser75fs)	PEX10	Likely pathogenic	criteria provided, single submitter
1724150	NM_002617.4(PEX10):c.135G>A (p.Trp45Ter)	PEX10	Likely pathogenic	criteria provided, single submitter
1724319	NM_002617.4(PEX10):c.618del (p.Gly208fs)	PEX10	Likely pathogenic	criteria provided, single submitter
1724832	NM_002617.4(PEX10):c.445_452del (p.Thr149fs)	PEX10	Likely pathogenic	criteria provided, single submitter
1725819	NM_002617.4(PEX10):c.522_523del (p.Gln175fs)	PEX10	Likely 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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX10	HGNC:8851	ENSG00000157911	O60683	Peroxisome biogenesis factor 10	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX10	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD

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
C1 segment of cervical spinal cord	1
parotid gland	1
tendon of biceps brachii	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX10	1,117

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX10	O60683	82.81

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
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 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 matrix, substrate release	1	3370.4×	0.002	PEX10
protein import into peroxisome matrix, receptor recycling	1	2407.4×	0.002	PEX10
protein import into peroxisome matrix	1	1404.3×	0.002	PEX10
peroxisome organization	1	802.5×	0.002	PEX10
protein quality control for misfolded or incompletely synthesized proteins	1	766.0×	0.002	PEX10
cellular response to reactive oxygen species	1	411.0×	0.003	PEX10
protein polyubiquitination	1	115.4×	0.010	PEX10
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.019	PEX10

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
PEX10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	PEX10

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)
PEX10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.