peroxisome biogenesis disorder type 3B

Summary

peroxisome biogenesis disorder type 3B (MONDO:0009959) is a disease caused by PEX12 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PEX12 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder type 3B
Mondo ID	MONDO:0009959
OMIM	266510
DOID	DOID:0081241
UMLS	C3550693
MedGen	763607
GARD	0015226
Is cancer (heuristic)	no

Also known as: infantile phytanic acid storage disease · PBD3B · peroxisome biogenesis disorder 3B · peroxisome biogenesis disorder type 3B

Data availability: 67 ClinVar variants · 1 GenCC gene-disease record.

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 PEX12 defect › peroxisome biogenesis disorder type 3B

Related subtypes (2): peroxisome biogenesis disorder 3A (Zellweger), peroxisome biogenesis disorder, complementation group 3

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

67 retrieved; paginated sample, class counts are floors:

22 pathogenic/likely pathogenic, 17 uncertain significance, 14 likely pathogenic, 9 pathogenic, 3 conflicting classifications of pathogenicity, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1394011	NM_000286.3(PEX12):c.518G>A (p.Trp173Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191074	NM_000286.3(PEX12):c.334C>T (p.Gln112Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2034390	NM_000286.3(PEX12):c.808del (p.Gln270fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677663	NM_000286.3(PEX12):c.573_574dup (p.Leu192fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371718	NM_000286.3(PEX12):c.126+1G>T	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371737	NM_000286.3(PEX12):c.730_733dup (p.Leu245fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371738	NM_000286.3(PEX12):c.684_687del (p.Ser229fs)	PEX12	Pathogenic	criteria provided, single submitter
437449	NM_000286.3(PEX12):c.530AAC[1] (p.Gln178del)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
451464	NM_000286.3(PEX12):c.1009C>T (p.Gln337Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
501646	NM_000286.3(PEX12):c.268_271del (p.Lys90fs)	PEX12	Pathogenic	criteria provided, multiple submitters, no conflicts
550148	NM_000286.3(PEX12):c.223_224del (p.Leu75fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550907	NM_000286.3(PEX12):c.49C>T (p.Gln17Ter)	PEX12	Pathogenic	criteria provided, single submitter
551127	NM_000286.3(PEX12):c.211C>T (p.Gln71Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551557	NM_000286.3(PEX12):c.789G>A (p.Trp263Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551612	NM_000286.3(PEX12):c.460C>T (p.Arg154Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551647	NM_000286.3(PEX12):c.604C>T (p.Arg202Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
553017	NM_000286.3(PEX12):c.69_76dup (p.Gln26delinsArgTer)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
553270	NM_000286.3(PEX12):c.781del (p.Asp262fs)	PEX12	Pathogenic	criteria provided, single submitter
553650	NM_000286.3(PEX12):c.771del (p.Leu258fs)	PEX12	Pathogenic	criteria provided, single submitter
553741	NM_000286.3(PEX12):c.744dup (p.Thr249fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
554388	NM_000286.3(PEX12):c.222T>A (p.Tyr74Ter)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
555548	NM_000286.3(PEX12):c.625C>T (p.Gln209Ter)	PEX12	Pathogenic	criteria provided, multiple submitters, no conflicts
556045	NM_000286.3(PEX12):c.1044ACA[1] (p.Gln349del)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
556886	NM_000286.3(PEX12):c.644del (p.Pro215fs)	PEX12	Pathogenic	criteria provided, single submitter
557980	NM_000286.3(PEX12):c.987_988del (p.Phe330fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
558363	NM_000286.3(PEX12):c.680+1G>A	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
558619	NM_000286.3(PEX12):c.961_964del (p.Gly321fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7774	NM_000286.3(PEX12):c.538C>T (p.Arg180Ter)	PEX12	Pathogenic	criteria provided, multiple submitters, no conflicts
7775	NM_000286.3(PEX12):c.959C>T (p.Ser320Phe)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
92776	NM_000286.3(PEX12):c.888_889del (p.Leu297fs)	PEX12	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
PEX12	Definitive	Autosomal recessive	peroxisome biogenesis disorder	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX12	Orphanet:44	Neonatal adrenoleukodystrophy
PEX12	Orphanet:772	Infantile Refsum disease
PEX12	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
PEX12	HGNC:8854	ENSG00000108733	O00623	Peroxisome assembly protein 12	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX12	Peroxisome assembly protein 12	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)
PEX12	Transcription factor	no		Pex_N, Znf_RING/FYVE/PHD, PEX12

Expression context

Cohort genes with no expression data: 0.

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
choroid plexus epithelium	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX12	270	ubiquitous	yes	secondary oocyte, choroid plexus epithelium, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX12	927

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX12	O00623	81.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Class I peroxisomal membrane protein import	1	519.1×	0.006	PEX12
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX12
Peroxisomal protein import	1	173.0×	0.006	PEX12

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	PEX12
protein import into peroxisome matrix, receptor recycling	1	2407.4×	0.002	PEX12
protein targeting to peroxisome	1	1685.2×	0.002	PEX12
protein import into peroxisome matrix	1	1404.3×	0.002	PEX12
peroxisome organization	1	802.5×	0.002	PEX12
protein quality control for misfolded or incompletely synthesized proteins	1	766.0×	0.002	PEX12
cellular response to reactive oxygen species	1	411.0×	0.003	PEX12
protein monoubiquitination	1	343.9×	0.004	PEX12
protein polyubiquitination	1	115.4×	0.010	PEX12
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.019	PEX12

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
PEX12	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	PEX12

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)
PEX12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.