peroxisome biogenesis disorder 13A (Zellweger)

Summary

peroxisome biogenesis disorder 13A (Zellweger) (MONDO:0013952) is a disease caused by PEX14 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PEX14 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 62

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 13A (Zellweger)
Mondo ID	MONDO:0013952
MeSH	C566624
OMIM	614887
DOID	DOID:0080487
UMLS	C3554004
MedGen	766918
GARD	0015877
Is cancer (heuristic)	no

Also known as: PBD13A · peroxisome biogenesis disorder 13A (Zellweger)

Data availability: 62 ClinVar variants · 4 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 PEX14 defect › peroxisome biogenesis disorder 13A (Zellweger)

Related subtypes (1): peroxisome biogenesis disorder, complementation group K

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

62 retrieved; paginated sample, class counts are floors:

25 uncertain significance, 19 conflicting classifications of pathogenicity, 8 benign, 8 benign/likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7701	NM_004565.3(PEX14):c.553C>T (p.Gln185Ter)	LOC126805616	Pathogenic	no assertion criteria provided
7702	NG_008340.2:g.(25377_66267)_(66353_129292)del	PEX14	Pathogenic	no assertion criteria provided
198515	NM_004565.3(PEX14):c.575C>G (p.Ala192Gly)	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
598254	NM_004565.3(PEX14):c.516C>T (p.Ser172=)	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876453	NM_004565.3(PEX14):c.488-14C>T	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259436	NM_004565.3(PEX14):c.36+8G>A	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286053	NM_004565.3(PEX14):c.795A>G (p.Ser265=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286703	NM_004565.3(PEX14):c.825G>A (p.Ser275=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291674	NM_004565.3(PEX14):c.297C>T (p.Tyr99=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291675	NM_004565.3(PEX14):c.381C>T (p.Tyr127=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291679	NM_004565.3(PEX14):c.855C>G (p.Gly285=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291682	NM_004565.3(PEX14):c.993T>G (p.Asp331Glu)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
501866	NM_004565.3(PEX14):c.*7G>T	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
595683	NM_004565.3(PEX14):c.416G>A (p.Arg139Gln)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
755301	NM_004565.3(PEX14):c.861G>T (p.Thr287=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
800261	NM_004565.3(PEX14):c.766G>A (p.Val256Met)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874497	NM_004565.3(PEX14):c.26A>T (p.Gln9Leu)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874499	NM_004565.3(PEX14):c.170-13C>T	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874557	NM_004565.3(PEX14):c.912C>T (p.Asp304=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874558	NM_004565.3(PEX14):c.1128G>C (p.Arg376=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
95144	NM_004565.3(PEX14):c.360A>G (p.Ala120=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357228	NM_004565.3(PEX14):c.862G>A (p.Val288Ile)	PEX14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1488796	NM_004565.3(PEX14):c.1081G>A (p.Val361Met)	PEX14	Uncertain significance	criteria provided, multiple submitters, no conflicts
167452	NM_004565.3(PEX14):c.1013A>G (p.Asp338Gly)	PEX14	Uncertain significance	criteria provided, multiple submitters, no conflicts
291673	NM_004565.3(PEX14):c.274C>G (p.Pro92Ala)	PEX14	Uncertain significance	criteria provided, multiple submitters, no conflicts
291680	NM_004565.3(PEX14):c.883C>T (p.Pro295Ser)	PEX14	Uncertain significance	criteria provided, multiple submitters, no conflicts
291681	NM_004565.3(PEX14):c.925G>T (p.Val309Leu)	PEX14	Uncertain significance	criteria provided, multiple submitters, no conflicts
291684	NM_004565.3(PEX14):c.*400G>T	PEX14	Uncertain significance	criteria provided, single submitter
291685	NM_004565.3(PEX14):c.*515C>T	PEX14	Uncertain significance	criteria provided, single submitter
291686	NM_004565.3(PEX14):c.*564C>T	PEX14	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
PEX14	Definitive	Autosomal recessive	peroxisome biogenesis disorder	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX14	Orphanet:44	Neonatal adrenoleukodystrophy
PEX14	Orphanet:772	Infantile Refsum disease
PEX14	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
PEX14	HGNC:8856	ENSG00000142655	O75381	Peroxisomal membrane protein PEX14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX14	Peroxisomal membrane protein PEX14	Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX14	Other/Unknown	no		Pex14_N, PEX14, WH-like_DNA-bd_sf

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
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX14	286	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX14	1,273

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX14	O75381	4

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	PEX14
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX14
Peroxisomal protein import	1	173.0×	0.006	PEX14

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
peroxisome transport along microtubule	1	16852.0×	7e-04	PEX14
protein import into peroxisome matrix, docking	1	4213.0×	9e-04	PEX14
protein import into peroxisome matrix, translocation	1	4213.0×	9e-04	PEX14
protein import into peroxisome matrix, substrate release	1	3370.4×	9e-04	PEX14
protein import into peroxisome matrix	1	1404.3×	0.002	PEX14
microtubule anchoring	1	1296.3×	0.002	PEX14
peroxisome organization	1	802.5×	0.002	PEX14
obsolete negative regulation of DNA-binding transcription factor activity	1	732.7×	0.002	PEX14
negative regulation of protein binding	1	624.1×	0.002	PEX14
cellular response to reactive oxygen species	1	411.0×	0.003	PEX14
protein-containing complex assembly	1	113.9×	0.010	PEX14
negative regulation of DNA-templated transcription	1	31.6×	0.032	PEX14

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEX14	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
PEX14	1	ADMET: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	1	PEX14

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)
PEX14	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.