peroxisome biogenesis disorder 1B

Summary

peroxisome biogenesis disorder 1B (MONDO:0011101) is a disease caused by PEX1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PEX1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 213

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 1B
Mondo ID	MONDO:0011101
OMIM	601539
DOID	DOID:0081240
NCIT	C155749
UMLS	C0282527
MedGen	79470
GARD	0024772
Is cancer (heuristic)	no

Also known as: PBD1B · peroxisome biogenesis disorder 1B · peroxisome biogenesis disorder 1B (NALD/IRD) · peroxisome biogenesis disorder type 1B

Data availability: 213 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 PEX1 defect › peroxisome biogenesis disorder 1B

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

213 retrieved; paginated sample, class counts are floors:

91 likely pathogenic, 47 pathogenic/likely pathogenic, 27 pathogenic, 22 uncertain significance, 20 conflicting classifications of pathogenicity, 4 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1726581	NM_000466.3(PEX1):c.3258_3261del (p.Phe1086fs)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188729	NM_000466.3(PEX1):c.2926+1G>A	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189002	NM_000466.3(PEX1):c.2926+2T>C	GATAD1	Pathogenic	criteria provided, multiple submitters, no conflicts
203390	NM_000466.3(PEX1):c.3379dup (p.Arg1127fs)	GATAD1	Pathogenic	no assertion criteria provided
287046	NM_000466.3(PEX1):c.3303_3304dup (p.Cys1102fs)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371698	NM_000466.3(PEX1):c.3574C>T (p.Gln1192Ter)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371765	NM_000466.3(PEX1):c.3208-1G>A	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371774	NM_000466.3(PEX1):c.3455_3456del (p.Ser1152fs)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
495880	NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551650	NM_000466.3(PEX1):c.3038G>A (p.Arg1013His)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
591802	NM_000466.3(PEX1):c.3115del (p.Thr1039fs)	GATAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451521	NM_000466.3(PEX1):c.56_80del (p.Val19fs)	LOC129998796	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371688	NM_000466.3(PEX1):c.2T>G (p.Met1Arg)	LOC129998796	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371744	NM_000466.3(PEX1):c.1A>T (p.Met1Leu)	LOC129998796	Pathogenic	criteria provided, multiple submitters, no conflicts
558040	NM_000466.3(PEX1):c.5G>A (p.Trp2Ter)	LOC129998796	Pathogenic	criteria provided, multiple submitters, no conflicts
1442533	NM_000466.3(PEX1):c.538_541dup (p.Thr181fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453236	NM_000466.3(PEX1):c.3622del (p.Arg1208fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1495205	NM_000466.3(PEX1):c.357+1G>T	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1726455	NM_000466.3(PEX1):c.205C>T (p.Gln69Ter)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188851	NM_000466.3(PEX1):c.2391_2392del (p.Arg798fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
188873	NM_000466.3(PEX1):c.2383C>T (p.Arg795Ter)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188897	NM_000466.3(PEX1):c.643_647del (p.Thr215fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
188910	NM_000466.3(PEX1):c.782_783del (p.Gln261fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
188981	NM_000466.3(PEX1):c.3693_3696del (p.Gln1231fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
188984	NM_000466.3(PEX1):c.1716_1717del (p.His572fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
189043	NM_000466.3(PEX1):c.2916del (p.Gly973fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
189165	NM_000466.3(PEX1):c.1501_1502del (p.Leu501fs)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1981810	NM_000466.3(PEX1):c.1375G>T (p.Glu459Ter)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2094567	NM_000466.3(PEX1):c.2050C>T (p.Gln684Ter)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
217429	NM_000466.3(PEX1):c.1742G>C (p.Arg581Pro)	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · 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
PEX1	Definitive	Autosomal recessive	peroxisome biogenesis disorder 1A (Zellweger)	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX1	Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome
PEX1	Orphanet:44	Neonatal adrenoleukodystrophy
PEX1	Orphanet:772	Infantile Refsum disease
PEX1	Orphanet:912	Zellweger syndrome
GATAD1	Orphanet:154	Familial isolated dilated cardiomyopathy

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
PEX1	HGNC:8850	ENSG00000127980	O43933	Peroxisomal ATPase PEX1	gencc,clinvar
GATAD1	HGNC:29941	ENSG00000157259	Q8WUU5	GATA zinc finger domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX1	Peroxisomal ATPase PEX1	Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling.
GATAD1	GATA zinc finger domain-containing protein 1	Component of some chromatin complex recruited to chromatin sites methylated ‘Lys-4’ of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.228
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX1	Enzyme (other)	yes	3.6.4.7	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
GATAD1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, GATAD1

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
body of pancreas	1
calcaneal tendon	1
mucosa of stomach	1
inferior vagus X ganglion	1
left ovary	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX1	279	ubiquitous	marker	calcaneal tendon, body of pancreas, mucosa of stomach
GATAD1	287	ubiquitous	marker	left ovary, right uterine tube, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX1	2,413
GATAD1	1,065

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GATAD1	Q8WUU5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX1	O43933	67.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Peroxisomal protein import	1	173.0×	0.006	PEX1

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	PEX1
protein unfolding	1	1685.2×	0.002	PEX1
protein import into peroxisome matrix, receptor recycling	1	1203.7×	0.002	PEX1
protein targeting to peroxisome	1	842.6×	0.003	PEX1
protein import into peroxisome matrix	1	702.2×	0.003	PEX1
peroxisome organization	1	401.2×	0.004	PEX1
chromatin organization	1	49.6×	0.026	GATAD1
chromatin remodeling	1	36.5×	0.031	GATAD1
regulation of DNA-templated transcription	1	15.8×	0.062	GATAD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
PEX1	0	0
GATAD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PEX1	3.6.4.7	peroxisome-assembly ATPase

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	1	PEX1
E	Difficult family or no structure, no drug	1	GATAD1

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)
PEX1	0	—
GATAD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.