peroxisome biogenesis disorder 7B

Summary

peroxisome biogenesis disorder 7B (MONDO:0013939) is a disease caused by PEX26 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PEX26 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 456

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 7B
Mondo ID	MONDO:0013939
OMIM	614873
DOID	DOID:0081436
NCIT	C155761
UMLS	C3553951
MedGen	766865
GARD	0015867
Is cancer (heuristic)	no

Also known as: PBD7B · peroxisome biogenesis disorder 7B · peroxisome biogenesis disorder type 7B

Data availability: 456 ClinVar variants · 2 GenCC gene-disease records · 6 cell lines.

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 PEX26 defect › peroxisome biogenesis disorder 7B

Related subtypes (1): peroxisome biogenesis disorder 7A (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

456 retrieved; paginated sample, class counts are floors:

190 likely benign, 177 uncertain significance, 37 conflicting classifications of pathogenicity, 29 pathogenic, 10 likely pathogenic, 8 pathogenic/likely pathogenic, 3 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2156	NM_001127649.3(PEX26):c.2T>C (p.Met1Thr)	LOC130066940	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677683	NM_001127649.3(PEX26):c.27_58dup (p.Arg20fs)	LOC130066940	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3759598	NM_001127649.3(PEX26):c.3G>A (p.Met1Ile)	LOC130066940	Pathogenic	criteria provided, multiple submitters, no conflicts
1323438	NM_001127649.3(PEX26):c.613del (p.Gln205fs)	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
1450403	NC_000022.10:g.(?18561143)(18613903_?)del	PEX26	Pathogenic	criteria provided, single submitter
1456609	NC_000022.10:g.(?18561143)(18568044_?)del	PEX26	Pathogenic	criteria provided, single submitter
1514085	NM_001127649.3(PEX26):c.667+2T>C	PEX26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1981287	NM_001127649.3(PEX26):c.329_330del (p.Tyr110fs)	PEX26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1995469	NM_001127649.3(PEX26):c.154del (p.Arg52fs)	PEX26	Pathogenic	criteria provided, single submitter
2006097	NM_001127649.3(PEX26):c.443del (p.Pro148fs)	PEX26	Pathogenic	criteria provided, single submitter
2118941	NM_001127649.3(PEX26):c.757A>T (p.Lys253Ter)	PEX26	Pathogenic	criteria provided, single submitter
2122801	NM_001127649.3(PEX26):c.725_726del (p.Ser242fs)	PEX26	Pathogenic	criteria provided, single submitter
2152	NM_001127649.3(PEX26):c.292C>T (p.Arg98Trp)	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
2153	NM_001127649.3(PEX26):c.265G>A (p.Gly89Arg)	PEX26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2154	NM_001127649.3(PEX26):c.34dup (p.Leu12fs)	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
2158	NM_001127649.3(PEX26):c.254dup (p.Cys86fs)	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
2159	NM_001127649.3(PEX26):c.230+1G>T	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
2677687	NM_001127649.3(PEX26):c.436C>T (p.Gln146Ter)	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
2921344	NM_001127649.3(PEX26):c.28del (p.Ala10fs)	PEX26	Pathogenic	criteria provided, single submitter
2925654	NM_001127649.3(PEX26):c.37_38del (p.Arg13fs)	PEX26	Pathogenic	criteria provided, single submitter
2925655	NM_001127649.3(PEX26):c.73_79del (p.Val25fs)	PEX26	Pathogenic	criteria provided, single submitter
2927899	NM_001127649.3(PEX26):c.354dup (p.Lys119fs)	PEX26	Pathogenic	criteria provided, single submitter
2928098	NM_001127649.3(PEX26):c.190_191del (p.Leu65fs)	PEX26	Pathogenic	criteria provided, multiple submitters, no conflicts
2940082	NM_001127649.3(PEX26):c.298C>T (p.Gln100Ter)	PEX26	Pathogenic	criteria provided, single submitter
2942557	NM_001127649.3(PEX26):c.297G>A (p.Trp99Ter)	PEX26	Pathogenic	criteria provided, single submitter
2942734	NM_001127649.3(PEX26):c.396del (p.Glu133fs)	PEX26	Pathogenic	criteria provided, single submitter
2943328	NM_001127649.3(PEX26):c.468T>G (p.Tyr156Ter)	PEX26	Pathogenic	criteria provided, single submitter
2954498	NM_001127649.3(PEX26):c.344del (p.Lys115fs)	PEX26	Pathogenic	criteria provided, single submitter
3750992	NM_001127649.3(PEX26):c.297dup (p.Gln100fs)	PEX26	Pathogenic	criteria provided, single submitter
3754409	NM_001127649.3(PEX26):c.575dup (p.Leu193fs)	PEX26	Pathogenic	criteria provided, single submitter

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
PEX26	Definitive	Autosomal recessive	peroxisome biogenesis disorder	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX26	Orphanet:44	Neonatal adrenoleukodystrophy
PEX26	Orphanet:772	Infantile Refsum disease
PEX26	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
PEX26	HGNC:22965	ENSG00000215193	Q7Z412	Peroxisome assembly protein 26	gencc,clinvar
MICAL3	HGNC:24694	ENSG00000243156	Q7RTP6	[F-actin]-monooxygenase MICAL3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX26	Peroxisome assembly protein 26	Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes.
MICAL3	[F-actin]-monooxygenase MICAL3	Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization.

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)
PEX26	Other/Unknown	no		Pex26
MICAL3	Transcription factor	no		CH_dom, Znf_LIM, FAD-bd

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
cortical plate	1
mucosa of transverse colon	1
tendon of biceps brachii	1
right hemisphere of cerebellum	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX26	253	ubiquitous	marker	mucosa of transverse colon, tendon of biceps brachii, cortical plate
MICAL3	197	ubiquitous	marker	sural nerve, right uterine tube, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MICAL3	1,163
PEX26	775

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MICAL3	Q7RTP6	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX26	Q7Z412	79.87

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
Class I peroxisomal membrane protein import	1	519.1×	0.004	PEX26
Peroxisomal protein import	1	173.0×	0.006	PEX26

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 to membrane docking	1	1685.2×	0.002	PEX26
protein import into peroxisome membrane	1	1404.3×	0.002	PEX26
protein import into peroxisome matrix	1	702.2×	0.003	PEX26
actin filament depolymerization	1	648.1×	0.003	MICAL3
exocytosis	1	75.9×	0.018	MICAL3
cytoskeleton organization	1	66.3×	0.018	MICAL3
cell division	1	23.1×	0.043	MICAL3

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
PEX26	0	0
MICAL3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	PEX26, MICAL3

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)
PEX26	0	—
MICAL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.