peroxisome biogenesis disorder 9B

Summary

peroxisome biogenesis disorder 9B (MONDO:0013945) is a disease caused by PEX7 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PEX7 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 607

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder 9B
Mondo ID	MONDO:0013945
OMIM	614879
DOID	DOID:0081438
UMLS	C2749346
MedGen	440765
GARD	0015871
Is cancer (heuristic)	no

Also known as: PBD9B · peroxisome biogenesis disorder 9B · peroxisome biogenesis disorder type 9B

Data availability: 607 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 9B

Related subtypes (14): peroxisome biogenesis disorder due to PEX1 defect, peroxisome biogenesis disorder due to PEX2 defect, peroxisome biogenesis disorder due to PEX3 defect, peroxisome biogenesis disorder due to PEX5 defect, peroxisome biogenesis disorder due to PEX6 defect, peroxisome biogenesis disorder due to PEX10 defect, peroxisome biogenesis disorder due to PEX12 defect, peroxisome biogenesis disorder due to PEX13 defect, peroxisome biogenesis disorder due to PEX14 defect, peroxisome biogenesis disorder due to PEX16 defect, peroxisome biogenesis disorder due to PEX19 defect, peroxisome biogenesis disorder due to PEX26 defect, peroxisome biogenesis disorder due to PEX11B defect, peroxisome biogenesis disorder, complementation group 2

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

600 retrieved; paginated sample, class counts are floors:

289 likely benign, 148 uncertain significance, 48 pathogenic, 43 likely pathogenic, 31 conflicting classifications of pathogenicity, 20 pathogenic/likely pathogenic, 15 benign, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3246073	NC_000006.11:g.(?135606783)(138202456_?)del	AHI1	Pathogenic	criteria provided, single submitter
1068851	NM_000288.4(PEX7):c.112C>T (p.Gln38Ter)	PEX7	Pathogenic	criteria provided, single submitter
1070609	NC_000006.11:g.(?137187755)(137193401_?)del	PEX7	Pathogenic	criteria provided, single submitter
1073525	NM_000288.4(PEX7):c.860_861del (p.Glu287fs)	PEX7	Pathogenic	criteria provided, single submitter
1074641	NM_000288.4(PEX7):c.364del (p.Thr122fs)	PEX7	Pathogenic	criteria provided, single submitter
1075998	NM_000288.4(PEX7):c.474_477del (p.Tyr159fs)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339708	NM_000288.4(PEX7):c.376C>T (p.Gln126Ter)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1384934	NM_000288.4(PEX7):c.57_67dup (p.Glu23fs)	PEX7	Pathogenic	criteria provided, single submitter
1421713	NM_000288.4(PEX7):c.517del (p.Ser173fs)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1449189	NM_000288.4(PEX7):c.488G>A (p.Trp163Ter)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453098	NM_000288.4(PEX7):c.130+2T>G	PEX7	Pathogenic	criteria provided, single submitter
1454842	NC_000006.11:g.(?137143759)(137143943_?)del	PEX7	Pathogenic	criteria provided, single submitter
1455239	NM_000288.4(PEX7):c.546_547del (p.Ile182fs)	PEX7	Pathogenic	criteria provided, single submitter
1457391	NC_000006.11:g.(?137143759)(137167329_?)del	PEX7	Pathogenic	criteria provided, single submitter
1459604	NC_000006.11:g.(?137167201)(137234674_?)del	PEX7	Pathogenic	criteria provided, single submitter
1486959	NM_000288.4(PEX7):c.804-2A>C	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188711	NM_000288.4(PEX7):c.400G>A (p.Asp134Asn)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188975	NM_000288.4(PEX7):c.188+1G>C	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189076	NM_000288.4(PEX7):c.618G>A (p.Trp206Ter)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1926974	NM_000288.4(PEX7):c.858_867del (p.Glu287fs)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1996134	NM_000288.4(PEX7):c.105_117del (p.Gln38fs)	PEX7	Pathogenic	criteria provided, single submitter
2015707	NM_000288.4(PEX7):c.294_313dup (p.Gln105fs)	PEX7	Pathogenic	criteria provided, single submitter
2029049	NM_000288.4(PEX7):c.111_112del (p.Gln38fs)	PEX7	Pathogenic	criteria provided, single submitter
2033816	NM_000288.4(PEX7):c.52dup (p.His18fs)	PEX7	Pathogenic	criteria provided, single submitter
2074726	NM_000288.4(PEX7):c.652del (p.Ala218fs)	PEX7	Pathogenic	criteria provided, single submitter
2117483	NM_000288.4(PEX7):c.250dup (p.Ile84fs)	PEX7	Pathogenic	criteria provided, single submitter
2136476	NM_000288.4(PEX7):c.45_52del (p.Gly16fs)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
2180404	NM_000288.4(PEX7):c.370_396del (p.Gly124_Ser132del)	PEX7	Pathogenic	criteria provided, single submitter
225436	NM_000288.4(PEX7):c.183del (p.Phe61fs)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2422816	NC_000006.11:g.(?137143759)(137166840_?)del	PEX7	Pathogenic	criteria provided, single submitter

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
PEX7	Definitive	Autosomal recessive	peroxisome biogenesis disorder 9B	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX7	Orphanet:309789	Rhizomelic chondrodysplasia punctata type 1
PEX7	Orphanet:773	Adult Refsum disease
AHI1	Orphanet:220493	Joubert syndrome with ocular defect
AHI1	Orphanet:475	Isolated Joubert syndrome
AHI1	Orphanet:791	Retinitis pigmentosa

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
PEX7	HGNC:8860	ENSG00000112357	O00628	Peroxisomal targeting signal 2 receptor	gencc,clinvar
AHI1	HGNC:21575	ENSG00000135541	Q8N157	Jouberin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX7	Peroxisomal targeting signal 2 receptor	Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.
AHI1	Jouberin	Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Scaffold/PPI	2	17.3×	0.003

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX7	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
AHI1	Scaffold/PPI	no		SH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf

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
esophagus squamous epithelium	1
pigmented layer of retina	1
sperm	1
calcaneal tendon	1
pituitary gland	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX7	276	ubiquitous	marker	pigmented layer of retina, sperm, esophagus squamous epithelium
AHI1	276	ubiquitous	marker	pituitary gland, calcaneal tendon, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AHI1	1,681
PEX7	1,356

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AHI1	Q8N157	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX7	O00628	95.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 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	86.5×	0.024	PEX7
Anchoring of the basal body to the plasma membrane	1	56.5×	0.024	AHI1
Cilium Assembly	1	54.4×	0.024	AHI1
Organelle biogenesis and maintenance	1	33.0×	0.030	AHI1

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
ether lipid biosynthetic process	1	936.2×	0.006	PEX7
protein targeting to peroxisome	1	842.6×	0.006	PEX7
protein import into peroxisome matrix	1	702.2×	0.006	PEX7
regulation of behavior	1	702.2×	0.006	AHI1
photoreceptor cell outer segment organization	1	526.6×	0.006	AHI1
peroxisome organization	1	401.2×	0.007	PEX7
positive regulation of receptor internalization	1	351.1×	0.007	AHI1
motile cilium assembly	1	290.6×	0.007	AHI1
endochondral ossification	1	271.8×	0.007	PEX7
fatty acid beta-oxidation	1	187.2×	0.009	PEX7
cell surface receptor protein tyrosine kinase signaling pathway	1	86.9×	0.018	AHI1
neuron migration	1	66.9×	0.021	PEX7
intracellular protein localization	1	52.3×	0.025	AHI1
vesicle-mediated transport	1	48.1×	0.025	AHI1
cilium assembly	1	36.8×	0.031	AHI1
negative regulation of apoptotic process	1	17.4×	0.060	AHI1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	AHI1

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
PEX7	0	0
AHI1	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	PEX7, AHI1

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)
PEX7	0	—
AHI1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.