Rhizomelic chondrodysplasia punctata type 1

Summary

Rhizomelic chondrodysplasia punctata type 1 (MONDO:0008972) is a disease caused by PEX7 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: PEX7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 146
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rhizomelic chondrodysplasia punctata type 1
Mondo ID	MONDO:0008972
OMIM	215100
Orphanet	309789
DOID	DOID:0110851
ICD-11	44503513
UMLS	C1859133
MedGen	347072
GARD	0006049
Is cancer (heuristic)	no

Also known as: PBD9 · Pbd9 · peroxisome biogenesis disorder 9 · PEX7 rhizomelic chondrodysplasia punctata · RCDP1 · Rcdp1 · rhizomelic chondrodysplasia punctata caused by mutation in PEX7 · rhizomelic chondrodysplasia punctata type 1 · rhizomelic chondrodysplasia punctata, type 1

Data availability: 146 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › rhizomelic chondrodysplasia punctata › rhizomelic chondrodysplasia punctata type 1

Related subtypes (3): rhizomelic chondrodysplasia punctata type 2, rhizomelic chondrodysplasia punctata type 3, peroxisome biogenesis disorder due to PEX5 defect in the PEX7-binding domain

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

146 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 39 likely pathogenic, 21 conflicting classifications of pathogenicity, 16 pathogenic, 14 pathogenic/likely pathogenic, 6 benign, 4 benign/likely benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1338760	NM_000288.4(PEX7):c.294del (p.Ala100fs)	PEX7	Pathogenic	no assertion criteria provided
1339708	NM_000288.4(PEX7):c.376C>T (p.Gln126Ter)	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
225436	NM_000288.4(PEX7):c.183del (p.Phe61fs)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3336540	NM_000288.4(PEX7):c.283T>G (p.Trp95Gly)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
370629	NM_000288.4(PEX7):c.13_19dup (p.Gly7fs)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
370682	NM_000288.4(PEX7):c.277C>T (p.Gln93Ter)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370867	NM_000288.4(PEX7):c.508del (p.Cys170fs)	PEX7	Pathogenic	criteria provided, single submitter
371166	NM_000288.4(PEX7):c.339+2T>C	PEX7	Pathogenic	criteria provided, single submitter
371661	NM_000288.4(PEX7):c.334C>T (p.Gln112Ter)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
38872	NM_000288.4(PEX7):c.854A>G (p.His285Arg)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
436286	NM_000288.4(PEX7):c.357G>A (p.Trp119Ter)	PEX7	Pathogenic	criteria provided, single submitter
436288	NM_000288.4(PEX7):c.538del (p.Thr179_Leu180insTer)	PEX7	Pathogenic	criteria provided, single submitter
552148	NM_000288.4(PEX7):c.871_874del (p.Cys290_Gly291insTer)	PEX7	Pathogenic	criteria provided, single submitter
554785	NM_000288.4(PEX7):c.429del (p.Val144fs)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
639671	NM_000288.4(PEX7):c.130+1G>A	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
7780	NM_000288.4(PEX7):c.875T>A (p.Leu292Ter)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
7781	NM_000288.4(PEX7):c.653C>T (p.Ala218Val)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7782	NM_000288.4(PEX7):c.649G>A (p.Gly217Arg)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7783	NM_000288.4(PEX7):c.694C>T (p.Arg232Ter)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
7784	NM_000288.4(PEX7):c.45_52dup (p.His18fs)	PEX7	Pathogenic	criteria provided, single submitter
7785	NM_000288.4(PEX7):c.903+1G>C	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
7786	NM_000288.4(PEX7):c.345T>G (p.Tyr115Ter)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
7788	NM_000288.4(PEX7):c.120C>G (p.Tyr40Ter)	PEX7	Pathogenic	criteria provided, multiple submitters, no conflicts
7790	NM_000288.4(PEX7):c.40A>C (p.Thr14Pro)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813363	NM_000288.4(PEX7):c.188+1G>A	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813366	NM_000288.4(PEX7):c.592C>T (p.Gln198Ter)	PEX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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	rhizomelic chondrodysplasia punctata type 1	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

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
PEX7	HGNC:8860	ENSG00000112357	O00628	Peroxisomal targeting signal 2 receptor	gencc,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.

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
Scaffold/PPI	1	17.3×	0.058

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

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
esophagus squamous epithelium	1
pigmented layer of retina	1
sperm	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX7	1,356

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX7	O00628	95.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Peroxisomal protein import	1	173.0×	0.006	PEX7

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
ether lipid biosynthetic process	1	1872.4×	0.002	PEX7
protein targeting to peroxisome	1	1685.2×	0.002	PEX7
protein import into peroxisome matrix	1	1404.3×	0.002	PEX7
peroxisome organization	1	802.5×	0.002	PEX7
endochondral ossification	1	543.6×	0.003	PEX7
fatty acid beta-oxidation	1	374.5×	0.003	PEX7
neuron migration	1	133.8×	0.007	PEX7

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
PEX7	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	PEX7

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)
PEX7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04569162	Not specified	RECRUITING	Rhizomelic Chondrodysplasia Punctata Registry