Rhizomelic chondrodysplasia punctata type 3

Summary

Rhizomelic chondrodysplasia punctata type 3 (MONDO:0010823) is a disease caused by AGPS (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: AGPS (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 204
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rhizomelic chondrodysplasia punctata type 3
Mondo ID	MONDO:0010823
MeSH	C537608
OMIM	600121
Orphanet	309803
DOID	DOID:0110853
ICD-11	110878063
UMLS	C1838612
MedGen	374012
GARD	0009682
Is cancer (heuristic)	no

Also known as: AGPS deficiency · AGPS rhizomelic chondrodysplasia punctata · alkyldihydroxyacetonephosphate synthase deficiency · alkylglycerone-phosphate synthase deficiency · RCDP3 · rhizomelic chondrodysplasia punctata caused by mutation in AGPS · rhizomelic chondrodysplasia punctata type 3 · rhizomelic chondrodysplasia punctata, type 3

Data availability: 204 ClinVar variants · 5 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 3

Related subtypes (3): rhizomelic chondrodysplasia punctata type 1, rhizomelic chondrodysplasia punctata type 2, 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

204 retrieved; paginated sample, class counts are floors:

106 uncertain significance, 28 benign, 24 likely benign, 20 likely pathogenic, 12 conflicting classifications of pathogenicity, 9 benign/likely benign, 4 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
35469	NM_003659.4(AGPS):c.1703C>T (p.Thr568Met)	AGPS	Pathogenic	no assertion criteria provided
4292356	NM_003659.4(AGPS):c.638-1G>A	AGPS	Pathogenic	criteria provided, single submitter
4292606	NM_003659.4(AGPS):c.1736dup (p.Tyr580fs)	AGPS	Pathogenic	criteria provided, single submitter
6647	NM_003659.4(AGPS):c.1406T>C (p.Leu469Pro)	AGPS	Pathogenic	no assertion criteria provided
944256	NM_003659.4(AGPS):c.544C>T (p.Arg182Ter)	AGPS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1120083	NM_003659.4(AGPS):c.1037_1043del (p.Glu346fs)	AGPS	Likely pathogenic	criteria provided, single submitter
2674880	NM_003659.4(AGPS):c.288G>A (p.Trp96Ter)	AGPS	Likely pathogenic	criteria provided, single submitter
2674887	NM_003659.4(AGPS):c.1608-1G>A	AGPS	Likely pathogenic	criteria provided, single submitter
2674897	NM_003659.4(AGPS):c.1557_1564del (p.Glu520fs)	AGPS	Likely pathogenic	criteria provided, single submitter
2674902	NM_003659.4(AGPS):c.557_562+5del	AGPS	Likely pathogenic	criteria provided, single submitter
2674911	NM_003659.4(AGPS):c.1546-84_1591dup	AGPS	Likely pathogenic	criteria provided, single submitter
2674919	NM_003659.4(AGPS):c.637+2T>A	AGPS	Likely pathogenic	criteria provided, single submitter
2674927	NM_003659.4(AGPS):c.595G>T (p.Glu199Ter)	AGPS	Likely pathogenic	criteria provided, single submitter
2674935	NM_003659.4(AGPS):c.301dup (p.Ser101fs)	AGPS	Likely pathogenic	criteria provided, single submitter
2674943	NM_003659.4(AGPS):c.562+1G>A	AGPS	Likely pathogenic	criteria provided, single submitter
2674952	NM_003659.4(AGPS):c.610C>T (p.Arg204Ter)	AGPS	Likely pathogenic	criteria provided, single submitter
2674959	NM_003659.4(AGPS):c.1536dup (p.Tyr513fs)	AGPS	Likely pathogenic	criteria provided, single submitter
2674962	NM_003659.4(AGPS):c.710-2A>G	AGPS	Likely pathogenic	criteria provided, single submitter
2674965	NM_003659.4(AGPS):c.918_919del (p.Glu306fs)	AGPS	Likely pathogenic	criteria provided, single submitter
3241201	NM_003659.4(AGPS):c.505A>T (p.Lys169Ter)	AGPS	Likely pathogenic	criteria provided, single submitter
3241205	NM_003659.4(AGPS):c.580delinsCC (p.Ile194fs)	AGPS	Likely pathogenic	criteria provided, single submitter
4815255	NM_003659.3(AGPS):c.1286delG	AGPS	Likely pathogenic	criteria provided, single submitter
4815256	NM_003659.4(AGPS):c.815del (p.Asn272fs)	AGPS	Likely pathogenic	criteria provided, single submitter
6645	NM_003659.4(AGPS):c.1256G>A (p.Arg419His)	AGPS	Likely pathogenic	criteria provided, single submitter
6646	NM_003659.4(AGPS):c.926C>T (p.Thr309Ile)	AGPS	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2075066	NM_003659.4(AGPS):c.1204G>A (p.Val402Ile)	AGPS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289429	NM_003659.4(AGPS):c.1380A>C (p.Pro460=)	AGPS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
332515	NM_003659.4(AGPS):c.637+13C>T	AGPS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
497713	NM_003659.4(AGPS):c.1335C>T (p.Asp445=)	AGPS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
747115	NM_003659.4(AGPS):c.1569A>G (p.Val523=)	AGPS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
AGPS	Definitive	Autosomal recessive	rhizomelic chondrodysplasia punctata type 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AGPS	Orphanet:309803	Rhizomelic chondrodysplasia punctata type 3

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
AGPS	HGNC:327	ENSG00000018510	O00116	Alkyldihydroxyacetonephosphate synthase, peroxisomal	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AGPS	Alkyldihydroxyacetonephosphate synthase, peroxisomal	Catalyzes the exchange of the acyl chain in acyl-dihydroxyacetonephosphate (acyl-DHAP) for a long chain fatty alcohol, yielding the first ether linked intermediate, i.e. alkyl-dihydroxyacetonephosphate (alkyl-DHAP), in the pathway of ether…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AGPS	Enzyme (other)	yes	2.5.1.26	FAD-bd_oxidored_4_C, Oxid_FAD_bind_N, FAD-linked_Oxase-like_C

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
calcaneal tendon	1
sperm	1
tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AGPS	278	ubiquitous	marker	sperm, calcaneal tendon, tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGPS	2,656

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGPS	O00116	89.27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Plasmalogen biosynthesis	1	3806.7×	9e-04	AGPS
Wax and plasmalogen biosynthesis	1	3806.7×	9e-04	AGPS
TYSND1 cleaves peroxisomal proteins	1	1427.5×	0.002	AGPS
Protein localization	1	190.3×	0.008	AGPS
Peroxisomal protein import	1	173.0×	0.008	AGPS
Metabolism of lipids	1	31.6×	0.037	AGPS
Metabolism	1	11.6×	0.086	AGPS

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×	0.001	AGPS
lipid biosynthetic process	1	991.3×	0.001	AGPS

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
AGPS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AGPS	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AGPS	2.5.1.26	alkylglycerone-phosphate synthase

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	1	AGPS
E	Difficult family or no structure, no drug	0

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)
AGPS	5	—

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