Rhizomelic chondrodysplasia punctata type 2

disease

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Also known as chondrodysplasia punctata, rhizomelic, due to dihydroxyacetonephosphatechondrodysplasia punctata, rhizomelic, due to Dihydroxyacetonephosphate acyltransferase deficiencyDhapat deficiencyDihydroxyacetonephosphate acyltransferase deficiencyGlyceronephosphate O-acyltransferase deficiencyGnpat deficiencyGNPAT rhizomelic chondrodysplasia punctataperoxisomal dihydroxyacetonephosphate acyltransferase deficiencyRCDP2rhizomelic chondrodysplasia punctata caused by mutation in GNPATrhizomelic chondrodysplasia punctata, type 2type 2 rhizomelic chondrodysplasia punctata

Summary

Rhizomelic chondrodysplasia punctata type 2 (MONDO:0009112) is a disease caused by GNPAT (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

Causal gene: GNPAT (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 120
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rhizomelic chondrodysplasia punctata type 2
Mondo ID	MONDO:0009112
MeSH	C537607
OMIM	222765
Orphanet	309796
DOID	DOID:0110852
ICD-11	179969811
UMLS	C1857242
MedGen	341734
GARD	0009429
Is cancer (heuristic)	no

Also known as: chondrodysplasia punctata, rhizomelic, due to dihydroxyacetonephosphate · chondrodysplasia punctata, rhizomelic, due to Dihydroxyacetonephosphate acyltransferase deficiency · Dhapat deficiency · Dihydroxyacetonephosphate acyltransferase deficiency · Glyceronephosphate O-acyltransferase deficiency · Gnpat deficiency · GNPAT rhizomelic chondrodysplasia punctata · peroxisomal dihydroxyacetonephosphate acyltransferase deficiency · RCDP2 · Rcdp2 · rhizomelic chondrodysplasia punctata caused by mutation in GNPAT · rhizomelic chondrodysplasia punctata type 2 · rhizomelic chondrodysplasia punctata, type 2 · type 2 rhizomelic chondrodysplasia punctata

Data availability: 120 ClinVar variants · 3 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 2

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

120 retrieved; paginated sample, class counts are floors:

44 uncertain significance, 27 likely pathogenic, 17 conflicting classifications of pathogenicity, 9 pathogenic, 8 benign/likely benign, 6 benign, 5 likely benign, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1252036	NM_014236.4(GNPAT):c.569-3T>G	GNPAT	Pathogenic	criteria provided, single submitter
1453740	NM_014236.4(GNPAT):c.1483del (p.Leu494_Val495insTer)	GNPAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1925833	NM_014236.4(GNPAT):c.1158G>A (p.Trp386Ter)	GNPAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675934	NM_014236.4(GNPAT):c.574del (p.Leu192fs)	GNPAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675935	NM_014236.4(GNPAT):c.180T>A (p.Tyr60Ter)	GNPAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675939	NM_014236.4(GNPAT):c.487C>T (p.Arg163Ter)	GNPAT	Pathogenic	criteria provided, multiple submitters, no conflicts
35467	NM_014236.4(GNPAT):c.1429_1430del (p.Met477fs)	GNPAT	Pathogenic	criteria provided, multiple submitters, no conflicts
35468	NM_014236.4(GNPAT):c.1937+5G>A	GNPAT	Pathogenic	no assertion criteria provided
4278055	NM_014236.4(GNPAT):c.1602+1G>A	GNPAT	Pathogenic	criteria provided, single submitter
6841	NM_014236.4(GNPAT):c.632G>A (p.Arg211His)	GNPAT	Pathogenic	criteria provided, multiple submitters, no conflicts
6843	NM_014236.4(GNPAT):c.849_850dup (p.Tyr284fs)	GNPAT	Pathogenic	criteria provided, multiple submitters, no conflicts
6844	NM_014236.4(GNPAT):c.780del (p.Asn261fs)	GNPAT	Pathogenic	no assertion criteria provided
6845	NM_014236.4(GNPAT):c.1575del (p.Phe525fs)	GNPAT	Pathogenic	criteria provided, single submitter
1324493	NM_014236.4(GNPAT):c.298C>T (p.Arg100Ter)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675927	NM_014236.4(GNPAT):c.1058dup (p.Tyr353Ter)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675928	NM_014236.4(GNPAT):c.1279+1G>T	GNPAT	Likely pathogenic	criteria provided, single submitter
2675929	NM_014236.4(GNPAT):c.1622dup (p.Tyr541Ter)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675930	NM_014236.4(GNPAT):c.807_808del (p.Glu271fs)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675931	NM_014236.4(GNPAT):c.26_27del (p.Ser9fs)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675932	NM_014236.4(GNPAT):c.913G>T (p.Glu305Ter)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675933	NM_014236.4(GNPAT):c.874_877del (p.Leu292fs)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675936	NM_014236.4(GNPAT):c.1621del (p.Tyr541fs)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675937	NM_014236.4(GNPAT):c.1718_1719del (p.Leu572_Phe573insTer)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675938	NM_014236.4(GNPAT):c.1758C>G (p.Tyr586Ter)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675940	NM_014236.4(GNPAT):c.1121del (p.Glu374fs)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675941	NM_014236.4(GNPAT):c.1297G>T (p.Glu433Ter)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675942	NM_014236.4(GNPAT):c.1482del (p.Leu494_Val495insTer)	GNPAT	Likely pathogenic	criteria provided, single submitter
2675943	NM_014236.4(GNPAT):c.1743+1G>T	GNPAT	Likely pathogenic	criteria provided, single submitter
2675944	NM_014236.4(GNPAT):c.1387del (p.Glu463fs)	GNPAT	Likely pathogenic	criteria provided, single submitter
3241714	NM_014236.4(GNPAT):c.876_877del (p.Tyr293fs)	GNPAT	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
GNPAT	Definitive	Autosomal recessive	rhizomelic chondrodysplasia punctata type 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNPAT	Orphanet:309796	Rhizomelic chondrodysplasia punctata type 2

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
GNPAT	HGNC:4416	ENSG00000116906	O15228	Dihydroxyacetone phosphate acyltransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNPAT	Dihydroxyacetone phosphate acyltransferase	Dihydroxyacetonephosphate acyltransferase catalyzing the first step in the biosynthesis of plasmalogens, a subset of phospholipids that differ from other glycerolipids by having an alkyl chain attached through a vinyl ether linkage at the…

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)
GNPAT	Enzyme (other)	yes	2.3.1.42	Plipid/glycerol_acylTrfase, GPAT/DHAPAT, DHAPAT

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
biceps brachii	1
gluteal muscle	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNPAT	294	ubiquitous	marker	gluteal muscle, biceps brachii, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNPAT	1,641

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNPAT	O15228	88.96

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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×	8e-04	GNPAT
Synthesis of PA	1	292.8×	0.005	GNPAT
Peroxisomal protein import	1	173.0×	0.006	GNPAT

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cerebellum morphogenesis	1	5617.3×	0.001	GNPAT
paranodal junction assembly	1	2808.7×	0.001	GNPAT
ether lipid biosynthetic process	1	1872.4×	0.001	GNPAT
phosphatidic acid biosynthetic process	1	510.7×	0.002	GNPAT
membrane organization	1	510.7×	0.002	GNPAT
synapse assembly	1	230.8×	0.004	GNPAT

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
GNPAT	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
GNPAT	14	Functional:8, Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GNPAT	2.3.1.42	glycerone-phosphate O-acyltransferase

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	GNPAT
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)
GNPAT	14	—

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

Cohort genes: GNPAT