chondrodysplasia with joint dislocations, gPAPP type

Summary

chondrodysplasia with joint dislocations, gPAPP type (MONDO:0013561) is a disease caused by BPNT2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: BPNT2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 167

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	chondrodysplasia with joint dislocations, gPAPP type
Mondo ID	MONDO:0013561
OMIM	614078
Orphanet	280586
DOID	DOID:0112224
UMLS	C3279757
MedGen	481387
GARD	0011009
Is cancer (heuristic)	no

Also known as: chondrodysplasia with joint dislocations, gPAPP type · gPAPP deficiency

Data availability: 167 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › chondrodysplasia with joint dislocations, gPAPP type

Related subtypes (12): iron metabolism disease, phosphorus metabolism disease, potassium deficiency disease, calcium metabolic disease, spondyloepiphyseal dysplasia with congenital joint dislocations, diastrophic dysplasia, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, achondrogenesis type IB, spondyloepimetaphyseal dysplasia, PAPSS2 type, acquired mineral metabolism disease, sulfur metabolism disease

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

167 retrieved; paginated sample, class counts are floors:

116 uncertain significance, 23 benign, 15 likely benign, 5 pathogenic, 4 conflicting classifications of pathogenicity, 2 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162256	NM_017813.5(BPNT2):c.473_474dup (p.Thr159Ter)	BPNT2	Pathogenic	criteria provided, single submitter
162436	NM_017813.5(BPNT2):c.324del (p.Ser108fs)	BPNT2	Pathogenic	no assertion criteria provided
31090	NM_017813.5(BPNT2):c.529G>A (p.Asp177Asn)	BPNT2	Pathogenic	no assertion criteria provided
31091	NM_017813.5(BPNT2):c.547A>C (p.Thr183Pro)	BPNT2	Pathogenic	no assertion criteria provided
31092	NM_017813.5(BPNT2):c.559C>T (p.Arg187Ter)	BPNT2	Pathogenic	criteria provided, multiple submitters, no conflicts
3064488	NM_017813.5(BPNT2):c.713_714insCTTCCTATGG (p.Arg238fs)	BPNT2	Likely pathogenic	criteria provided, single submitter
3068283	NM_017813.5(BPNT2):c.1007T>C (p.Leu336Pro)	BPNT2	Likely pathogenic	criteria provided, single submitter
1905819	NM_017813.5(BPNT2):c.939del (p.His314fs)	BPNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
363409	NM_017813.5(BPNT2):c.336G>A (p.Leu112=)	BPNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909435	NM_017813.5(BPNT2):c.1041C>T (p.Val347=)	BPNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909436	NM_017813.5(BPNT2):c.987C>T (p.Asp329=)	BPNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705420	NM_017813.5(BPNT2):c.230_250dup (p.Arg83_Val84insGlyGlyAspGluValArgArg)	BPNT2	Uncertain significance	criteria provided, single submitter
3065170	NM_017813.5(BPNT2):c.1001G>A (p.Gly334Glu)	BPNT2	Uncertain significance	criteria provided, single submitter
363320	NM_017813.5(BPNT2):c.*5821C>T	BPNT2	Uncertain significance	criteria provided, single submitter
363321	NM_017813.5(BPNT2):c.*5804G>A	BPNT2	Uncertain significance	criteria provided, single submitter
363322	NM_017813.5(BPNT2):c.*5752G>A	BPNT2	Uncertain significance	criteria provided, single submitter
363329	NM_017813.5(BPNT2):c.*5463G>C	BPNT2	Uncertain significance	criteria provided, single submitter
363330	NM_017813.5(BPNT2):c.*5395A>G	BPNT2	Uncertain significance	criteria provided, single submitter
363331	NM_017813.5(BPNT2):c.*5327C>G	BPNT2	Uncertain significance	criteria provided, single submitter
363333	NM_017813.5(BPNT2):c.*5300G>T	BPNT2	Uncertain significance	criteria provided, single submitter
363334	NM_017813.5(BPNT2):c.*5203A>T	BPNT2	Uncertain significance	criteria provided, single submitter
363335	NM_017813.5(BPNT2):c.*5193A>G	BPNT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
363340	NM_017813.5(BPNT2):c.*4845A>G	BPNT2	Uncertain significance	criteria provided, single submitter
363341	NM_017813.5(BPNT2):c.*4496C>T	BPNT2	Uncertain significance	criteria provided, single submitter
363343	NM_017813.5(BPNT2):c.*4264G>A	BPNT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
363346	NM_017813.5(BPNT2):c.*3876T>A	BPNT2	Uncertain significance	criteria provided, single submitter
363348	NM_017813.5(BPNT2):c.*3739C>T	BPNT2	Uncertain significance	criteria provided, single submitter
363350	NM_017813.5(BPNT2):c.*3653C>A	BPNT2	Uncertain significance	criteria provided, single submitter
363351	NM_017813.5(BPNT2):c.*3258T>G	BPNT2	Uncertain significance	criteria provided, single submitter
363352	NM_017813.5(BPNT2):c.*3235A>C	BPNT2	Uncertain significance	criteria provided, single submitter

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
BPNT2	Definitive	Autosomal recessive	chondrodysplasia with joint dislocations, gPAPP type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BPNT2	Orphanet:280586	Chondrodysplasia with joint dislocations, gPAPP type

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
BPNT2	HGNC:26019	ENSG00000104331	Q9NX62	Golgi-resident adenosine 3’,5’-bisphosphate 3’-phosphatase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BPNT2	Golgi-resident adenosine 3’,5’-bisphosphate 3’-phosphatase	Exhibits 3’-nucleotidase activity toward adenosine 3’,5’-bisphosphate (PAP), namely hydrolyzes adenosine 3’,5’-bisphosphate into adenosine 5’-monophosphate (AMP) and a phosphate.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BPNT2	Phosphatase	yes		Inositol_monophosphatase-like, Inositol_monophosphatase_CS, CysQ/Inositol_MonoPase

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
adrenal tissue	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BPNT2	287	ubiquitous	marker	medial globus pallidus, globus pallidus, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BPNT2	1,321

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BPNT2	Q9NX62	88.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cytosolic sulfonation of small molecules	1	519.1×	0.007	BPNT2
Phase II - Conjugation of compounds	1	278.5×	0.007	BPNT2
Biological oxidations	1	129.8×	0.010	BPNT2
Metabolism	1	11.6×	0.086	BPNT2

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
chondroitin sulfate proteoglycan metabolic process	1	4213.0×	0.002	BPNT2
chondrocyte development	1	936.2×	0.004	BPNT2
endochondral ossification	1	543.6×	0.004	BPNT2
phosphatidylinositol phosphate biosynthetic process	1	481.5×	0.004	BPNT2
embryonic digit morphogenesis	1	300.9×	0.005	BPNT2
post-embryonic development	1	205.5×	0.006	BPNT2
skeletal system development	1	125.8×	0.008	BPNT2

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
BPNT2	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	1	BPNT2
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)
BPNT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.