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Atlas / Disease / Cranio-osteoarthropathy

Cranio-osteoarthropathy

disease
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Also known as cranio osteoarthropathyCurrarino diseaseCurrarino idiopathic osteoarthropathyReginato-Schiapachasse syndrome

Summary

Cranio-osteoarthropathy (MONDO:0015466) is a disease with 1 cohort gene.

At a glance

  • Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
  • Cohort genes: 1
  • ClinVar variants: 1
  • Phenotypes (HPO): 14

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Cases/families30WorldwideValidated
Point prevalence<1 / 1 000 000WorldwideValidated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO IDTermFrequency
HP:0000239Large fontanellesVery frequent (80-99%)
HP:0000929Abnormal skull morphologyVery frequent (80-99%)
HP:0001070Mottled pigmentationVery frequent (80-99%)
HP:0003103Abnormal cortical bone morphologyVery frequent (80-99%)
HP:0001369ArthritisFrequent (30-79%)
HP:0001386Joint swellingFrequent (30-79%)
HP:0001387Joint stiffnessFrequent (30-79%)
HP:0002758OsteoarthritisFrequent (30-79%)
HP:0002815Abnormality of the kneeFrequent (30-79%)
HP:0002829ArthralgiaFrequent (30-79%)
HP:0002992Abnormality of tibia morphologyFrequent (30-79%)
HP:0100760Clubbing of toesFrequent (30-79%)
HP:0000964Eczematoid dermatitisOccasional (5-29%)
HP:0004097Deviation of fingerOccasional (5-29%)

Identifiers

Disease identifiers

FieldValue
Canonical namecranio-osteoarthropathy
Mondo IDMONDO:0015466
Orphanet1525
ICD-11225223076
SNOMED CT720753002
UMLSC2678439
MedGen394824
GARD0001564
Is cancer (heuristic)no

Also known as: cranio osteoarthropathy · Currarino disease · Currarino idiopathic osteoarthropathy · Reginato-Schiapachasse syndrome

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary hypertrophic osteoarthropathy › cranio-osteoarthropathy

Related subtypes (3): hypertrophic osteoarthropathy, primary, autosomal dominant, hypertrophic osteoarthropathy, primary, autosomal recessive, 2, hypertrophic osteoarthropathy, primary, autosomal recessive, 1

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
7917NM_000860.6(HPGD):c.418G>C (p.Ala140Pro)HPGDPathogeniccriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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.

GeneClassificationInheritanceDiseaseRecords
HPGDDefinitiveAutosomal recessivehypertrophic osteoarthropathy, primary, autosomal recessive, 110

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
HPGDOrphanet:1525Cranio-osteoarthropathy
HPGDOrphanet:217059Isolated nail clubbing
HPGDOrphanet:2796Pachydermoperiostosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
HPGDHGNC:5154ENSG00000164120P1542815-hydroxyprostaglandin dehydrogenase [NAD(+)]gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
HPGD15-hydroxyprostaglandin dehydrogenase [NAD(+)]Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto…

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.

FamilyGenesFoldFDR
Enzyme (other)112.0×0.083

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
HPGDEnzyme (other)yes1.1.1.141SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
adrenal tissue1
jejunal mucosa1
lower esophagus mucosa1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
HPGD244broadmarkeradrenal tissue, jejunal mucosa, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
HPGD4,071

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
HPGDP154286

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.

PathwayCohort genesFoldFDRSample cohort genes
Biosynthesis of D-series resolvins12855.0×7e-04HPGD
Biosynthesis of E-series 18(S)-resolvins12284.0×7e-04HPGD
Biosynthesis of Lipoxins (LX)11903.3×7e-04HPGD
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)1761.3×0.001HPGD

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 termCohort genesFoldFDRSample cohort genes
regulation of prostaglandin catabolic process116852.0×9e-04HPGD
ovulation14213.0×0.002HPGD
ductus arteriosus closure13370.4×0.002HPGD
thrombin-activated receptor signaling pathway12407.4×0.002HPGD
parturition11872.4×0.002HPGD
lipoxygenase pathway11532.0×0.002HPGD
prostaglandin metabolic process1842.6×0.003HPGD
positive regulation of vascular associated smooth muscle cell proliferation1432.1×0.005HPGD
negative regulation of cell cycle1290.6×0.006HPGD
female pregnancy1210.7×0.007HPGD
response to estradiol1198.3×0.007HPGD
transforming growth factor beta receptor signaling pathway1159.0×0.008HPGD
response to ethanol1146.5×0.008HPGD
kidney development1140.4×0.008HPGD
response to lipopolysaccharide1124.8×0.009HPGD
positive regulation of apoptotic process156.7×0.018HPGD

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
HPGDPHENYLBUTAZONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
HPGD2204

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PHENYLBUTAZONE4HPGD
CANDESARTAN CILEXETIL4HPGD
CHOLECALCIFEROL4HPGD
FLUORESCEIN4HPGD
OXAPROZIN4HPGD
BUMETANIDE4HPGD
SALMETEROL XINAFOATE4HPGD
DIBUCAINE4HPGD
INDIGOTINDISULFONATE4HPGD
CISPLATIN4HPGD
TETRABENAZINE4HPGD
TRIMETREXATE4HPGD
LABETALOL HYDROCHLORIDE4HPGD
PYRITHIONE ZINC4HPGD
DOXAZOSIN MESYLATE4HPGD
PRILOCAINE HYDROCHLORIDE4HPGD
TOLMETIN SODIUM4HPGD
CHLOROTRIANISENE4HPGD
TRAZODONE HYDROCHLORIDE4HPGD
DINOPROST TROMETHAMINE4HPGD
METHYSERGIDE MALEATE4HPGD
ETHOPROPAZINE HYDROCHLORIDE4HPGD
ACRISORCIN4HPGD
FLUOXETINE HYDROCHLORIDE4HPGD
LIOTHYRONINE SODIUM4HPGD
CARBIDOPA ANHYDROUS4HPGD
ETHOPROPAZINE4HPGD
ROSE BENGAL FREE ACID4HPGD
ROSIGLITAZONE4HPGD
RABEPRAZOLE4HPGD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
HPGD38Binding:33, Functional:3, ADMET:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
HPGD1.1.1.141, 1.3.1.4815-hydroxyprostaglandin dehydrogenase (NAD+), 13,14-dehydro-15-oxoprostaglandin 13-reductase

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

30 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.

CompoundMax phaseCohort target (bioactivity)
PHENYLBUTAZONE4HPGD
CANDESARTAN CILEXETIL4HPGD
CHOLECALCIFEROL4HPGD
FLUORESCEIN4HPGD
OXAPROZIN4HPGD
BUMETANIDE4HPGD
SALMETEROL XINAFOATE4HPGD
DIBUCAINE4HPGD
INDIGOTINDISULFONATE4HPGD
CISPLATIN4HPGD
TETRABENAZINE4HPGD
TRIMETREXATE4HPGD
LABETALOL HYDROCHLORIDE4HPGD
PYRITHIONE ZINC4HPGD
DOXAZOSIN MESYLATE4HPGD
PRILOCAINE HYDROCHLORIDE4HPGD
TOLMETIN SODIUM4HPGD
CHLOROTRIANISENE4HPGD
TRAZODONE HYDROCHLORIDE4HPGD
DINOPROST TROMETHAMINE4HPGD
METHYSERGIDE MALEATE4HPGD
ETHOPROPAZINE HYDROCHLORIDE4HPGD
ACRISORCIN4HPGD
FLUOXETINE HYDROCHLORIDE4HPGD
LIOTHYRONINE SODIUM4HPGD
CARBIDOPA ANHYDROUS4HPGD
ETHOPROPAZINE4HPGD
ROSE BENGAL FREE ACID4HPGD
ROSIGLITAZONE4HPGD
RABEPRAZOLE4HPGD

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1HPGD
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 70

This page pulls from 70 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd11intactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot