Hypertrophic osteoarthropathy, primary, autosomal recessive, 1

Summary

Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (MONDO:0024546) is a disease caused by HPGD (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: HPGD (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 77

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic osteoarthropathy, primary, autosomal recessive, 1
Mondo ID	MONDO:0024546
OMIM	259100
UMLS	C4551679
MedGen	1641972
GARD	0015216
Is cancer (heuristic)	no

Also known as: HPGD primary hypertrophic osteoarthropathy · hypertrophic osteoarthropathy, primary, autosomal recessive 1 · hypertrophic osteoarthropathy, primary, autosomal recessive, 1 · PHOAR1 · primary hypertrophic osteoarthropathy caused by mutation in HPGD

Data availability: 77 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary hypertrophic osteoarthropathy › hypertrophic osteoarthropathy, primary, autosomal recessive, 1

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

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

77 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 14 pathogenic, 10 benign, 8 likely benign, 4 conflicting classifications of pathogenicity, 3 benign/likely benign, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
156026	NM_000860.6(HPGD):c.1A>T (p.Met1Leu)	HPGD	Pathogenic	criteria provided, single submitter
156027	NM_000860.6(HPGD):c.310_311del (p.Leu104fs)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
1708173	NM_000860.6(HPGD):c.498+1G>A	HPGD	Pathogenic	no assertion criteria provided
2203595	NM_000860.6(HPGD):c.120del (p.Ala41fs)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
2499675	NM_000860.6(HPGD):c.662+2T>A	HPGD	Pathogenic	criteria provided, single submitter
3362780	NM_000860.6(HPGD):c.324+5G>A	HPGD	Pathogenic	criteria provided, single submitter
3377527	NM_000860.6(HPGD):c.189C>A (p.Cys63Ter)	HPGD	Pathogenic	no assertion criteria provided
3691622	NM_000860.6(HPGD):c.202C>T (p.Gln68Ter)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
3718029	NM_000860.6(HPGD):c.421+1G>T	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
7917	NM_000860.6(HPGD):c.418G>C (p.Ala140Pro)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
7918	NM_000860.6(HPGD):c.232_241delinsCA (p.Val78fs)	HPGD	Pathogenic	no assertion criteria provided
7919	NM_000860.6(HPGD):c.175_176del (p.Leu59fs)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
973741	NM_000860.6(HPGD):c.34G>A (p.Gly12Ser)	HPGD	Pathogenic	no assertion criteria provided
973742	NM_000860.6(HPGD):c.313C>T (p.Gln105Ter)	HPGD	Pathogenic	criteria provided, single submitter
2440745	NM_000860.6(HPGD):c.307del (p.Thr103fs)	HPGD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3891348	NM_000860.6(HPGD):c.453T>G (p.Tyr151Ter)	HPGD	Likely pathogenic	criteria provided, single submitter
599096	NM_000860.6(HPGD):c.446C>G (p.Pro149Arg)	HPGD	Likely pathogenic	no assertion criteria provided
2058441	NM_000860.6(HPGD):c.38C>A (p.Ala13Glu)	HPGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348205	NM_000860.6(HPGD):c.78G>A (p.Leu26=)	HPGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
796877	NM_000860.6(HPGD):c.606A>G (p.Gln202=)	HPGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
899919	NM_000860.6(HPGD):c.*41A>G	HPGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1399281	NM_000860.6(HPGD):c.284A>G (p.Asn95Ser)	HPGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
1408124	NM_000860.6(HPGD):c.662+5_662+8del	HPGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2572459	NM_000860.6(HPGD):c.341G>A (p.Gly114Glu)	HPGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
289387	NM_000860.6(HPGD):c.433G>A (p.Val145Ile)	HPGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
348171	NM_000860.6(HPGD):c.*1618A>T	HPGD	Uncertain significance	criteria provided, single submitter
348172	NM_000860.6(HPGD):c.*1584A>G	HPGD	Uncertain significance	criteria provided, single submitter
348173	NM_000860.6(HPGD):c.*1556C>T	HPGD	Uncertain significance	criteria provided, single submitter
348176	NM_000860.6(HPGD):c.*1478C>T	HPGD	Uncertain significance	criteria provided, single submitter
348177	NM_000860.6(HPGD):c.*1400T>G	HPGD	Uncertain significance	criteria provided, single submitter

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.

Gene	Classification	Inheritance	Disease	Records
HPGD	Definitive	Autosomal recessive	hypertrophic osteoarthropathy, primary, autosomal recessive, 1	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HPGD	Orphanet:1525	Cranio-osteoarthropathy
HPGD	Orphanet:217059	Isolated nail clubbing
HPGD	Orphanet:2796	Pachydermoperiostosis

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
HPGD	HGNC:5154	ENSG00000164120	P15428	15-hydroxyprostaglandin dehydrogenase [NAD(+)]	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HPGD	15-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.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HPGD	Enzyme (other)	yes	1.1.1.141	SDR_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)

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
jejunal mucosa	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HPGD	244	broad	marker	adrenal tissue, jejunal mucosa, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPGD	4,071

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HPGD	P15428	6

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
Biosynthesis of D-series resolvins	1	2855.0×	7e-04	HPGD
Biosynthesis of E-series 18(S)-resolvins	1	2284.0×	7e-04	HPGD
Biosynthesis of Lipoxins (LX)	1	1903.3×	7e-04	HPGD
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	1	761.3×	0.001	HPGD

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
regulation of prostaglandin catabolic process	1	16852.0×	9e-04	HPGD
ovulation	1	4213.0×	0.002	HPGD
ductus arteriosus closure	1	3370.4×	0.002	HPGD
thrombin-activated receptor signaling pathway	1	2407.4×	0.002	HPGD
parturition	1	1872.4×	0.002	HPGD
lipoxygenase pathway	1	1532.0×	0.002	HPGD
prostaglandin metabolic process	1	842.6×	0.003	HPGD
positive regulation of vascular associated smooth muscle cell proliferation	1	432.1×	0.005	HPGD
negative regulation of cell cycle	1	290.6×	0.006	HPGD
female pregnancy	1	210.7×	0.007	HPGD
response to estradiol	1	198.3×	0.007	HPGD
transforming growth factor beta receptor signaling pathway	1	159.0×	0.008	HPGD
response to ethanol	1	146.5×	0.008	HPGD
kidney development	1	140.4×	0.008	HPGD
response to lipopolysaccharide	1	124.8×	0.009	HPGD
positive regulation of apoptotic process	1	56.7×	0.018	HPGD

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.

Symbol	Example approved molecule
HPGD	PHENYLBUTAZONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HPGD	220	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PHENYLBUTAZONE	4	HPGD
CANDESARTAN CILEXETIL	4	HPGD
CHOLECALCIFEROL	4	HPGD
FLUORESCEIN	4	HPGD
OXAPROZIN	4	HPGD
BUMETANIDE	4	HPGD
SALMETEROL XINAFOATE	4	HPGD
DIBUCAINE	4	HPGD
INDIGOTINDISULFONATE	4	HPGD
CISPLATIN	4	HPGD
TETRABENAZINE	4	HPGD
TRIMETREXATE	4	HPGD
LABETALOL HYDROCHLORIDE	4	HPGD
PYRITHIONE ZINC	4	HPGD
DOXAZOSIN MESYLATE	4	HPGD
PRILOCAINE HYDROCHLORIDE	4	HPGD
TOLMETIN SODIUM	4	HPGD
CHLOROTRIANISENE	4	HPGD
TRAZODONE HYDROCHLORIDE	4	HPGD
DINOPROST TROMETHAMINE	4	HPGD
METHYSERGIDE MALEATE	4	HPGD
ETHOPROPAZINE HYDROCHLORIDE	4	HPGD
ACRISORCIN	4	HPGD
FLUOXETINE HYDROCHLORIDE	4	HPGD
LIOTHYRONINE SODIUM	4	HPGD
CARBIDOPA ANHYDROUS	4	HPGD
ETHOPROPAZINE	4	HPGD
ROSE BENGAL FREE ACID	4	HPGD
ROSIGLITAZONE	4	HPGD
RABEPRAZOLE	4	HPGD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HPGD	38	Binding:33, Functional:3, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HPGD	1.1.1.141, 1.3.1.48	15-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.

Compound	Max phase	Cohort target (bioactivity)
PHENYLBUTAZONE	4	HPGD
CANDESARTAN CILEXETIL	4	HPGD
CHOLECALCIFEROL	4	HPGD
FLUORESCEIN	4	HPGD
OXAPROZIN	4	HPGD
BUMETANIDE	4	HPGD
SALMETEROL XINAFOATE	4	HPGD
DIBUCAINE	4	HPGD
INDIGOTINDISULFONATE	4	HPGD
CISPLATIN	4	HPGD
TETRABENAZINE	4	HPGD
TRIMETREXATE	4	HPGD
LABETALOL HYDROCHLORIDE	4	HPGD
PYRITHIONE ZINC	4	HPGD
DOXAZOSIN MESYLATE	4	HPGD
PRILOCAINE HYDROCHLORIDE	4	HPGD
TOLMETIN SODIUM	4	HPGD
CHLOROTRIANISENE	4	HPGD
TRAZODONE HYDROCHLORIDE	4	HPGD
DINOPROST TROMETHAMINE	4	HPGD
METHYSERGIDE MALEATE	4	HPGD
ETHOPROPAZINE HYDROCHLORIDE	4	HPGD
ACRISORCIN	4	HPGD
FLUOXETINE HYDROCHLORIDE	4	HPGD
LIOTHYRONINE SODIUM	4	HPGD
CARBIDOPA ANHYDROUS	4	HPGD
ETHOPROPAZINE	4	HPGD
ROSE BENGAL FREE ACID	4	HPGD
ROSIGLITAZONE	4	HPGD
RABEPRAZOLE	4	HPGD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HPGD
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	0

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.