Isolated congenital digital clubbing

Summary

Isolated congenital digital clubbing (MONDO:0007343) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 61
• Phenotypes (HPO): 17

Clinical features

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0003549	Abnormality of connective tissue	Very frequent (80-99%)
HP:0001500	Broad finger	Frequent (30-79%)
HP:0001795	Hyperconvex nail	Frequent (30-79%)
HP:0001805	Onychogryposis	Frequent (30-79%)
HP:0001821	Broad nail	Frequent (30-79%)
HP:0001837	Broad toe	Frequent (30-79%)
HP:0002164	Nail dysplasia	Frequent (30-79%)
HP:0011300	Broad fingertip	Frequent (30-79%)
HP:0011304	Broad thumb	Frequent (30-79%)
HP:0100759	Clubbing of fingers	Frequent (30-79%)
HP:0100760	Clubbing of toes	Frequent (30-79%)
HP:0008391	Dystrophic fingernails	Occasional (5-29%)
HP:0012203	Onychomycosis	Occasional (5-29%)
HP:0000951	Abnormality of the skin	Excluded (0%)
HP:0000975	Hyperhidrosis	Excluded (0%)
HP:0002653	Bone pain	Excluded (0%)
HP:0002829	Arthralgia	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated congenital digital clubbing
Mondo ID	MONDO:0007343
OMIM	119900
Orphanet	217059
ICD-11	130631845
UMLS	C0345408
MedGen	576901
GARD	0017117
Is cancer (heuristic)	no

Also known as: isolated congenital acropachy · isolated congenital nail clubbing

Data availability: 61 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › nail disorder › inherited isolated nail anomaly › isolated congenital digital clubbing

Related subtypes (8): nonsyndromic congenital nail disorder 2, nonsyndromic congenital nail disorder 3, nonsyndromic congenital nail disorder 1, nonsyndromic congenital nail disorder 5, nonsyndromic congenital nail disorder 7, nonsyndromic congenital nail disorder 8, leukonychia totalis, isolated congenital anonychia

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

61 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 9 benign, 8 likely benign, 3 benign/likely benign, 3 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
156027	NM_000860.6(HPGD):c.310_311del (p.Leu104fs)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
7919	NM_000860.6(HPGD):c.175_176del (p.Leu59fs)	HPGD	Pathogenic	criteria provided, multiple submitters, no conflicts
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
7920	NM_000860.6(HPGD):c.577T>C (p.Ser193Pro)	HPGD	Likely pathogenic	criteria provided, single submitter
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
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
348178	NM_000860.6(HPGD):c.*1246G>A	HPGD	Uncertain significance	criteria provided, single submitter
348179	NM_000860.6(HPGD):c.*1203A>C	HPGD	Uncertain significance	criteria provided, single submitter
348181	NM_000860.6(HPGD):c.*1131C>T	HPGD	Uncertain significance	criteria provided, single submitter
348182	NM_000860.6(HPGD):c.*968T>C	HPGD	Uncertain significance	criteria provided, single submitter
348183	NM_000860.6(HPGD):c.*941C>T	HPGD	Uncertain significance	criteria provided, single submitter
348184	NM_000860.6(HPGD):c.*914A>G	HPGD	Uncertain significance	criteria provided, single submitter
348186	NM_000860.6(HPGD):c.*749A>G	HPGD	Uncertain significance	criteria provided, single submitter
348187	NM_000860.6(HPGD):c.*679T>C	HPGD	Uncertain significance	criteria provided, single submitter
348190	NM_000860.6(HPGD):c.*510G>C	HPGD	Uncertain significance	criteria provided, single submitter
348192	NM_000860.6(HPGD):c.*248A>G	HPGD	Uncertain significance	criteria provided, single submitter
348194	NM_000860.6(HPGD):c.*157A>G	HPGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
348198	NM_000860.6(HPGD):c.*54A>T	HPGD	Uncertain significance	criteria provided, single submitter
348199	NM_000860.6(HPGD):c.773C>A (p.Thr258Lys)	HPGD	Uncertain significance	criteria provided, single submitter
348201	NM_000860.6(HPGD):c.520A>C (p.Ser174Arg)	HPGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
348203	NM_000860.6(HPGD):c.421G>A (p.Gly141Arg)	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	Supportive	Autosomal dominant	isolated congenital digital clubbing	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.