Hypertrophic osteoarthropathy, primary, autosomal recessive, 2

Summary

Hypertrophic osteoarthropathy, primary, autosomal recessive, 2 (MONDO:0013756) is a disease caused by SLCO2A1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SLCO2A1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic osteoarthropathy, primary, autosomal recessive, 2
Mondo ID	MONDO:0013756
OMIM	614441
UMLS	C3280800
MedGen	482430
GARD	0015805
Is cancer (heuristic)	no

Also known as: hypertrophic osteoarthropathy, primary, autosomal recessive 2 · hypertrophic osteoarthropathy, primary, autosomal recessive, 2 · hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 · PHOAR2 · primary hypertrophic osteoarthropathy caused by mutation in SLCO2A1 · SLCO2A1 primary hypertrophic osteoarthropathy

Data availability: 67 ClinVar variants · 5 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, 2

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

67 retrieved; paginated sample, class counts are floors:

30 pathogenic, 18 likely pathogenic, 8 uncertain significance, 4 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2920746	NM_005630.3(SLCO2A1):c.1372G>T (p.Val458Phe)	LOC123038185	Pathogenic	no assertion criteria provided
1174120	NM_005630.3(SLCO2A1):c.861+2T>C	SLCO2A1	Pathogenic	no assertion criteria provided
1174123	NM_005630.3(SLCO2A1):c.621C>A (p.Tyr207Ter)	SLCO2A1	Pathogenic	no assertion criteria provided
1174124	NM_005630.3(SLCO2A1):c.1660G>A (p.Gly554Arg)	SLCO2A1	Pathogenic	criteria provided, single submitter
1174125	NM_005630.3(SLCO2A1):c.1814+1G>A	SLCO2A1	Pathogenic	no assertion criteria provided
1350810	NM_005630.3(SLCO2A1):c.310G>A (p.Gly104Arg)	SLCO2A1	Pathogenic	criteria provided, single submitter
1483488	NM_005630.3(SLCO2A1):c.1106G>A (p.Gly369Asp)	SLCO2A1	Pathogenic	criteria provided, single submitter
1978090	NM_005630.3(SLCO2A1):c.1768del (p.Arg590fs)	SLCO2A1	Pathogenic	criteria provided, single submitter
2203442	NM_005630.3(SLCO2A1):c.1771C>T (p.Arg591Ter)	SLCO2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225477	NM_005630.3(SLCO2A1):c.1807C>T (p.Arg603Ter)	SLCO2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225478	NM_005630.3(SLCO2A1):c.940+1G>A	SLCO2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2920730	NM_005630.3(SLCO2A1):c.421G>T (p.Glu141Ter)	SLCO2A1	Pathogenic	no assertion criteria provided
2920732	NM_005630.3(SLCO2A1):c.1106-1G>A	SLCO2A1	Pathogenic	no assertion criteria provided
2920734	NM_005630.3(SLCO2A1):c.178G>A (p.Glu60Lys)	SLCO2A1	Pathogenic	no assertion criteria provided
2920736	NM_005630.3(SLCO2A1):c.759G>A (p.Trp253Ter)	SLCO2A1	Pathogenic	no assertion criteria provided
2920737	NM_005630.3(SLCO2A1):c.440G>A (p.Trp147Ter)	SLCO2A1	Pathogenic	criteria provided, single submitter
2920740	NM_005630.3(SLCO2A1):c.1095C>A (p.Asn365Lys)	SLCO2A1	Pathogenic	no assertion criteria provided
2920742	NM_005630.3(SLCO2A1):c.1668G>C (p.Gln556His)	SLCO2A1	Pathogenic	no assertion criteria provided
2920743	NM_005630.3(SLCO2A1):c.763G>A (p.Gly255Arg)	SLCO2A1	Pathogenic	no assertion criteria provided
2920744	NM_005630.3(SLCO2A1):c.855del (p.Ala286fs)	SLCO2A1	Pathogenic	no assertion criteria provided
2920745	NM_005630.3(SLCO2A1):c.1461+1G>C	SLCO2A1	Pathogenic	no assertion criteria provided
30186	NM_005630.3(SLCO2A1):c.97-1G>A	SLCO2A1	Pathogenic	no assertion criteria provided
30187	NM_005630.3(SLCO2A1):c.764G>A (p.Gly255Glu)	SLCO2A1	Pathogenic	criteria provided, single submitter
30188	NM_005630.3(SLCO2A1):c.1634del (p.Asn545fs)	SLCO2A1	Pathogenic	criteria provided, single submitter
37167	NM_005630.3(SLCO2A1):c.830dup (p.Phe278fs)	SLCO2A1	Pathogenic	criteria provided, single submitter
37168	NM_005630.3(SLCO2A1):c.754C>T (p.Arg252Ter)	SLCO2A1	Pathogenic	no assertion criteria provided
37169	NM_005630.3(SLCO2A1):c.1259G>T (p.Cys420Phe)	SLCO2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37170	NM_005630.3(SLCO2A1):c.253A>T (p.Ile85Phe)	SLCO2A1	Pathogenic	no assertion criteria provided
37171	NM_005630.3(SLCO2A1):c.310G>T (p.Gly104Ter)	SLCO2A1	Pathogenic	criteria provided, single submitter
4292998	NM_005630.3(SLCO2A1):c.1293del (p.Ser432fs)	SLCO2A1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
SLCO2A1	Definitive	Autosomal dominant	hypertrophic osteoarthropathy, primary, autosomal dominant	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLCO2A1	Orphanet:2796	Pachydermoperiostosis
SLCO2A1	Orphanet:468641	Chronic enteropathy associated with SLCO2A1 gene

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
SLCO2A1	HGNC:10955	ENSG00000174640	Q92959	Solute carrier organic anion transporter family member 2A1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLCO2A1	Solute carrier organic anion transporter family member 2A1	Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLCO2A1	Transporter	yes		Kazal_dom, OATP, MFS_dom

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
right lung	1
upper lobe of left lung	1
upper lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLCO2A1	252	broad	marker	right lung, upper lobe of left lung, upper lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLCO2A1	1,123

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLCO2A1	Q92959	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2)	1	11420.0×	7e-04	SLCO2A1
Organic anion transport by SLCO transporters	1	1038.2×	0.004	SLCO2A1
Transport of vitamins, nucleosides, and related molecules	1	271.9×	0.010	SLCO2A1
SLC transporter disorders	1	203.9×	0.010	SLCO2A1
Disorders of transmembrane transporters	1	139.3×	0.011	SLCO2A1
SLC-mediated transmembrane transport	1	59.2×	0.023	SLCO2A1
Transport of small molecules	1	25.1×	0.045	SLCO2A1
Disease	1	13.1×	0.076	SLCO2A1

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
prostaglandin transport	1	1872.4×	0.001	SLCO2A1
sodium-independent organic anion transport	1	1123.5×	0.001	SLCO2A1
lipid transport	1	263.3×	0.004	SLCO2A1

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
SLCO2A1	DINOPROST

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLCO2A1	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DINOPROST	4	SLCO2A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLCO2A1	4	Functional:4

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

1 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)
DINOPROST	4	SLCO2A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLCO2A1
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.