Camptodactyly-arthropathy-coxa vara-pericarditis syndrome

Summary

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (MONDO:0008828) is a disease caused by PRG4 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PRG4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 46
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0001225	Wrist swelling	Very frequent (80-99%)
HP:0001836	Camptodactyly of toe	Very frequent (80-99%)
HP:0002812	Coxa vara	Very frequent (80-99%)
HP:0002938	Lumbar hyperlordosis	Very frequent (80-99%)
HP:0003940	Osteoarthritis of the elbow	Very frequent (80-99%)
HP:0005086	Knee osteoarthritis	Very frequent (80-99%)
HP:0005195	Polyarticular arthropathy	Very frequent (80-99%)
HP:0008812	Flattened femoral head	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0000939	Osteoporosis	Frequent (30-79%)
HP:0012062	Bone cyst	Frequent (30-79%)
HP:0100864	Short femoral neck	Frequent (30-79%)
HP:0001634	Mitral valve prolapse	Occasional (5-29%)
HP:0001653	Mitral regurgitation	Occasional (5-29%)
HP:0001701	Pericarditis	Occasional (5-29%)
HP:0002102	Pleuritis	Occasional (5-29%)
HP:0002960	Autoimmunity	Excluded (0%)
HP:0033331	Acute phase response	Excluded (0%)
HP:0001541	Ascites	Very rare (<1-4%)
HP:0008610	Infantile sensorineural hearing impairment	Very rare (<1-4%)
HP:0100018	Nuclear cataract	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	camptodactyly-arthropathy-coxa vara-pericarditis syndrome
Mondo ID	MONDO:0008828
EFO	EFO:0009028
MeSH	C537560
OMIM	208250
Orphanet	2848
DOID	DOID:0090127
UMLS	C1859690
MedGen	349226
GARD	0000306
Is cancer (heuristic)	no

Also known as: arthropathy camptodactyly syndrome · arthropathy-camptodactyly syndrome · CACP · CACP syndrome · camptodactyly arthropathy coxa vara pericarditis syndrome · camptodactyly arthropathy pericarditis syndrome · camptodactyly-arthropathy-coxa vara-pericarditis syndrome · camptodactyly-arthropathy-coxa-vara-pericarditis syndrome · camptodactyly-arthropathy-pericarditis syndrome · fibrosing serositis, familial · Jacobs syndrome · PAC syndrome · pericarditis arthropathy camptodactyly syndrome · pericarditis-arthropathy-camptodactyly syndrome

Data availability: 46 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › rheumatic disorder › camptodactyly-arthropathy-coxa vara-pericarditis syndrome

Related subtypes (29): palindromic rheumatism, rheumatic pulmonary valve disease, lupus erythematosus, mixed connective tissue disease, Reye syndrome, Wissler syndrome, acroosteolysis dominant type, chondrocalcinosis 2, Gorham-Stout disease, rheumatoid arthritis, juvenile idiopathic arthritis, sweet syndrome, dermatomyositis, IL10-related early-onset inflammatory bowel disease, unexplained long-lasting fever/inflammatory syndrome, myalgia-eosinophilia syndrome associated with tryptophan, reactive arthritis, rheumatic fever, intermittent hydrarthrosis, fibroblastic rheumatism, interstitial granulomatous dermatitis with arthritis, scleroderma, idiopathic juvenile osteoporosis, polymyalgia rheumatica, autoinflammatory syndrome, progeria-associated arthropathy, LAMA5-related multisystemic syndrome, rheumatic disease of mitral valve, isolated sternocostoclavicular hyperostosis

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

46 retrieved; paginated sample, class counts are floors:

26 pathogenic, 7 likely pathogenic, 4 pathogenic/likely pathogenic, 4 benign, 3 uncertain significance, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1013543	NM_005807.6(PRG4):c.3496C>T (p.Arg1166Ter)	PRG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323494	NM_005807.6(PRG4):c.4064C>G (p.Ser1355Ter)	PRG4	Pathogenic	criteria provided, single submitter
1323495	NM_005807.6(PRG4):c.3486dup (p.Val1163fs)	PRG4	Pathogenic	criteria provided, single submitter
1323496	NM_005807.6(PRG4):c.1935del (p.Glu646fs)	PRG4	Pathogenic	criteria provided, multiple submitters, no conflicts
1333348	NM_005807.6(PRG4):c.2894_2898del (p.Thr965fs)	PRG4	Pathogenic	criteria provided, single submitter
1526151	NM_005807.6(PRG4):c.301G>T (p.Glu101Ter)	PRG4	Pathogenic	criteria provided, single submitter
2577870	NM_005807.6(PRG4):c.1134dup (p.Lys379fs)	PRG4	Pathogenic	criteria provided, single submitter
2577871	NM_005807.6(PRG4):c.1699del (p.Glu567fs)	PRG4	Pathogenic	criteria provided, single submitter
2577874	NM_005807.6(PRG4):c.2816_2817del (p.Lys939fs)	PRG4	Pathogenic	criteria provided, single submitter
4293731	NM_005807.6(PRG4):c.6_7dup (p.Trp3fs)	PRG4	Pathogenic	criteria provided, single submitter
5651	NM_005807.6(PRG4):c.2806_2810del (p.Lys936fs)	PRG4	Pathogenic	no assertion criteria provided
5653	PRG4, 2-BP DEL, NT3023	PRG4	Pathogenic	no assertion criteria provided
5655	NM_005807.6(PRG4):c.4190_4191delinsAG (p.Ser1397Ter)	PRG4	Pathogenic	no assertion criteria provided
5656	PRG4, IVS6, 41-BP INS	PRG4	Pathogenic	no assertion criteria provided
599362	NC_000001.10:g.(?186265850)(186266785_?)del	PRG4	Pathogenic	no assertion criteria provided
684664	NM_005807.6(PRG4):c.1194del (p.Thr399fs)	PRG4	Pathogenic	no assertion criteria provided
684665	NM_005807.6(PRG4):c.3917_3934del (p.Arg1306_Ser1311del)	PRG4	Pathogenic	no assertion criteria provided
684666	NM_005807.6(PRG4):c.3277_3278del (p.Lys1093fs)	PRG4	Pathogenic	no assertion criteria provided
684667	NM_005807.6(PRG4):c.4101C>G (p.Tyr1367Ter)	PRG4	Pathogenic	no assertion criteria provided
684668	NM_005807.6(PRG4):c.2215A>T (p.Lys739Ter)	PRG4	Pathogenic	no assertion criteria provided
684669	NM_005807.6(PRG4):c.1911del (p.Glu638fs)	PRG4	Pathogenic	no assertion criteria provided
684670	NM_005807.6(PRG4):c.1910_1911del (p.Pro637fs)	PRG4	Pathogenic	criteria provided, single submitter
684671	NM_005807.6(PRG4):c.2841_2842del (p.Lys947fs)	PRG4	Pathogenic	no assertion criteria provided
684672	NM_005807.6(PRG4):c.849del (p.Val284fs)	PRG4	Pathogenic	no assertion criteria provided
800914	NM_005807.6(PRG4):c.3139_3140del (p.Lys1047fs)	PRG4	Pathogenic	no assertion criteria provided
801585	NM_005807.6(PRG4):c.3756dup (p.Lys1253Ter)	PRG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973566	NM_005807.6(PRG4):c.3462_3465del (p.Thr1155fs)	PRG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
974887	NM_005807.6(PRG4):c.3254_3260dup (p.Val1088fs)	PRG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
987918	NM_005807.6(PRG4):c.1320dup (p.Lys441fs)	PRG4	Pathogenic	criteria provided, multiple submitters, no conflicts
992974	NM_005807.6(PRG4):c.3254_3260del (p.Asn1084_Ser1085insTer)	PRG4	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PRG4	Definitive	Autosomal recessive	camptodactyly-arthropathy-coxa vara-pericarditis syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRG4	Orphanet:2848	Camptodactyly-arthropathy-coxa-vara-pericarditis syndrome

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
PRG4	HGNC:9364	ENSG00000116690	Q92954	Proteoglycan 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRG4	Proteoglycan 4	Plays a role in boundary lubrication within articulating joints.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRG4	Other/Unknown	no		Hemopexin-like_dom, Somatomedin_B_dom, Hemopexin_CS

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
calcaneal tendon	1
pericardium	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRG4	176	tissue_specific	marker	synovial joint, calcaneal tendon, pericardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRG4	811

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRG4	Q92954	48.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
immune response	1	47.1×	0.021	PRG4

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
PRG4	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	0
E	Difficult family or no structure, no drug	1	PRG4

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)
PRG4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.