Polyarticular arthritis

Summary

Polyarticular arthritis (MONDO:0024280) is a disease with 1 cohort gene and 22 clinical trials. Top therapeutic interventions include methotrexate and varicella zoster virus envelope glycoprotein e.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polyarticular arthritis
Mondo ID	MONDO:0024280
NCIT	C26996
SNOMED CT	416956002
UMLS	C0162323
MedGen	56408
Is cancer (heuristic)	no

Also known as: polyarthritis · polyarticular arthritis

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone inflammation disease › arthritic joint disease › polyarticular arthritis

Related subtypes (12): chondrocalcinosis, transient arthritis, synovitis, osteoarthritis, periarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, reactive arthritis, adult-onset Still disease, infective arthritis, negative rheumatoid factor polyarthritis, hemophilic arthropathy

Subtypes (2): rheumatoid nodulosis, juvenile chronic polyarthritis

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
812547	NM_000651.6(CR1):c.6283C>A (p.His2095Asn)	CR1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
CR1	HGNC:2334	ENSG00000203710	P17927	Complement receptor type 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CR1	Complement receptor type 1	Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages.

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
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CR1	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators

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
blood	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CR1	184	broad	marker	blood, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CR1	1,218

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CR1	P17927	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	1142.0×	0.003	CR1
Regulation of Complement cascade	1	233.1×	0.006	CR1
Neutrophil degranulation	1	23.1×	0.043	CR1

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 complex clearance by erythrocytes	1	16852.0×	5e-04	CR1
negative regulation of serine-type endopeptidase activity	1	16852.0×	5e-04	CR1
organ or tissue specific immune response	1	8426.0×	5e-04	CR1
immune complex clearance	1	8426.0×	5e-04	CR1
negative regulation of plasma cell differentiation	1	8426.0×	5e-04	CR1
positive regulation of activation of membrane attack complex	1	5617.3×	5e-04	CR1
negative regulation of activation of membrane attack complex	1	5617.3×	5e-04	CR1
negative regulation of complement activation, alternative pathway	1	5617.3×	5e-04	CR1
positive regulation of serine-type endopeptidase activity	1	5617.3×	5e-04	CR1
negative regulation of complement activation	1	3370.4×	7e-04	CR1
negative regulation of complement-dependent cytotoxicity	1	3370.4×	7e-04	CR1
negative regulation of complement activation, classical pathway	1	2407.4×	9e-04	CR1
negative regulation of immunoglobulin production	1	2106.5×	9e-04	CR1
ATP export	1	1685.2×	0.001	CR1
glomerulus development	1	1296.3×	0.001	CR1
complement receptor mediated signaling pathway	1	1123.5×	0.001	CR1
T cell mediated immunity	1	991.3×	0.001	CR1
complement activation, alternative pathway	1	991.3×	0.001	CR1
positive regulation of regulatory T cell differentiation	1	936.2×	0.001	CR1
plasma membrane organization	1	887.0×	0.001	CR1
complement activation	1	624.1×	0.002	CR1
negative regulation of interleukin-2 production	1	581.1×	0.002	CR1
complement activation, classical pathway	1	543.6×	0.002	CR1
negative regulation of type II interferon production	1	383.0×	0.003	CR1
negative regulation of T cell proliferation	1	330.4×	0.003	CR1
positive regulation of cell population proliferation	1	33.6×	0.030	CR1

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CR1	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	1	CR1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	16
PHASE4	2
PHASE1/PHASE2	2
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06763783	PHASE4	ENROLLING_BY_INVITATION	Vaccination Against Herpes Zoster in Patients With Inflammatory Rheumatic Diseases
NCT00920478	PHASE4	UNKNOWN	Targeting Synovitis in Early Rheumatoid Arthritis
NCT01068405	PHASE3	UNKNOWN	Erosive Osteoarthritis of the Hands: Treatment by Methotrexate Versus Placebo
NCT00023205	PHASE2	COMPLETED	Impact of Literacy Level on Patient Education and Health Among People With Arthritis
NCT00372177	PHASE1/PHASE2	COMPLETED	The Use of Anti-CD4 Monoclonal Antibody (mAb)-Fragment for the Imaging of Chronic Inflammation in Patients With Active Rheumatoid Arthritis
NCT02418273	PHASE1/PHASE2	WITHDRAWN	Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders
NCT02255383	Not specified	ACTIVE_NOT_RECRUITING	Persona Total Knee Arthroplasty Outcomes Study
NCT02337244	Not specified	ACTIVE_NOT_RECRUITING	Zimmer POLAR Persona - TKA (EMEA Study)
NCT04817969	Not specified	ACTIVE_NOT_RECRUITING	Persona Ti-Nidium Post-Market Clinical Follow-up
NCT05630053	Not specified	ACTIVE_NOT_RECRUITING	Cemented vs Cementless Persona Keel RCT
NCT05787821	Not specified	RECRUITING	Persona OsseoTi Keel Compatibility Study (Total Knee Arthroplasty)
NCT07286513	Not specified	ENROLLING_BY_INVITATION	Persona SoluTion PPS Femur PMCF
NCT00623922	Not specified	COMPLETED	Effect of Patient Education in Rheumatic Diseases
NCT01859130	Not specified	COMPLETED	Zimmer POLAR - Total Knee Arthroplasty (TKA)
NCT03224689	Not specified	UNKNOWN	Evaluation of The Safety And Performance of The Freedom Total Knee® System With The PEEK-OPTIMA Femoral Component
NCT03272373	Not specified	COMPLETED	NexGen TM Tibia Clinical Outcomes Study
NCT03589300	Not specified	COMPLETED	Persona TM Tibia Clinical Outcomes Study
NCT04586933	Not specified	UNKNOWN	Nutrition in Rheumatic Diseases
NCT04688398	Not specified	UNKNOWN	Study of the Impact of Fatty Acids From Seal Oil on the Relief of Symptoms Associated With Rheumatoid Arthritis
NCT06235710	Not specified	COMPLETED	Prevalence of Musculoskeletal Complaints in Nursing Home Residents
NCT06568029	Not specified	COMPLETED	Construct Validity and Responsiveness of EQ-5D-3L in Patients With Rheumatic Disease
NCT07580092	Not specified	COMPLETED	Construct Validity and Responsiveness of EQ-5D-3L and EQ-5D-5L in Patients With Inflammatory Joint Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
METHOTREXATE	4	1
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	1