Synovitis

Summary

Synovitis (MONDO:0002400) is a disease with 1 cohort gene (9 GWAS associations across 13 studies) and 20 clinical trials. Top therapeutic interventions include sumatriptan, tizanidine, and baclofen.

At a glance

• Cohort genes: 1
• GWAS associations: 9
• ClinVar variants: 1
• Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	synovitis
Mondo ID	MONDO:0002400
EFO	EFO:0008997
MeSH	D013585
DOID	DOID:2703
NCIT	C50766
SNOMED CT	416209007
UMLS	C0039103
MedGen	21051
Is cancer (heuristic)	no

Also known as: inflammation of synovial membrane of synovial joint · synovial membrane of synovial joint inflammation · Synovitides · synovitis · synovitis (disease)

Data availability: 1 ClinVar variant · 9 GWAS associations (13 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › synovitis

Related subtypes (15): benign connective and soft tissue neoplasm, ochronosis disorder, enthesopathy, collagenopathy, fasciitis, interstitial keratitis, periostitis, rheumatic disorder, panniculitis, ainhum, overlapping connective tissue disease, interstitial cystitis, connective tissue neoplasm, hereditary disorder of connective tissue, disease of the tendon

Subtypes (1): gonococcal synovitis

Genetics & variants

GWAS landscape

9 GWAS associations across 13 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr2:217270265	4e-10		T	0.09
rs198462	2e-09	MYRF-AS1, MYRF	?
chr16:69853804	3e-09		G	0.06
chr16:53869541	9e-09		G	0.06
chr11:89487921	1e-08		T	0.08
chr2:33167844	1e-08		A	0.06
chr5:122074834	2e-08		G	0.08
chr6:94087389	2e-08		A	0.55
chr7:138045284	4e-08		T	1.4

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90474099	UK Biobank Whole-Genome Sequencing Consortium	2025	18,977	439,463	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667908	UK Biobank Whole-Genome Sequencing Consortium	2025	18,977	439,463	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90726747	Kim HI	2026	10,235	33,791	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90080520	Backman JD	2021	8,632	371,813	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084506	Backman JD	2021	8,632	371,813	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90651333	Liu TY	2025	3,960	210,582	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90727094	Kim HI	2026	2,829	41,197	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90080519	Backman JD	2021	2,614	385,133	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084505	Backman JD	2021	2,614	385,133	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080518	Backman JD	2021	944	386,986	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	9

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	8

Functional consequences

Consequence	Count
unknown	8
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr2:217270265							4e-10	Tier 4: intronic/intergenic
rs198462	11	61756647	G>A,C,T	0.05	intron_variant	MYRF-AS1, MYRF	2e-09	Tier 4: intronic/intergenic
chr16:69853804							3e-09	Tier 4: intronic/intergenic
chr16:53869541							9e-09	Tier 4: intronic/intergenic
chr11:89487921							1e-08	Tier 4: intronic/intergenic
chr2:33167844							1e-08	Tier 4: intronic/intergenic
chr5:122074834							2e-08	Tier 4: intronic/intergenic
chr6:94087389							2e-08	Tier 4: intronic/intergenic
chr7:138045284							4e-08	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
684430	NM_005045.4(RELN):c.7456A>G (p.Ser2486Gly)	RELN	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RELN	Orphanet:101046	Epilepsy with auditory features
RELN	Orphanet:89844	Lissencephaly syndrome, Norman-Roberts type

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
RELN	HGNC:9957	ENSG00000189056	P78509	Reelin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RELN	Reelin	Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.

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)
RELN	Other/Unknown	no		EGF, Reeler_dom, EGF_extracell

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
cerebellar vermis	1
cerebellum	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RELN	254	broad	marker	olfactory bulb, cerebellar vermis, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RELN	2,305

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RELN	P78509	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Reelin signalling pathway	1	1903.3×	5e-04	RELN

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
spinal cord patterning	1	16852.0×	0.001	RELN
positive regulation of lateral motor column neuron migration	1	16852.0×	0.001	RELN
lateral motor column neuron migration	1	5617.3×	0.002	RELN
cerebral cortex tangential migration	1	4213.0×	0.002	RELN
regulation of synaptic activity	1	4213.0×	0.002	RELN
NMDA glutamate receptor clustering	1	3370.4×	0.002	RELN
postsynaptic density protein 95 clustering	1	2808.7×	0.002	RELN
positive regulation of small GTPase mediated signal transduction	1	2106.5×	0.002	RELN
receptor localization to synapse	1	2106.5×	0.002	RELN
ventral spinal cord development	1	1872.4×	0.002	RELN
positive regulation of synapse maturation	1	1872.4×	0.002	RELN
postsynaptic density assembly	1	1872.4×	0.002	RELN
radial glial cell differentiation	1	1532.0×	0.002	RELN
interneuron migration	1	1532.0×	0.002	RELN
regulation of behavior	1	1404.3×	0.002	RELN
reelin-mediated signaling pathway	1	1203.7×	0.002	RELN
layer formation in cerebral cortex	1	1123.5×	0.002	RELN
glial cell differentiation	1	887.0×	0.002	RELN
response to pain	1	887.0×	0.002	RELN
positive regulation of dendritic spine morphogenesis	1	887.0×	0.002	RELN
protein localization to synapse	1	766.0×	0.003	RELN
regulation of neuron differentiation	1	732.7×	0.003	RELN
positive regulation of long-term synaptic potentiation	1	674.1×	0.003	RELN
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.003	RELN
regulation of neuron migration	1	624.1×	0.003	RELN
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	RELN
positive regulation of TOR signaling	1	495.6×	0.003	RELN
associative learning	1	481.5×	0.003	RELN
long-term memory	1	421.3×	0.004	RELN
dendrite development	1	391.9×	0.004	RELN

Therapeutics

Drugs indicated for this disease

4 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Etanercept.

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
RELN	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	RELN

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)
RELN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	14
PHASE3	2
PHASE2	2
PHASE4	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04641351	PHASE4	ACTIVE_NOT_RECRUITING	Corticosteroid Meniscectomy Randomized Trial
NCT00604539	PHASE3	COMPLETED	Effect of Chondroitin Sulphate on Synovial Inflammation in Patients With Osteoarthritis of the Knee
NCT07328022	PHASE3	COMPLETED	Efficacy and Safety of Etoricoxib/Betamethasone Combination in Acute Bursitis, Tendinitis and Synovitis
NCT00001677	PHASE2	COMPLETED	Methotrexate Alone Versus Combination of Methotrexate and Subcutaneous Fludarabine for Severe Rheumatoid Arthritis: Safety, Tolerance and Efficacy
NCT01272830	PHASE2	COMPLETED	Double-Blinded Clinical Trial Using Apatone®B for Symptomatic Postoperative Total Joint Replacements
NCT02060305	PHASE1	TERMINATED	Intra-articular Bevacizumab for Recurrent Hemarthroses at Target Joints With Chronic Hemophilic Synovitis
NCT05629130	Not specified	RECRUITING	Embolization in Hereditary Coagulopathies
NCT05700682	Not specified	RECRUITING	Perfusion MRI-targeted Joint Embolization for Chronic Musculoskeletal Pain of the Shoulder, Hip and Knee
NCT06352216	Not specified	RECRUITING	Prevalence of Synovitis in Patients With Haemophilia A
NCT06737952	Not specified	NOT_YET_RECRUITING	Cellular and Molecular Analysis of Synovial Tissue of Patients With Arthritis
NCT07187661	Not specified	RECRUITING	Intra-Articular Bevacizumab for Preventing Recurrent Hemarthrosis in Hemophilia With Chronic Synovitis
NCT00001375	Not specified	COMPLETED	The Pathogenesis of Inflammatory Synovitis: A Study of Early Arthritis
NCT00001679	Not specified	COMPLETED	Prognostic Indicators and Determinants of the 2-5 Year Outcome in a Cohort of Early Synovitis Patients
NCT00890058	Not specified	COMPLETED	A Case Control Study to Define Clinical, Immunologic and Radiographic Features of the Aromatase Inhibitor Arthralgia Syndrome
NCT00903903	Not specified	UNKNOWN	Computer-Assisted Quantification of the Synovial Perfusion in Patients With Arthritis Using Two-Dimensional and Three-Dimensional Power Doppler Ultrasonography
NCT01731262	Not specified	UNKNOWN	Preliminary Study of Sonic Hedgehog Signaling Pathway in the Pathogenesis of Rheumatoid Arthritis
NCT02403687	Not specified	COMPLETED	Prospective Analgesic Compound Efficacy (PACE) Study
NCT02902562	Not specified	COMPLETED	Synovitis and Therapy Response in Inflammatory Arthritis With Contrast Enhanced Ultrasound
NCT03507933	Not specified	UNKNOWN	Evaluation of the Effectiveness of Surgical Treatment of Villo-nodular Synovitis of the Hip in Children
NCT04750993	Not specified	COMPLETED	Comparison of the Frequency of Subclinic Synovitis in the Distal Interphalangeal Joints of the Hand in Psoriasis Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUMATRIPTAN	4	3
TIZANIDINE	4	2
BACLOFEN	4	1
BETAMETHASONE	4	1
CYCLOBENZAPRINE	4	1
ESFLURBIPROFEN	4	1
ETORICOXIB	4	1
FLURBIPROFEN	4	1
MELOXICAM	4	1
MENTHOL	4	1
PRILOCAINE	4	1
LEVOMENTHOL	3	1
ZUCAPSAICIN	3	1