Enthesitis

Summary

Enthesitis (MONDO:0024419) is a disease with 1 cohort gene and 10 clinical trials. Top therapeutic interventions include secukinumab, golimumab, and certolizumab.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	enthesitis
Mondo ID	MONDO:0024419
NCIT	C114470
SNOMED CT	359643005
UMLS	C1282952
MedGen	451081
Is cancer (heuristic)	no

Also known as: enthesis inflammation · enthesitis · inflammation of enthesis · inflammatory enthesopathy

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › enthesopathy › enthesitis

Related subtypes (4): pes anserinus tendinitis or bursitis, olecranon bursitis, tibial collateral ligament bursitis, fibular collateral ligament bursitis

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 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

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: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE4	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04887597	PHASE4	UNKNOWN	EBIO - Enthesitis Biopsy Study
NCT04953871	PHASE4	COMPLETED	Enthesitis Assessment Before and After Anti-Tumor Necrosis Factor Treatment in Spondyloarthritis
NCT02771210	PHASE3	COMPLETED	Study of Efficacy and Safety of Secukinumab in Psoriatic Arthritis and Axial Spondyloarthritis Patients With Active Enthesitis Including One Achilles Tendon Site
NCT03248284	Not specified	RECRUITING	Immune-Competent Cell Manifestations in Psoriatic Arthritis Achilles Tendons
NCT06987292	Not specified	RECRUITING	A Prospective Study to Assess the Efficacy of IL-17 Inhibitors on Subclinical Enthesitis in Patients With Moderate to Severe Psoriasis Based on Power Doppler (PD) Ultrasonography (PDUS)
NCT03955861	Not specified	COMPLETED	Ultrasound Enthesitis Response in Psoriatic Arthritis
NCT04209894	Not specified	COMPLETED	Detection of Subclinical Enthesitis by Ultrasonography
NCT04224597	Not specified	UNKNOWN	Evaluation of the Presence of Enthesitis in Patients With Acne Vulgaris
NCT04946539	Not specified	COMPLETED	Value of Ultrasonographic Enthesitis Assessment in Spondyloarthritis
NCT05942976	Not specified	COMPLETED	Enthesis Differences in Rheumatoid Arthritis and Axial Spondyloarthropathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SECUKINUMAB	4	3
GOLIMUMAB	4	1
CERTOLIZUMAB	3	1