Inclusion body myositis

Summary

Inclusion body myositis (MONDO:0007827) is a disease with 3 cohort genes (5 GWAS associations across 1 studies) and 73 clinical trials. Top therapeutic interventions include arimoclomol, anakinra, and natalizumab.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• GWAS associations: 5
• ClinVar variants: 3
• Phenotypes (HPO): 14
• Clinical trials: 73

Clinical features

Epidemiology

Prevalence records

7 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.5	Europe	Validated
Annual incidence	1-9 / 1 000 000	2.5	Sweden	Validated
Point prevalence	1-9 / 1 000 000	0.49	Netherlands	Validated
Point prevalence	1-9 / 100 000	1.1	United States	Validated
Point prevalence	1-9 / 1 000 000	0.1	Turkey	Validated
Point prevalence	1-9 / 100 000	3.2	Sweden	Validated
Point prevalence	1-9 / 100 000	1.2	Australia	Not yet validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0002960	Autoimmunity	Very frequent (80-99%)
HP:0003200	Ragged-red muscle fibers	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0003457	EMG abnormality	Very frequent (80-99%)
HP:0003701	Proximal muscle weakness	Very frequent (80-99%)
HP:0003731	Quadriceps muscle weakness	Very frequent (80-99%)
HP:0003805	Rimmed vacuoles	Very frequent (80-99%)
HP:0004303	Abnormal muscle fiber morphology	Very frequent (80-99%)
HP:0009071	Inflammatory myopathy	Very frequent (80-99%)
HP:0001315	Reduced tendon reflexes	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0034153	Anti-cytosolic-5-nucleotidase-1A antibody positivity	Frequent (30-79%)
HP:0003326	Myalgia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	inclusion body myositis
Mondo ID	MONDO:0007827
EFO	EFO:0007323
MeSH	D018979
OMIM	147421
Orphanet	611
DOID	DOID:3429
ICD-10-CM	G72.41
NCIT	C84786
SNOMED CT	72315009
UMLS	C0238190
MedGen	68659
GARD	0003896
MedDRA	10066407
NORD	1734
Is cancer (heuristic)	no

Also known as: IBM · inclusion body myositis · inflammatory myopathy · sIBM · Sporadic Inclusion Body Myositis · sporadic inclusion body myositis

Data availability: 3 ClinVar variants · 5 GWAS associations (1 study) · 1 GenCC gene-disease record · 7 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › myositis disease › inclusion body myositis

Related subtypes (10): idiopathic granulomatous myositis, myositis ossificans, tendinitis, myositis fibrosa, viral myositis, bacterial myositis, fungal myositis, infectious myositis, orbital myositis, idiopathic inflammatory myopathy

Subtypes (2): myopathy, proximal, and ophthalmoplegia, GNE myopathy

Genetics & variants

GWAS landscape

5 GWAS associations across 1 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
rs4713570	4e-45	HLA-DQA1 - HLA-DQB1	?	4.15
rs41490645	6e-07	CCR5AS	?	0.45
rs7568633	3e-06	LINC01101 - Y_RNA	?	0.71
rs12442533	8e-06	SLC28A2-AS1	?	0.71
rs13172971	1e-05	TMEM174 - LINC02230	?	1.55

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90270220	Rothwell S	2022	252	10,260	Genome-wide imputation identifies novel associations and localises signals in idiopathic inflammatory myopathies.

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	5

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	4
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4713570	6	32658263	C>G,T	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	4e-45	Tier 4: intronic/intergenic
rs41490645	3	46368646	A>C	0.05	intron_variant	CCR5AS	6e-07	Tier 4: intronic/intergenic
rs7568633	2	120564462	T>A,C	0.05	intron_variant	LINC01101 - Y_RNA	3e-06	Tier 4: intronic/intergenic
rs12442533	15	45237433	G>A,C,T	0.05	intron_variant	SLC28A2-AS1	8e-06	Tier 4: intronic/intergenic
rs13172971	5	73285961	G>A,C	0.05	intron_variant	TMEM174 - LINC02230	1e-05	Tier 4: intronic/intergenic

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
438624	NM_001128227.3(GNE):c.51+10408_52-10008del	GNE	Pathogenic	criteria provided, single submitter
3383300	NM_031462.4(CD99L2):c.68-5755G>T	CD99L2	Uncertain significance	criteria provided, single submitter
4819588	NM_007375.4(TARDBP):c.1127G>T (p.Gly376Val)	TARDBP	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 6 · 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
TARDBP	Limited	Autosomal dominant	inclusion body myositis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TARDBP	Orphanet:275872	Frontotemporal dementia with motor neuron disease
TARDBP	Orphanet:700154	TARDBP-related predominantly upper-limb distal myopathy
TARDBP	Orphanet:803	Amyotrophic lateral sclerosis
GNE	Orphanet:3166	Sialuria
GNE	Orphanet:438207	Severe autosomal recessive macrothrombocytopenia
GNE	Orphanet:602	GNE myopathy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TARDBP	HGNC:11571	ENSG00000120948	Q13148	TAR DNA-binding protein 43	gencc,clinvar
CD99L2	HGNC:18237	ENSG00000102181	Q8TCZ2	CD99 antigen-like protein 2	clinvar
GNE	HGNC:23657	ENSG00000159921	Q9Y223	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TARDBP	TAR DNA-binding protein 43	RNA-binding protein that is involved in various steps of RNA biogenesis and processing.
CD99L2	CD99 antigen-like protein 2	Plays a role in a late step of leukocyte extravasation helping cells to overcome the endothelial basement membrane.
GNE	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TARDBP	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
CD99L2	Other/Unknown	no		CD99L2
GNE	Enzyme (other)	yes	2.7.1.60	ROK, UDP_GlcNAc_Epimerase_2_dom, UDP-GlcNAc_Epase

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
secondary oocyte	1
ventricular zone	1
gastrocnemius	1
prefrontal cortex	1
right frontal lobe	1
colonic mucosa	1
mucosa of sigmoid colon	1
nasal cavity epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TARDBP	301	ubiquitous	marker	secondary oocyte, ventricular zone, ganglionic eminence
CD99L2	243	ubiquitous	marker	prefrontal cortex, gastrocnemius, right frontal lobe
GNE	286	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, nasal cavity epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TARDBP	7,245
GNE	2,210
CD99L2	1,241

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TARDBP	Q13148	44
GNE	Q9Y223	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CD99L2	Q8TCZ2	55.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective GNE causes sialuria, NK and IBM2	1	5710.0×	7e-04	GNE
Sialic acid metabolism	1	163.1×	0.012	GNE
Cell surface interactions at the vascular wall	1	47.6×	0.028	CD99L2
Hemostasis	1	18.0×	0.055	CD99L2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nuclear inner membrane organization	1	5617.3×	0.003	TARDBP
N-acetylglucosamine biosynthetic process	1	2808.7×	0.003	GNE
positive regulation of T cell extravasation	1	2808.7×	0.003	CD99L2
N-acetylneuraminate biosynthetic process	1	1872.4×	0.003	GNE
diapedesis	1	1123.5×	0.004	CD99L2
UDP-N-acetylglucosamine metabolic process	1	936.2×	0.004	GNE
CMP-N-acetylneuraminate biosynthetic process	1	936.2×	0.004	GNE
positive regulation of neutrophil extravasation	1	802.5×	0.004	CD99L2
host-mediated suppression of viral transcription	1	432.1×	0.007	TARDBP
3’-UTR-mediated mRNA destabilization	1	255.3×	0.010	TARDBP
3’-UTR-mediated mRNA stabilization	1	234.1×	0.010	TARDBP
amyloid fibril formation	1	200.6×	0.010	TARDBP
negative regulation of protein phosphorylation	1	193.7×	0.010	TARDBP
positive regulation of protein import into nucleus	1	140.4×	0.013	TARDBP
regulation of circadian rhythm	1	86.4×	0.018	TARDBP
positive regulation of insulin secretion	1	85.1×	0.018	TARDBP
rhythmic process	1	83.8×	0.018	TARDBP
response to endoplasmic reticulum stress	1	55.6×	0.026	TARDBP
regulation of protein stability	1	41.9×	0.032	TARDBP
RNA splicing	1	29.4×	0.042	TARDBP
regulation of gene expression	1	27.8×	0.042	TARDBP
regulation of apoptotic process	1	27.8×	0.042	TARDBP
mRNA processing	1	26.2×	0.043	TARDBP
regulation of cell cycle	1	24.9×	0.043	TARDBP
negative regulation of gene expression	1	23.0×	0.045	TARDBP
cell adhesion	1	12.5×	0.078	CD99L2

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

6 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Arimoclomol	Phase 3
Bimagrumab	Phase 3
Sirolimus	Phase 3
Alemtuzumab	Phase 2
Anakinra	Phase 2
Garetosmab	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
TARDBP	MITOXANTRONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TARDBP	1	4
CD99L2	0	0
GNE	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MITOXANTRONE	4	TARDBP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TARDBP	8	Binding:7, Functional:1
GNE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GNE	2.7.1.60, 3.2.1.183, 5.1.3.14	N-acylmannosamine kinase, UDP-N-acetylglucosamine 2-epimerase (hydrolysing), UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
MITOXANTRONE	4	TARDBP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TARDBP
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	GNE
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CD99L2

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CD99L2	0	—
GNE	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 73.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	32
PHASE1	15
PHASE2/PHASE3	8
PHASE2	8
EARLY_PHASE1	4
PHASE3	3
PHASE1/PHASE2	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT04789070	PHASE3	ACTIVE_NOT_RECRUITING	Phase III Trial of Sirolimus in IBM
NCT06450886	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Long-term Extension Study of Ulviprubart (ABC008) in Subjects With Inclusion Body Myositis
NCT07355257	PHASE2/PHASE3	NOT_YET_RECRUITING	TELITACICEPT IN INFLAMMATORY MYOPATHIES(TELITACICEPT-IM)
NCT00769860	PHASE2/PHASE3	COMPLETED	Arimoclomol in Sporadic Inclusion Body Myositis
NCT01165008	PHASE2/PHASE3	COMPLETED	Anakinra in Myositis
NCT01925209	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients
NCT02250443	PHASE2/PHASE3	COMPLETED	Study of Long-term Safety, Efficacy Tolerability of BYM338 in Patients With Sporadic Inclusion Body Myositis
NCT02481453	PHASE2/PHASE3	COMPLETED	Rapamycine vs Placebo for the Treatment of Inclusion Body Myositis
NCT02573467	PHASE3	COMPLETED	An Extension Study of the Efficacy, Safety and Tolerability of BYM338 (Bimagrumab) in Patients With Sporadic Inclusion Body Myositis Who Previously Participated in the Core Study CBYM338B2203
NCT04049097	PHASE3	TERMINATED	Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial
NCT05721573	PHASE2/PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of ABC008 for Inclusion Body Myositis
NCT06794008	PHASE2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT06821659	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of Universal CAR-T Cells (UWD-CD19) Combined with Immunosuppressants in the Treatment of Refractory Autoimmune Diseases
NCT06828042	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of Universal CD19-targeting CAR-γδT Cells in Refractory Autoimmune Diseases
NCT00001261	PHASE2	COMPLETED	Intravenousimmunoglobulin (IVIg) for the Treatment of Inflammatory Myopathies
NCT01423110	PHASE2	COMPLETED	Efficacy, Safety and Tolerability of BYM338 in Patients With Sporadic Inclusion Body Myositis
NCT02753530	PHASE2	COMPLETED	Study of Arimoclomol in Inclusion Body Myositis (IBM)
NCT03710941	PHASE2	WITHDRAWN	Safety and Efficacy of REGN2477+REGN1033 in Patients With Sporadic Inclusion Body Myositis
NCT04062019	PHASE2	UNKNOWN	Low-dose Interleukin-2 Treatment on Idiopathic Inflammatory Myopathy
NCT04237987	PHASE2	UNKNOWN	Low-dose Interleukin-2 in Combination With Standard Therapy on Idiopathic Inflammatory Myopathy
NCT04687111	PHASE2	UNKNOWN	Personalised Prospective Comparison of ARni With ArB in Patients With Natriuretic Peptide eLEvation
NCT06941129	PHASE1	RECRUITING	CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapse/Refractory Autoimmune Diseases
NCT06978647	PHASE1	RECRUITING	A Clinical Study of YTS109 Cell in R/R Autoimmune Diseases
NCT06978738	PHASE1	NOT_YET_RECRUITING	UCAR T-cell Therapy Targeting CD19/ BCMA in Patients With Relapse/ Refractory Autoimmune Diseases
NCT07104721	PHASE1	RECRUITING	A Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
NCT07123519	PHASE1	RECRUITING	A Clinical Study of YTS109 Cells for the Treatment of R/R Autoimmune Diseases
NCT07236762	PHASE1	RECRUITING	An Exploratory Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
NCT07236801	PHASE1	RECRUITING	Exploratory Clinical Study on YTS109 Cell Therapy for Autoimmune Diseases
NCT07413341	PHASE1	RECRUITING	A Clinical Study of TI-0032-III Injection in Patients With Relapsed and Refractory Autoimmune Diseases
NCT01519349	PHASE1	COMPLETED	Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis
NCT02483845	PHASE1	UNKNOWN	Natalizumab in Inclusion Body Myositis (IBM)
NCT03440034	PHASE1	COMPLETED	Study of Pioglitazone in Sporadic Inclusion Body Myositis
NCT04421677	PHASE1	COMPLETED	Safety and Tolerability of Phenylbutyrate in Inclusion Body Myositis
NCT04659031	PHASE1	COMPLETED	A Phase 1 Study of ABC008 in Ascending (Single Ascending Dose/Multiple Ascending Dose) Study in Patients With (IBM)
NCT05032131	PHASE1	UNKNOWN	Cell Therapy for IBM by Muscle Injection of ADSVF
NCT06524687	PHASE1	TERMINATED	A Study of Imvotamab in Active, Refractory Idiopathic Inflammatory Myopathies
NCT06420154	EARLY_PHASE1	NOT_YET_RECRUITING	The Safety and Efficacy of Anti-CD19 CAR-T Cells in Patients With Relapsed/Refractory Autoimmune Diseases
NCT06479863	EARLY_PHASE1	RECRUITING	Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Sporadic Inclusion Body Myositis
NCT00802815	EARLY_PHASE1	COMPLETED	Double-blind, Randomized, Placebo-controlled Trial of Etanercept for 12 Months in Subjects With Inclusion Body Myositis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ARIMOCLOMOL	4	3
ANAKINRA	4	1
NATALIZUMAB	4	1
OXYGEN	4	1
PHENYLBUTANOIC ACID	4	1
POZELIMAB	4	1
BIMAGRUMAB	3	4
CEMDISIRAN	3	1
GARETOSMAB	3	1
TELITACICEPT	3	1
YELLOW FEVER VACCINE	3	1
ULVIPRUBART	2	3
IMVOTAMAB	2	1
TREVOGRUMAB	2	1
CHEMBL4760607	0	3
CHEMBL5220618	0	1