Myocarditis

Summary

Myocarditis (MONDO:0004496) is a disease (an umbrella term covering 7 Mondo subtypes) with 15 cohort genes (5 GWAS associations across 5 studies) and 106 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (3 cohort genes). Top therapeutic interventions include muromonab-cd3, abatacept, and azathioprine.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 15
• GWAS associations: 5
• ClinVar variants: 12
• Clinical trials: 106

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myocarditis
Mondo ID	MONDO:0004496
EFO	EFO:0009609
MeSH	D009205
DOID	DOID:820
ICD-10-CM	I40
ICD-11	1018829714
NCIT	C34831
SNOMED CT	50920009
UMLS	C0027059
MedGen	44553
GARD	0007137
NORD	1882
Is cancer (heuristic)	no

Also known as: inflammation of myocardium · myocardial inflammation (finding) · myocardium inflammation

Data availability: 12 ClinVar variants · 5 GWAS associations (5 studies) · 1 cell line.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › myocarditis

Related subtypes (5): dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction

Subtypes (7): Fiedler’s myocarditis, bacterial myocarditis, acute myocarditis, interstitial myocarditis, rheumatic myocarditis, autoimmune myocarditis, viral myocarditis

Genetics & variants

GWAS landscape

5 GWAS associations across 5 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1012797842	1e-08	BCLAF1P2 - CCNYL1B	?
rs74675399	1e-07	GNA15-DT, GNA15	A	6.36
rs117188076	3e-07	ADAM7-AS1	T	13.74
rs2959223	4e-07	SIX2 - LINC01121	A	5.55
rs9463787	8e-07	EFHC1	G	7.67

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90018882	Sakaue S	2021	633	427,278	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90651491	Liu TY	2025	161	235,604	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90436090	Zhou W	2018	106	405,779	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90018662	Sakaue S	2021	102	177,745	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST009817	Lacaze P	2020	33	0	Genetic associations with clozapine-induced myocarditis in patients with schizophrenia.

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)	3
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	3
intergenic_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1012797842	16	34272123	G>A,C,T		intergenic_variant	BCLAF1P2 - CCNYL1B	1e-08	Tier 4: intronic/intergenic
rs74675399	19	3148871	G>A	0.07	non_coding_transcript_exon_variant	GNA15-DT, GNA15	1e-07	Tier 4: intronic/intergenic
rs117188076	8	24543885	C>T	0.03	intron_variant	ADAM7-AS1	3e-07	Tier 4: intronic/intergenic
rs2959223	2	45018026	G>A	0.3	intron_variant	SIX2 - LINC01121	4e-07	Tier 4: intronic/intergenic
rs9463787	6	52431785	A>G	0.13	intron_variant	EFHC1	8e-07	Tier 4: intronic/intergenic

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 3 likely pathogenic, 2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1675064	NM_004281.4(BAG3):c.612del (p.Tyr205fs)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228322	NM_004281.4(BAG3):c.925C>T (p.Arg309Ter)	BAG3	Pathogenic	criteria provided, multiple submitters, no conflicts
534283	NM_004415.4(DSP):c.4372C>T (p.Arg1458Ter)	DSP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
635051	NM_001267550.2(TTN):c.29621_29624del (p.Glu9874fs)	TTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1675070	NM_004415.4(DSP):c.2200del (p.Arg734fs)	DSP	Likely pathogenic	criteria provided, single submitter
837897	NM_000257.4(MYH7):c.644C>T (p.Thr215Ile)	MYH7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
523312	NM_000033.4(ABCD1):c.1866-1G>C	PLXNB3-AS1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
48090	NM_170707.4(LMNA):c.868G>A (p.Glu290Lys)	LMNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179447	NM_000363.5(TNNI3):c.204del (p.Arg69fs)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
132943	NM_001276345.2(TNNT2):c.460C>T (p.Arg154Trp)	TNNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523561	NM_152424.4(AMER1):c.1911_1912del (p.Glu637fs)	AMER1	Uncertain significance	criteria provided, single submitter
13454	NM_000371.4(TTR):c.386C>T (p.Ala129Val)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 73 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SIX2	Orphanet:488437	SIX2-related frontonasal dysplasia
SIX3	Orphanet:220386	Semilobar holoprosencephaly
SIX3	Orphanet:280195	Septopreoptic holoprosencephaly
SIX3	Orphanet:280200	Microform holoprosencephaly
SIX3	Orphanet:485275	Acquired schizencephaly
SIX3	Orphanet:93924	Lobar holoprosencephaly
SIX3	Orphanet:93925	Alobar holoprosencephaly
SIX3	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
TNNI3	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNI3	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TNNT2	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNT2	Orphanet:54260	Left ventricular noncompaction
TNNT2	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
TTR	Orphanet:597939	Euthyroid dysprealbuminemic hyperthyroxinemia
TTR	Orphanet:85447	ATTRV30M amyloidosis
TTR	Orphanet:85451	ATTRV122I amyloidosis
EFHC1	Orphanet:1941	Juvenile absence epilepsy
EFHC1	Orphanet:307	Juvenile myoclonic epilepsy
AMER1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
DSP	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:158687	Lethal acantholytic erosive disorder
DSP	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome
DSP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSP	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSP	Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome
DSP	Orphanet:50942	Striate palmoplantar keratoderma
DSP	Orphanet:65282	Carvajal syndrome
LMNA	Orphanet:154	Familial isolated dilated cardiomyopathy
LMNA	Orphanet:157973	Congenital muscular dystrophy due to LMNA mutation
LMNA	Orphanet:1662	Restrictive dermopathy
LMNA	Orphanet:168796	Heart-hand syndrome, Slovenian type
LMNA	Orphanet:2229	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome
LMNA	Orphanet:2348	Familial partial lipodystrophy, Dunnigan type
LMNA	Orphanet:280365	Autosomal semi-dominant severe lipodystrophic laminopathy

Cohort genes → proteins

15 cohort genes, 14 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	5
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SIX2	HGNC:10888	ENSG00000170577	Q9NPC8	Homeobox protein SIX2	gwas
SIX3	HGNC:10889	ENSG00000138083	O95343	Homeobox protein SIX3	gwas
TNNI3	HGNC:11947	ENSG00000129991	P19429	Troponin I, cardiac muscle	clinvar
TNNT2	HGNC:11949	ENSG00000118194	P45379	Troponin T, cardiac muscle	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
TTR	HGNC:12405	ENSG00000118271	P02766	Transthyretin	clinvar
EFHC1	HGNC:16406	ENSG00000096093	Q5JVL4	EF-hand domain-containing protein 1	gwas
ADAM7	HGNC:214	ENSG00000069206	Q9H2U9	Disintegrin and metalloproteinase domain-containing protein 7	gwas
AMER1	HGNC:26837	ENSG00000184675	Q5JTC6	APC membrane recruitment protein 1	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	clinvar
PLXNB3-AS1	HGNC:40454	ENSG00000232725		PLXNB3 antisense RNA 1	clinvar
GNA15	HGNC:4383	ENSG00000060558	P30679	Guanine nucleotide-binding protein subunit alpha-15	gwas
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar
BAG3	HGNC:939	ENSG00000151929	O95817	BAG family molecular chaperone regulator 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SIX2	Homeobox protein SIX2	Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach.
SIX3	Homeobox protein SIX3	Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes.
TNNI3	Troponin I, cardiac muscle	Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TNNT2	Troponin T, cardiac muscle	Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
TTR	Transthyretin	Thyroid hormone-binding protein.
EFHC1	EF-hand domain-containing protein 1	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
ADAM7	Disintegrin and metalloproteinase domain-containing protein 7	Required for normal male fertility via maintenance of epithelial cell morphology in the caput epididymis and subsequently correct epididymis lumen structure required for sperm development.
AMER1	APC membrane recruitment protein 1	Regulator of the canonical Wnt signaling pathway.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
GNA15	Guanine nucleotide-binding protein subunit alpha-15	Member of the G-protein alpha subunit family that plays a crucial role in intracellular signaling.
LMNA	Prelamin-A/C	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
BAG3	BAG family molecular chaperone regulator 3	Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g.

Protein-family classification

Druggable: 3 · Difficult: 5 · Unknown: 7 · Druggable fraction: 0.2

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
Scaffold/PPI	3	3.5×	0.313
Protease	1	2.4×	0.835
Kinase	1	1.9×	0.835
Transcription factor	2	1.1×	0.835
Other/Unknown	7	0.8×	0.835
Enzyme (other)	1	0.8×	0.835

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SIX2	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
SIX3	Transcription factor	no		HD, Homeodomain-like_sf, SIX1_SD
TNNI3	Other/Unknown	no		Troponin, Troponin-I_N, Troponin_sf
TNNT2	Other/Unknown	no		Troponin, TNNT, Troponin_sf
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
TTR	Other/Unknown	no		Transthyretin/HIU_hydrolase, Transthyretin/HIU_hydrolase_d, Thyroxine_BS
EFHC1	Other/Unknown	no		EF_hand_dom, DM10_dom, EF-hand-dom_pair
ADAM7	Protease	yes		Peptidase_M12B, Disintegrin_dom, Peptidase_M12B_N
AMER1	Other/Unknown	no		AMER
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
PLXNB3-AS1	Other/Unknown	no
GNA15	Enzyme (other)	yes	3.6.5.1	Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
BAG3	Scaffold/PPI	no		WW_dom, BAG_domain, WW_dom_sf

Expression context

Cohort genes with no expression data: 0.

13 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)	15
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	3
gastrocnemius	2
right atrium auricular region	2
skeletal muscle tissue of biceps brachii	2
skeletal muscle tissue of rectus abdominis	2
olfactory segment of nasal mucosa	1
parotid gland	1
nasal cavity epithelium	1
pigmented layer of retina	1
retina	1
left ventricle myocardium	1
cardiac atrium	1
biceps brachii	1
gluteal muscle	1
choroid plexus epithelium	1
right lobe of liver	1
type B pancreatic cell	1
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SIX2	156	broad	marker	olfactory segment of nasal mucosa, gastrocnemius, parotid gland
SIX3	92	broad	marker	pigmented layer of retina, retina, nasal cavity epithelium
TNNI3	169	broad	marker	apex of heart, left ventricle myocardium, right atrium auricular region
TNNT2	154	broad	marker	apex of heart, right atrium auricular region, cardiac atrium
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
TTR	185	broad	marker	choroid plexus epithelium, type B pancreatic cell, right lobe of liver
EFHC1	272	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
ADAM7	21	tissue_specific	marker	corpus epididymis, cauda epididymis, epididymis
AMER1	156	ubiquitous	yes	cortical plate, skeletal muscle tissue of rectus abdominis, myocardium
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
PLXNB3-AS1	133		yes	sural nerve, primordial germ cell in gonad, muscle layer of sigmoid colon
GNA15	218	broad	marker	lower esophagus mucosa, esophagus squamous epithelium, esophagus mucosa
LMNA	295	ubiquitous	marker	nipple, mucosa of stomach, skin of abdomen
MYH7	167	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii
BAG3	286	ubiquitous	marker	gastrocnemius, skeletal muscle tissue of rectus abdominis, body of tongue

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNA	7,173
BAG3	4,957
TTR	4,528
TTN	4,237
DSP	2,897
MYH7	2,744
EFHC1	2,470
TNNT2	1,944
TNNI3	1,836
SIX3	1,536

Intra-cohort edges

A	B	Sources
MYH7	TNNI3	string_interaction
MYH7	TNNT2	string_interaction
MYH7	TTN	string_interaction
TNNI3	TNNT2	biogrid_interaction, string_interaction
TNNI3	TTN	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 5 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTR	P02766	462
TTN	Q8WZ42	64
MYH7	P12883	43
TNNI3	P19429	39
LMNA	P02545	28
TNNT2	P45379	25
DSP	P15924	4
AMER1	Q5JTC6	3
EFHC1	Q5JVL4	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNA15	P30679	90.74
SIX2	Q9NPC8	75.99
ADAM7	Q9H2U9	75.03
SIX3	O95343	70.38
BAG3	O95817	57.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 68. Enrichment computed across 15 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Striated Muscle Contraction	3	92.6×	3e-04	TNNI3, TNNT2, TTN
Deletions in the AMER1 gene destabilize the destruction complex	1	1142.0×	0.030	AMER1
Breakdown of the nuclear lamina	1	380.7×	0.036	LMNA
Defective visual phototransduction due to STRA6 loss of function	1	380.7×	0.036	TTR
Cellular responses to stress	3	11.1×	0.036	AMER1, LMNA, BAG3
Cellular responses to stimuli	3	9.4×	0.037	AMER1, LMNA, BAG3
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	142.8×	0.037	GNA15
Acetylcholine regulates insulin secretion	1	114.2×	0.037	GNA15
Apoptotic cleavage of cell adhesion proteins	1	103.8×	0.037	DSP
Signaling by AXIN mutants	1	103.8×	0.037	AMER1
Signaling by CTNNB1 phospho-site mutants	1	103.8×	0.037	AMER1
Signaling by APC mutants	1	103.8×	0.037	AMER1
Signaling by AMER1 mutants	1	103.8×	0.037	AMER1
APC truncation mutants have impaired AXIN binding	1	81.6×	0.037	AMER1
AXIN missense mutants destabilize the destruction complex	1	81.6×	0.037	AMER1
Truncations of AMER1 destabilize the destruction complex	1	81.6×	0.037	AMER1
Kidney development	1	81.6×	0.037	SIX2
Depolymerization of the Nuclear Lamina	1	76.1×	0.037	LMNA
Signaling by GSK3beta mutants	1	76.1×	0.037	AMER1
CTNNB1 S33 mutants aren’t phosphorylated	1	76.1×	0.037	AMER1
CTNNB1 S37 mutants aren’t phosphorylated	1	76.1×	0.037	AMER1
CTNNB1 S45 mutants aren’t phosphorylated	1	76.1×	0.037	AMER1
CTNNB1 T41 mutants aren’t phosphorylated	1	76.1×	0.037	AMER1
Diseases of signal transduction by growth factor receptors and second messengers	2	11.4×	0.037	AMER1, LMNA
Beta-catenin phosphorylation cascade	1	67.2×	0.040	AMER1
Initiation of Nuclear Envelope (NE) Reformation	1	60.1×	0.042	LMNA
Signaling by WNT in cancer	1	60.1×	0.042	AMER1
The canonical retinoid cycle in rods (twilight vision)	1	51.9×	0.042	TTR
IRE1alpha activates chaperones	1	51.9×	0.042	LMNA
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	51.9×	0.042	LMNA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
muscle filament sliding	4	300.9×	1e-07	TNNI3, TNNT2, TTN, MYH7
cardiac muscle contraction	4	114.6×	3e-06	TNNI3, TNNT2, TTN, MYH7
mesenchymal cell differentiation involved in kidney development	2	1203.7×	4e-05	SIX2, AMER1
ventricular cardiac muscle tissue morphogenesis	3	150.5×	4e-05	TNNI3, TNNT2, MYH7
skeletal muscle contraction	3	109.4×	9e-05	TNNI3, TTN, MYH7
negative regulation of ATP-dependent activity	2	240.7×	9e-04	TNNI3, TNNT2
striated muscle contraction	2	120.4×	0.003	TTN, MYH7
protein import into nucleus	3	30.9×	0.003	SIX2, SIX3, LMNA
proximal/distal axis specification	1	1203.7×	0.011	SIX3
striated muscle cell apoptotic process	1	1203.7×	0.011	BAG3
nephron morphogenesis	1	1203.7×	0.011	SIX2
regulation of branching involved in ureteric bud morphogenesis	1	1203.7×	0.011	SIX2
sarcomere organization	2	54.7×	0.011	TNNT2, TTN
response to calcium ion	2	45.4×	0.011	TNNT2, TTN
regulation of systemic arterial blood pressure by ischemic conditions	1	601.9×	0.014	TNNI3
optic vesicle morphogenesis	1	601.9×	0.014	SIX3
regulation of slow-twitch skeletal muscle fiber contraction	1	601.9×	0.014	MYH7
mesenchymal stem cell maintenance involved in nephron morphogenesis	1	601.9×	0.014	SIX2
mesenchymal stem cell proliferation	1	601.9×	0.014	SIX2
positive regulation of sperm capacitation	1	601.9×	0.014	ADAM7
epididymis development	1	601.9×	0.014	ADAM7
negative regulation of striated muscle cell apoptotic process	1	401.2×	0.015	BAG3
regulation of the force of skeletal muscle contraction	1	401.2×	0.015	MYH7
skeletal muscle myosin thick filament assembly	1	401.2×	0.015	TTN
sarcomerogenesis	1	401.2×	0.015	TTN
regulation of neural retina development	1	401.2×	0.015	SIX3
condensed mesenchymal cell proliferation	1	401.2×	0.015	SIX2
protein transport along microtubule	1	401.2×	0.015	BAG3
DNA double-strand break attachment to nuclear envelope	1	401.2×	0.015	LMNA
muscle contraction	2	29.7×	0.015	TTN, MYH7

Therapeutics

Drugs indicated for this disease

3 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dexamethasone	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Methylprednisolone	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

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

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 12

Druggability breadth: 9 of 15 evidence-associated genes (60%) 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
TTR	TRICLABENDAZOLE
LMNA	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
TTR	29	4
GNA15	2	3
SIX2	0	0
SIX3	0	0
TNNI3	0	0
TNNT2	0	0
TTN	0	0
EFHC1	0	0
ADAM7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRICLABENDAZOLE	4	TTR
AMLEXANOX	4	TTR
TOLCAPONE	4	TTR
DICLOFENAC	4	TTR
LEVOTHYROXINE	4	LMNA, TTR
TAFAMIDIS	4	TTR
BENZIODARONE	4	LMNA, TTR
BITHIONOL	4	LMNA, TTR
BENZBROMARONE	4	LMNA, TTR
ACORAMIDIS	4	TTR
GEMFIBROZIL	4	TTR
MECLOFENAMIC ACID	4	TTR
DASATINIB	4	TTR
DEXTROTHYROXINE	4	LMNA, TTR
TRICLOSAN	4	LMNA, TTR
DIFLUNISAL	4	LMNA, TTR
BEPRIDIL	4	LMNA
PHENYLBUTAZONE	4	LMNA
CEFOTAXIME SODIUM	4	LMNA
DIENESTROL	4	LMNA
IFOSFAMIDE	4	LMNA
PROGESTERONE	4	LMNA
CLOTRIMAZOLE	4	LMNA
DAPSONE	4	LMNA
AMINOCAPROIC ACID	4	LMNA
FLUCONAZOLE	4	LMNA
COLCHICINE	4	LMNA
NABUMETONE	4	LMNA
OXAPROZIN	4	LMNA
BUMETANIDE	4	LMNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TTR	423	Binding:391, Functional:32
LMNA	12	Binding:9, Functional:3
BAG3	8	Binding:8
GNA15	3	Binding:2, Functional:1
TNNI3	2	Binding:2
TNNT2	2	Binding:2
DSP	2	Binding:2
TTN	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase
GNA15	3.6.5.1	heterotrimeric G-protein GTPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TTR	423

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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)
TRICLABENDAZOLE	4	TTR
AMLEXANOX	4	TTR
TOLCAPONE	4	TTR
DICLOFENAC	4	TTR
LEVOTHYROXINE	4	LMNA, TTR
TAFAMIDIS	4	TTR
BENZIODARONE	4	LMNA, TTR
BITHIONOL	4	LMNA, TTR
BENZBROMARONE	4	LMNA, TTR
ACORAMIDIS	4	TTR
GEMFIBROZIL	4	TTR
MECLOFENAMIC ACID	4	TTR
DASATINIB	4	TTR
DEXTROTHYROXINE	4	LMNA, TTR
TRICLOSAN	4	LMNA, TTR
DIFLUNISAL	4	LMNA, TTR
BEPRIDIL	4	LMNA
PHENYLBUTAZONE	4	LMNA
CEFOTAXIME SODIUM	4	LMNA
DIENESTROL	4	LMNA
IFOSFAMIDE	4	LMNA
PROGESTERONE	4	LMNA
CLOTRIMAZOLE	4	LMNA
DAPSONE	4	LMNA
AMINOCAPROIC ACID	4	LMNA
FLUCONAZOLE	4	LMNA
COLCHICINE	4	LMNA
NABUMETONE	4	LMNA
OXAPROZIN	4	LMNA
BUMETANIDE	4	LMNA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TTR, LMNA
B	Phased (≥1) drug, not yet approved	1	GNA15
C	Druggable family + PDB, no drug	1	TTN
D	Druggable family + AlphaFold only, no drug	1	ADAM7
E	Difficult family or no structure, no drug	10	SIX2, SIX3, TNNI3, TNNT2, EFHC1, AMER1, DSP, PLXNB3-AS1, MYH7, BAG3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SIX2	0	—
SIX3	0	—
TNNI3	2	—
TNNT2	2	—
TTN	1	—
EFHC1	0	—
ADAM7	0	—
AMER1	0	—
DSP	2	—
PLXNB3-AS1	0	—
MYH7	0	—
BAG3	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 106.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	93
PHASE3	4
PHASE2	4
PHASE4	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04654988	PHASE4	RECRUITING	Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy.
NCT05295290	PHASE4	ACTIVE_NOT_RECRUITING	A Study to Learn About The COVID-19 (Study) Vaccine (Called COMIRNATY) in People That Are Less Than 21 Years Old.
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT05150704	PHASE3	RECRUITING	MYTHS - MYocarditis THerapy With Steroids
NCT05335928	PHASE3	RECRUITING	Abatacept in Immune Checkpoint Inhibitor Myocarditis
NCT05961202	PHASE2/PHASE3	RECRUITING	The Effects of Hydroxychloroquine in Patients with Inflammatory Cardiomyopathy
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06686862	PHASE3	RECRUITING	Non-Steroidal Anti-Inflammatory Drugs in Acute Myocarditis
NCT02319278	PHASE2/PHASE3	COMPLETED	DEtection of Cellular Inflammation With FERumoxytol in the HEART
NCT05195645	PHASE2	ACTIVE_NOT_RECRUITING	AbataCept for the Treatment of Immune-cHeckpoint Inhibitors Induced mYocarditiS
NCT06896253	PHASE2	NOT_YET_RECRUITING	Pulse Corticosteroids Or/and Immunoglobulins to Treat Fulminant Myocarditis
NCT00000524	PHASE2	COMPLETED	Myocarditis Treatment Trial
NCT00004482	PHASE2	COMPLETED	Phase II Randomized Study of Muromonab-CD3, Cyclosporine, Methylprednisolone, and Prednisone in Patients With Giant Cell Myocarditis
NCT03049254	Not specified	RECRUITING	Mayo AVC Registry and Biobank
NCT03527342	Not specified	ENROLLING_BY_INVITATION	Sahlgrenska Cardiomyopathy Project
NCT03842592	Not specified	ACTIVE_NOT_RECRUITING	Ventricular Arrhythmia After Myocarditis in Sportsman
NCT04444128	Not specified	RECRUITING	IMPRoving Cardiovascular RiSk Stratification Using T1 Mapping in General populatION
NCT04464655	Not specified	RECRUITING	A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
NCT04521790	Not specified	RECRUITING	Role of Endomyocardial Biopsy and Aetiology-based Treatment in Patients With Inflammatory Heart Disease in Arrhythmic and Non-arrhythmic Clinical Presentations: an Integrated Approach for the Optimal Diagnostic and Therapeutic Management
NCT04612296	Not specified	RECRUITING	The Heart Hive - Cardiomyopathy Study
NCT04774549	Not specified	ACTIVE_NOT_RECRUITING	Inflammatory Cardiomyopathy Bern Registry
NCT04844151	Not specified	RECRUITING	Acute Myocarditis Registry With Prognostic, Histologic, Immunologic, Biological, Imaging and Clinical Assessment
NCT04967807	Not specified	ACTIVE_NOT_RECRUITING	Myocardial Injury and Outcomes Following COVID-19 Vaccination (MYOVAX Study)
NCT05046002	Not specified	RECRUITING	COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry
NCT05125965	Not specified	ACTIVE_NOT_RECRUITING	Contribution of Cardiac MRI in the Early Diagnosis of Myocarditis Induced by Immunotherapy
NCT05139329	Not specified	NOT_YET_RECRUITING	The ORCHESTRATE-Myocarditis Registry
NCT05158751	Not specified	NOT_YET_RECRUITING	Myocarditis Causing Premature Ventricular Contractions:Insights From the MAVERIC Registry
NCT05610423	Not specified	ENROLLING_BY_INVITATION	Covid-19 Vaccine Associated Myocarditis and Pericarditis in Norway
NCT05949450	Not specified	NOT_YET_RECRUITING	Prognostic Role of High Sensitivity Troponin During Follow up in the Evolution of Acute Myocarditis
NCT06001073	Not specified	RECRUITING	Prognosis Prediction System of Patients With Cardiovascular and Cerebrovascular Diseases Based on Multi-omics
NCT06010199	Not specified	RECRUITING	Risk Stratification Value of Biomarkers in Patients With Myocarditis
NCT06060548	Not specified	RECRUITING	Role of Novel ILR in the Management of PVCs
NCT06189053	Not specified	ACTIVE_NOT_RECRUITING	A Study to Assess Long-term Outcomes of Myocarditis Following Administration of COVID-19 mRNA Vaccine (SPIKEVAX)
NCT06409585	Not specified	RECRUITING	Cardiomyopathies and Heart Muscle Diseases: Cardiac Imaging in the Evaluation of Myocardial Fibrosis Transition
NCT06411340	Not specified	NOT_YET_RECRUITING	Inflammation in Acute Cardiovascular Diseases - the CArdiovascular Inflammation Registry (CAIR)
NCT06591260	Not specified	RECRUITING	Role of Endomyocardial Biopsy and Aetiology-based Treatment in Pediatric Patients with Inflammatory Heart Disease in Arrhythmic and Non-arrhythmic Clinical Presentations: an Integrated Approach for the Optimal Diagnostic and Therapeutic Management (MYOPED)
NCT06652399	Not specified	ENROLLING_BY_INVITATION	Cardiovascular Imaging in Pediatric Myocarditis
NCT06730607	Not specified	RECRUITING	Image-Based Prediction of Ventricular Tachycardias in Post-Myocarditis Patients: an International Multicenter Case-control Study
NCT06748261	Not specified	NOT_YET_RECRUITING	AI-enabled Screening and Diagnosis of Cardiomyopathies Using Coronary CTA
NCT06804278	Not specified	RECRUITING	Role of Spectral CT in the Diagnosis of Myocarditis/MINOCA in Patients Undergoing cardioCT Investigations for Acute Chest Pain

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MUROMONAB-CD3	4	2
ABATACEPT	4	1
AZATHIOPRINE	4	1
FERUMOXYTOL	4	1
IVABRADINE	4	1
INTERLEUKIN-10	2	1
CHEMBL454299	0	1
CHEMBL2368770	0	1
TNF-ALPHA	0	1