Malignant hyperthermia of anesthesia

Summary

Malignant hyperthermia of anesthesia (MONDO:0018493) is a disease with 4 cohort genes and 9 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 4
• ClinVar variants: 196
• Phenotypes (HPO): 23
• Clinical trials: 9

Clinical features

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0001942	Metabolic acidosis	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0002047	Malignant hyperthermia	Frequent (30-79%)
HP:0002789	Tachypnea	Frequent (30-79%)
HP:0002905	Hyperphosphatemia	Frequent (30-79%)
HP:0003552	Muscle stiffness	Frequent (30-79%)
HP:0004755	Supraventricular tachycardia	Frequent (30-79%)
HP:0004756	Ventricular tachycardia	Frequent (30-79%)
HP:0011964	Intermittent painful muscle spasms	Frequent (30-79%)
HP:0012416	Hypercapnia	Frequent (30-79%)
HP:0031320	Cardiomyocyte mitochondrial proliferation	Frequent (30-79%)
HP:0001722	High-output congestive heart failure	Occasional (5-29%)
HP:0001919	Acute kidney injury	Occasional (5-29%)
HP:0002153	Hyperkalemia	Occasional (5-29%)
HP:0002913	Myoglobinuria	Occasional (5-29%)
HP:0003256	Abnormality of the coagulation cascade	Occasional (5-29%)
HP:0006554	Acute hepatic failure	Occasional (5-29%)
HP:0006682	Ventricular extrasystoles	Occasional (5-29%)
HP:0008331	Elevated creatine kinase after exercise	Occasional (5-29%)
HP:0008942	Acute rhabdomyolysis	Occasional (5-29%)
HP:0008978	Necrotizing myopathy	Occasional (5-29%)
HP:0009045	Exercise-induced rhabdomyolysis	Occasional (5-29%)
HP:3000005	Abnormality of masseter muscle	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	malignant hyperthermia of anesthesia
Mondo ID	MONDO:0018493
MeSH	D008305
Orphanet	423
DOID	DOID:8545
NCIT	C84869
SNOMED CT	405501007
UMLS	C0024591
MedGen	9867
GARD	0006964
MedDRA	10020844
Is cancer (heuristic)	no

Also known as: anaesthesia related hyperthermia · hyperthermia of anaesthesia · hyperthermia of anesthesia · malignant hyperpyrexia · malignant hyperpyrexia due to anaesthesia · malignant hyperthermia · malignant hyperthermia of anesthesia · malignant hyperthermia syndrome

Data availability: 196 ClinVar variants · 128 ClinGen variant curations · 2 GenCC gene-disease records · 1 HPO phenotype · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neuromuscular disease › muscular channelopathy › malignant hyperthermia of anesthesia

Related subtypes (11): Andersen-Tawil syndrome, Morvan syndrome, Thomsen and Becker disease, Isaac syndrome, RYR1-related myopathy, CNGB3-related retinopathy, SCN4A-related channelopathy, neurological muscular channelopathy due to a genetic sodium channel defect, neurological muscular channelopathy due to a genetic chloride channel defect, neurological muscular channelopathy due to a genetic calcium channel defect, neurological muscular channelopathy due to a genetic potassium channel defect

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

196 retrieved; paginated sample, class counts are floors:

121 uncertain significance, 21 likely pathogenic, 12 pathogenic; drug response, 10 conflicting classifications of pathogenicity, 9 likely benign, 7 pathogenic, 4 benign, 3 drug response, 3 pathogenic/likely pathogenic, 2 likely pathogenic; drug response, 2 benign/likely benign, 1 conflicting classifications of pathogenicity; drug response, 1 vus-high

ClinVar	Variant (HGVS)	Gene	Classification	Review
1683485	NM_004318.4(ASPH):c.323-11779G>C	ASPH	Pathogenic	no assertion criteria provided
12964	NM_000540.3(RYR1):c.1840C>T (p.Arg614Cys)	RYR1	Pathogenic; drug response	reviewed by expert panel
12966	NM_000540.3(RYR1):c.7304G>A (p.Arg2435His)	RYR1	Pathogenic; drug response	reviewed by expert panel
12967	NM_000540.3(RYR1):c.487C>T (p.Arg163Cys)	RYR1	Pathogenic; drug response	reviewed by expert panel
12970	NM_000540.3(RYR1):c.7300G>A (p.Gly2434Arg)	RYR1	Pathogenic; drug response	reviewed by expert panel
12976	NM_000540.3(RYR1):c.6502G>A (p.Val2168Met)	RYR1	Pathogenic; drug response	reviewed by expert panel
12977	NM_000540.3(RYR1):c.6617C>T (p.Thr2206Met)	RYR1	Pathogenic	reviewed by expert panel
12992	NM_000540.3(RYR1):c.13909A>G (p.Thr4637Ala)	RYR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
133027	NM_000540.3(RYR1):c.11969G>T (p.Gly3990Val)	RYR1	Pathogenic; drug response	reviewed by expert panel
133029	NM_000540.3(RYR1):c.1201C>T (p.Arg401Cys)	RYR1	Pathogenic; drug response	reviewed by expert panel
133030	NM_000540.3(RYR1):c.1202G>A (p.Arg401His)	RYR1	Pathogenic	reviewed by expert panel
1330358	NM_000540.3(RYR1):c.7879G>C (p.Val2627Leu)	RYR1	Pathogenic	reviewed by expert panel
133040	NM_000540.3(RYR1):c.12700G>C (p.Val4234Leu)	RYR1	Pathogenic	reviewed by expert panel
133081	NM_000540.3(RYR1):c.14627A>G (p.Lys4876Arg)	RYR1	Pathogenic	reviewed by expert panel
133098	NM_000540.3(RYR1):c.14918C>T (p.Pro4973Leu)	RYR1	Pathogenic/Likely pathogenic	reviewed by expert panel
133102	NM_000540.3(RYR1):c.1597C>T (p.Arg533Cys)	RYR1	Pathogenic; drug response	reviewed by expert panel
133174	NM_000540.3(RYR1):c.7007G>A (p.Arg2336His)	RYR1	Pathogenic; drug response	reviewed by expert panel
133183	NM_000540.3(RYR1):c.7063C>T (p.Arg2355Trp)	RYR1	Pathogenic; drug response	reviewed by expert panel
133202	NM_000540.3(RYR1):c.7360C>T (p.Arg2454Cys)	RYR1	Pathogenic; drug response	reviewed by expert panel
133203	NM_000540.3(RYR1):c.742G>C (p.Gly248Arg)	RYR1	Pathogenic	reviewed by expert panel
65980	NM_000540.3(RYR1):c.7361G>A (p.Arg2454His)	RYR1	Pathogenic; drug response	reviewed by expert panel
929034	NM_000540.3(RYR1):c.2836G>T (p.Glu946Ter)	RYR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
156288	NM_000069.3(CACNA1S):c.3256C>A (p.Arg1086Ser)	CACNA1S	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071064	NM_000540.3(RYR1):c.12700G>T (p.Val4234Leu)	RYR1	Likely pathogenic	reviewed by expert panel
1210300	NM_000540.3(RYR1):c.3166G>C (p.Asp1056His)	RYR1	Likely pathogenic	reviewed by expert panel
1210316	NM_000540.3(RYR1):c.14803G>A (p.Gly4935Ser)	RYR1	Likely pathogenic	reviewed by expert panel
1210317	NM_000540.3(RYR1):c.1615T>G (p.Phe539Val)	RYR1	Likely pathogenic	reviewed by expert panel
12965	NM_000540.3(RYR1):c.742G>A (p.Gly248Arg)	RYR1	Likely pathogenic	reviewed by expert panel
12971	NM_000540.3(RYR1):c.7372C>T (p.Arg2458Cys)	RYR1	Likely pathogenic; drug response	reviewed by expert panel
133012	NM_000540.3(RYR1):c.11315G>A (p.Arg3772Gln)	RYR1	Likely pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 27 · Orphanet: 17 · 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
RYR1	Definitive	Autosomal dominant	malignant hyperthermia, susceptibility to, 1	22
ASPH	Moderate	Autosomal dominant	malignant hyperthermia of anesthesia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR1	Orphanet:169186	Autosomal recessive centronuclear myopathy
RYR1	Orphanet:169189	Autosomal dominant centronuclear myopathy
RYR1	Orphanet:178145	Moderate multiminicore disease with hand involvement
RYR1	Orphanet:324581	Benign Samaritan congenital myopathy
RYR1	Orphanet:33108	Lethal multiple pterygium syndrome
RYR1	Orphanet:423	Malignant hyperthermia of anesthesia
RYR1	Orphanet:424107	Congenital myopathy with myasthenic-like onset
RYR1	Orphanet:466650	Exercise-induced malignant hyperthermia
RYR1	Orphanet:597	Central core disease
RYR1	Orphanet:700188	Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1	Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia
RYR1	Orphanet:99741	King-Denborough syndrome
ASPH	Orphanet:412022	Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome
CACNA1S	Orphanet:397755	Periodic paralysis with transient compartment-like syndrome
CACNA1S	Orphanet:423	Malignant hyperthermia of anesthesia
CACNA1S	Orphanet:681	Hypokalemic periodic paralysis
CACNA1S	Orphanet:79102	Thyrotoxic periodic paralysis

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	gencc,clinvar
ASPH	HGNC:757	ENSG00000198363	Q12797	Aspartyl/asparaginyl beta-hydroxylase	gencc,clinvar
TRPV1	HGNC:12716	ENSG00000196689	Q8NER1	Transient receptor potential cation channel subfamily V member 1	clinvar
CACNA1S	HGNC:1397	ENSG00000081248	Q13698	Voltage-dependent L-type calcium channel subunit alpha-1S	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RYR1	Ryanodine receptor 1	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.
ASPH	Aspartyl/asparaginyl beta-hydroxylase	Specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.
TRPV1	Transient receptor potential cation channel subfamily V member 1	Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli.
CACNA1S	Voltage-dependent L-type calcium channel subunit alpha-1S	Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle.

Protein-family classification

Druggable: 4 · 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
Ion channel	3	83.7×	6e-06
Enzyme (other)	1	3.0×	0.294

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt
ASPH	Enzyme (other)	yes	1.14.11.16	Asp/Arg/Pro-Hydrxlase, Asp-B-hydro/Triadin_dom, TPR-like_helical_dom_sf
TRPV1	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4
CACNA1S	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1ssu

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gluteal muscle	2
hindlimb stylopod muscle	2
gastrocnemius	1
calcaneal tendon	1
palpebral conjunctiva	1
stromal cell of endometrium	1
right lobe of liver	1
sural nerve	1
tibial nerve	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle
ASPH	289	ubiquitous	marker	calcaneal tendon, stromal cell of endometrium, palpebral conjunctiva
TRPV1	189	tissue_specific	yes	right lobe of liver, sural nerve, tibial nerve
CACNA1S	105	tissue_specific	marker	gluteal muscle, hindlimb stylopod muscle, triceps brachii

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPV1	2,258
RYR1	2,177
ASPH	1,866
CACNA1S	1,818

Intra-cohort edges

A	B	Sources
ASPH	RYR1	string_interaction
CACNA1S	RYR1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASPH	Q12797	43
TRPV1	Q8NER1	13
RYR1	P21817	2
CACNA1S	Q13698	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ion homeostasis	2	102.0×	0.002	RYR1, ASPH
Stimuli-sensing channels	2	68.0×	0.003	RYR1, ASPH
Cardiac conduction	2	54.4×	0.003	RYR1, ASPH
Ion channel transport	2	48.0×	0.003	RYR1, ASPH
Muscle contraction	2	38.6×	0.003	RYR1, ASPH
Protein hydroxylation	1	135.9×	0.017	ASPH
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	105.7×	0.017	ASPH
TRP channels	1	102.0×	0.017	TRPV1
Transport of small molecules	2	12.6×	0.017	RYR1, ASPH
NCAM signaling for neurite out-growth	1	68.0×	0.023	CACNA1S
NCAM1 interactions	1	62.1×	0.023	CACNA1S
Axon guidance	1	11.3×	0.111	CACNA1S
Nervous system development	1	10.7×	0.111	CACNA1S
Post-translational protein modification	1	4.8×	0.220	ASPH
Developmental Biology	1	3.6×	0.266	CACNA1S
Metabolism of proteins	1	3.1×	0.286	ASPH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
calcium ion transmembrane transport	3	158.0×	1e-05	ASPH, TRPV1, CACNA1S
muscle contraction	3	156.0×	1e-05	RYR1, ASPH, CACNA1S
cellular response to caffeine	2	766.0×	5e-05	RYR1, CACNA1S
striated muscle contraction	2	421.3×	1e-04	RYR1, CACNA1S
skeletal muscle fiber development	2	271.8×	2e-04	RYR1, CACNA1S
calcium ion import across plasma membrane	2	271.8×	2e-04	TRPV1, CACNA1S
regulation of cytosolic calcium ion concentration	2	191.5×	4e-04	RYR1, ASPH
release of sequestered calcium ion into cytosol	2	172.0×	4e-04	RYR1, CACNA1S
protein homotetramerization	2	118.7×	7e-04	RYR1, TRPV1
cellular response to calcium ion	2	100.3×	9e-04	RYR1, ASPH
obsolete regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity	1	4213.0×	0.001	ASPH
skeletal muscle adaptation	1	4213.0×	0.001	CACNA1S
response to capsazepine	1	4213.0×	0.001	TRPV1
regulation of protein depolymerization	1	4213.0×	0.001	ASPH
calcium ion transport	2	90.6×	0.001	RYR1, CACNA1S
fever generation	1	1404.3×	0.003	TRPV1
detection of temperature stimulus involved in thermoception	1	1404.3×	0.003	TRPV1
peptide secretion	1	1053.2×	0.003	TRPV1
sensory perception of mechanical stimulus	1	1053.2×	0.003	TRPV1
thermoception	1	1053.2×	0.003	TRPV1
detection of chemical stimulus involved in sensory perception of pain	1	1053.2×	0.003	TRPV1
smooth muscle contraction involved in micturition	1	1053.2×	0.003	TRPV1
chemosensory behavior	1	842.6×	0.003	TRPV1
activation of store-operated calcium channel activity	1	842.6×	0.003	ASPH
cellular response to alkaloid	1	842.6×	0.003	TRPV1
extraocular skeletal muscle development	1	702.2×	0.004	CACNA1S
regulation of cell communication by electrical coupling	1	601.9×	0.004	ASPH
response to caffeine	1	601.9×	0.004	RYR1
positive regulation of muscle contraction	1	601.9×	0.004	CACNA1S
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	421.3×	0.005	RYR1

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 4 evidence-associated genes (100%) 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
ASPH	VEMURAFENIB
TRPV1	CANNABIDIOL
CACNA1S	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1S	48	4
TRPV1	19	4
ASPH	13	4
RYR1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	ASPH
ROXADUSTAT	4	ASPH
VENETOCLAX	4	ASPH
DAPRODUSTAT	4	ASPH
VADADUSTAT	4	ASPH
BELINOSTAT	4	ASPH
BLEOMYCIN	4	ASPH
MIDOSTAURIN	4	ASPH
CANNABIDIOL	4	TRPV1
CAPSAICIN	4	TRPV1
PROPOFOL	4	TRPV1
BEPRIDIL	4	CACNA1S
IMIPRAMINE	4	CACNA1S
HALOFANTRINE	4	CACNA1S
DROPERIDOL	4	CACNA1S
SAQUINAVIR	4	CACNA1S
DULOXETINE	4	CACNA1S
DIAZEPAM	4	CACNA1S
SERTINDOLE	4	CACNA1S
QUINIDINE	4	CACNA1S
LAMIVUDINE	4	CACNA1S
PIMOZIDE	4	CACNA1S
PHENYTOIN	4	CACNA1S
TERFENADINE	4	CACNA1S
CISAPRIDE	4	CACNA1S
SOLIFENACIN	4	CACNA1S
NIFEDIPINE	4	CACNA1S
DILTIAZEM	4	CACNA1S
NILOTINIB	4	CACNA1S
ASTEMIZOLE	4	CACNA1S

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TRPV1	674	Binding:506, Functional:166, ADMET:2
CACNA1S	228	Binding:142, Functional:79, Toxicity:5, ADMET:2
RYR1	16	Binding:13, Functional:3
ASPH	15	Binding:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ASPH	1.14.11.16	peptide-aspartate beta-dioxygenase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TRPV1	674
CACNA1S	228

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1
CACNA1S	1

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)
VEMURAFENIB	4	ASPH
ROXADUSTAT	4	ASPH
VENETOCLAX	4	ASPH
DAPRODUSTAT	4	ASPH
VADADUSTAT	4	ASPH
BELINOSTAT	4	ASPH
BLEOMYCIN	4	ASPH
MIDOSTAURIN	4	ASPH
CANNABIDIOL	4	TRPV1
CAPSAICIN	4	TRPV1
PROPOFOL	4	TRPV1
BEPRIDIL	4	CACNA1S
IMIPRAMINE	4	CACNA1S
HALOFANTRINE	4	CACNA1S
DROPERIDOL	4	CACNA1S
SAQUINAVIR	4	CACNA1S
DULOXETINE	4	CACNA1S
DIAZEPAM	4	CACNA1S
SERTINDOLE	4	CACNA1S
QUINIDINE	4	CACNA1S
LAMIVUDINE	4	CACNA1S
PIMOZIDE	4	CACNA1S
PHENYTOIN	4	CACNA1S
TERFENADINE	4	CACNA1S
CISAPRIDE	4	CACNA1S
SOLIFENACIN	4	CACNA1S
NIFEDIPINE	4	CACNA1S
DILTIAZEM	4	CACNA1S
NILOTINIB	4	CACNA1S
ASTEMIZOLE	4	CACNA1S

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ASPH, TRPV1, CACNA1S
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	RYR1
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)
RYR1	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05402839	Not specified	RECRUITING	Screening of Malignant Hyperthermia Susceptible Individuals
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT01624558	Not specified	WITHDRAWN	Effectiveness of Carbon Filters to Reduce the Anesthetic Gas Concentration in an Anesthetized Patient
NCT02561598	Not specified	WITHDRAWN	A Case Control Study of Patients With Diagnosis of Malignant Hyperthermia
NCT02964481	Not specified	TERMINATED	Malignant Hyperthermia Registry and Genetic Testing
NCT03964870	Not specified	UNKNOWN	Spanish Registry of RYR1 and CACNA1S Polymorphisms
NCT04474860	Not specified	UNKNOWN	Gene Mutation Spectrum of Malignant Hyperthermia in China
NCT04610619	Not specified	UNKNOWN	Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants
NCT05036148	Not specified	COMPLETED	Malignant Hyperthermia in Czech Republic: Description of the Biggest Slavonic Group of Patients Investigated for Risk of Malignant Hyperthermia