Malignant Hyperthermia Susceptibility malady

MalaCards: Malignant Hyperthermia Susceptibility, also known as malignant hyperpyrexia due to anesthesia, is related to malignant hyperthermia and myopathy. An important gene associated with Malignant Hyperthermia Susceptibility is RYR1 (ryanodine receptor 1 (skeletal)), and among its related pathways are DREAM Repression and Dynorphin Expression and Fc-Gamma-RIIB Signaling in B-Cells. The drugs dantrolene sodium and dantrolene and the compounds fluspirilene and succinylcholine have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle and b cells, and related mouse phenotypes are cardiovascular system and muscle.

GeneReviews summary for mhs

malignant hyperthermia susceptibility 15 16 malignant hyperpyrexia due to anesthesia 43

hyperpyrexia, malignant 16 malignant hyperpyrexia 15

Disease types for malignant hyperthermia susceptibility family:

malignant hyperthermia susceptibility type 1	malignant hyperthermia susceptibility type 2
malignant hyperthermia susceptibility type 3	malignant hyperthermia susceptibility type 4
malignant hyperthermia susceptibility type 5	malignant hyperthermia susceptibility type 6

Diseases related to malignant hyperthermia susceptibility by text searches and GeneDecks gene sharing:

(show all 47)

id	Related Disease	Score	Top Affiliating Genes
1	malignant hyperthermia	27.8	CACNA1S, PIK3C2A, ASPH, MHS2, MHS3, MHS4
2	myopathy	26.2	CACNA1S, CPT2, RYR2, RYR1, SRL, IL6
3	hypokalemic periodic paralysis	13.1	CACNA1S, RYR1
4	vibrio vulnificus infection	12.8	IL6, PIK3C2A
5	rhabdomyolysis, cerivastatin-induced	12.8	PIK3C2A, RYR1, CPT2
6	catecholaminergic polymorphic ventricular tachycardia	12.7	RYR1, RYR2
7	nephropathia epidemica	12.7	IL6, PIK3C2A
8	central core myopathy	12.6	CACNA1S, RYR2, RYR1
9	neuroleptic malignant syndrome	12.6	RYR1, HTR2A, PIK3C2A
10	borderline personality disorder	12.3	IL6, HTR2A
11	convulsions	12.3	PIK3C2A, IL6, CPT2
12	respiratory failure	12.2	CPT2, RYR1, IL6, PIK3C2A
13	coronary stenosis	12.2	PIK3C2A, IL6, HTR2A
14	hyperuricemia	12.1	PIK3C2A, IL6, HTR2A, CACNA1S
15	myasthenia gravis	12.0	CACNA1S, RYR2, RYR1, IL6
16	congenital myasthenic syndrome	12.0	IL6, RYR1, RYR2, CACNA1S
17	congestive heart failure	12.0	PIK3C2A, RYR2, CPT2
18	sudden cardiac death multi-gene panels	12.0	HTR2A, CALR, RYR2
19	secondary hyperparathyroidism of renal origin	12.0	CACNA1S, RYR2, RYR1, IL6
20	arrhythmogenic right ventricular dysplasia/cardiomyopathy multi-gene panels	11.9	RYR2, RYR1, ASPH, PIK3C2A
21	hyperparathyroidism	11.9	CACNA1S, RYR2, RYR1, IL6
22	oculomotor apraxia cogan type	11.7	CPT2, HTR2A, IL6, PIK3C2A
23	congenital heart defect	11.7	RYR2, RYR1, HTR2A, PIK3C2A
24	atrial fibrillation	11.6	RYR2, CACNB1, IL6, PIK3C2A
25	sudden infant death syndrome	11.6	IL6, HTR2A, RYR2
26	neuropathy	11.0	RYR1, CACNA2D1, HTR2A, IL6, PIK3C2A
27	hypoxia	10.5	CPT2, RYR2, RYR1, ANXA6, IL6, ASPH
28	diabetes mellitus	10.3	CPT2, CALR, CACNA2D1, HTR2A, IL6, PIK3C2A
29	neuroblastoma	10.1	RYR2, RYR1, CALR, CACNA2D1, CACNB1, HTR2A
30	hypertrophic cardiomyopathy	9.8	CACNA1S, RYR2, CALR, CACNA2D1, CACNG1, CACNB1
31	dmd-associated dilated cardiomyopathy	9.5	CACNA1S, CPT2, RYR2, RYR1, CALR, CACNA2D1
32	noonan syndrome	8.9	CALR, RYR1, RYR2, CPT2, CACNA1S, CACNA2D1
33	neuronitis	8.8	CACNA1S, RYR2, RYR1, CALR, CACNA2D1, CACNG1
34	malignant hyperthermia susceptibility type 1	8.7
35	malignant hyperthermia susceptibility type 2	8.7
36	malignant hyperthermia susceptibility type 3	8.7
37	malignant hyperthermia susceptibility type 4	8.7
38	malignant hyperthermia susceptibility type 5	8.7
39	malignant hyperthermia susceptibility type 6	8.7
40	malignant hyperthermia arthrogryposis torticollis	8.2
41	mhs3-related malignant hyperthermia susceptibility	7.8
42	mhs4-related malignant hyperthermia susceptibility	7.8
43	mhs6-related malignant hyperthermia susceptibility	7.8
44	ryr1-related malignant hyperthermia susceptibility	7.8
45	cacna1s-related malignant hyperthermia susceptibility	7.8
46	mhs2-related malignant hyperthermia susceptibility	7.8
47	king denborough syndrome	6.4

Approved drugs:

Drug clinical trials:

Inferred drug relations via UMLS/NDF-RT:

^43 28 dantrolene, dantrolene sodium

MalaCards organs/tissues related to malignant hyperthermia susceptibility:

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MGI Mouse Phenotypes related to malignant hyperthermia susceptibility:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cardiovascular system phenotype	MP:0005385	6.9	IL6, ANXA6, CACNA2D1, CALR, SRL, RYR1
2	muscle phenotype	MP:0005369	5.3	CACNA1S, HTR2A, CACNB1, CACNG1, CACNA2D1, CALR

Articles related to malignant hyperthermia susceptibility:

(show all 25)

id	Title	Authors	Year	Affiliating Genes
1	Novel variants near the central domain of RYR1 in two malignant hyperthermia-susceptible families from Taiwan. (19762757)	Chen P.L.... Day Y.J.	2009	RYR1
2	Identification of malignant hyperthermia-susceptible ryanodine receptor type 1 gene (RYR1) mutations in a child who died in a car af ter exposure to a high environmental temperature. (19223216)	Nishio H.... Suzuki K.	2009	RYR1
3	Epigenetic allele silencing and variable penetrance o f malignant hyperthermia susceptibility. (19454545)	Robinson R.L.... Shaw M.A.	2009	RYR1
4	No carnitine palmitoyltransferase deficiency in skeletal muscle in 18 malignant hyperthermia susceptible individuals. (18430572)	Wieser T.... Kress H.G.	2008	CPT2
5	Malignant hyperthermia susceptibility diagnosed with a family-specific ryanodine receptor gene type 1 mutation. (18306019)	Tanabe T.... Nishino I.	2008	RYR1
6	Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility. (16163667)	Monnier N.... Lunardi J.	2005	CACNA1S
7	Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population. (15731587)	Sambuughin N.... Goldfarb L.G.	2005	RYR1
8	Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease. (15299003)	Ducreux S.... Treves S.	2004	IL6, RYR1
9	Multiminicore myopathy, central core disease, malignant hyperthermia susceptibility, and RYR1 mutations: one disease with many faces? (14732615)	Mathews K.D.... Moore S.A.	2004	RYR1
10	Increased sensitivity of the ryanodine receptor to halothane-induced oligomerization in malignant hyperthermia-susceptible human skeletal muscle. (12959958)	Glover L.... Ohlendieck K.	2004	CALR, RYR1, ANXA6
11	Phenotyping malignant hyperthermia susceptibility by measuring halothane-induced changes in myoplasmic calcium concentration in cult ured human skeletal muscle cells. (12393358)	Girard T.... Urwyler A.	2002	RYR1
12	Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility. (12411788)	Monnier N.... Lunardi J.	2002	CACNA1S
13	Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype. (11389482)	Sambuughin N.... Nelson T.E.	2001	RYR1
14	B-lymphocytes from malignant hyperthermia-susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators. (11673462)	Girard T.... Treves S.	2001	RYR1, RYR2
15	5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients. (10551274)	Wappler F.... Schulte am Esch J.	1999	HTR2A
16	Intracellular calcium homeostasis in human primary mu scle cells from malignant hyperthermia-susceptible and normal individuals. Effe ct Of overexpression of recombinant wild-type and Arg163Cys mutated ryanodine r eceptors. (9502764)	Censier K.... Treves S.	1998	RYR1
17	Muscular enzyme level disorders and a malignant hyperthermia susceptability test: postoperative study of a patient with elevated CPK (9658790)	Perugini M.... Rocchi S.	1998	PIK3C2A
18	Malignant-hyperthermia susceptibility is associated with a mutation of the alpha-1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. (9199552)	Monnier N.... Lunardi J.	1997	CACNA1S
19	Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle. (9030597)	Richter M.... Herrmann-Frank A.	1997	RYR1
20	Mapping of a further malignant hyperthermia susceptibility locus to chromosome 3q13.1. (7887423)	Sudbrak R.... Kozak-Ribbens G.	1995	MHS4
21	Ryanodine receptor gene point mutation and malignant hyperthermia susceptibility. (7751854)	Moroni I.... Scarlato G.	1995	RYR1
22	Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. (7951247)	Iles D.E.... Ellis F.R.	1994	CACNA2D1
23	Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha 1, beta 1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect. (8395939)	Sudbrak R.... Deufel T.	1993	CACNA1S
24	Genetic mapping of the beta 1- and gamma-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility. (8395940)	Iles D.E.... Wieringa B.	1993	RYR1, CACNB1, CACNG1
25	Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q. (1427885)	Levitt R.C.... Meyers D.A.	1992	MHS2

Genes related to malignant hyperthermia susceptibility according to GeneCards:

(show all 18)

id	Symbol	Description	Score	GeneCards Section Context
1	RYR1	ryanodine receptor 1 (skeletal)	11.1	Summaries, Publications
2	CACNA1S	calcium channel, voltage-dependent, L type, alpha 1S subunit	11.1	Publications, Summaries
3	MHS3	Malignant hyperthermia susceptibility 3	11.1	Aliases & Descriptions
4	MHS4	malignant hyperthermia susceptibility 4	11.1	Aliases & Descriptions, Publications
5	MHS6	malignant hyperthermia susceptibility 6	11.1	Aliases & Descriptions
6	MHS2	malignant hyperthermia susceptibility 2	11.1	Publications, Aliases & Descriptions
7	CACNG1	calcium channel, voltage-dependent, gamma subunit 1	11.0	Publications
8	CACNB1	calcium channel, voltage-dependent, beta 1 subunit	11.0	Publications
9	SRL	sarcalumenin	11.0	Publications
10	ASPH	aspartate beta-hydroxylase	11.0	Publications
11	CALR	calreticulin	11.0	Publications
12	CPT2	carnitine palmitoyltransferase 2	11.0	Publications
13	ANXA6	annexin A6	11.0	Publications
14	PIK3C2A	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha	11.0	Publications
15	HTR2A	5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled	11.0	Publications
16	CACNA2D1	calcium channel, voltage-dependent, alpha 2/delta subunit 1	11.0	Publications
17	RYR2	ryanodine receptor 2 (cardiac)	11.0	Publications
18	IL6	interleukin 6 (interferon, beta 2)	11.0	Publications

Pathways related to malignant hyperthermia susceptibility according to GeneDecks:

(show all 47)

id	Pathway	Score	Top Affiliating Genes
1	DREAM Repression and Dynorphin Expression36	9.5	CACNA2D1, CACNG1, CACNB1, CACNA1S
2	Fc-Gamma-RIIB Signaling in B-Cells36	9.5	CACNA2D1, CACNB1, CACNA1S, CACNG1
3	Fc-GammaR Pathway36	9.5	CACNA1S, CACNA2D1, CACNG1, CACNB1
4	CCR5 Pathway in Macrophages36	9.5	CACNB1, CACNG1, CACNA1S, CACNA2D1
5	BMP Pathway36	9.5	CACNB1, CACNG1, CACNA1S, CACNA2D1
6	Caspase Cascade36	9.5	CACNA2D1, CACNB1, CACNG1, CACNA1S
7	Transcription CREB pathway10	9.5	CACNB1, CACNA2D1, CACNA1S, CACNG1
8	Fc-EpsilonRI Pathway36	9.4	CACNG1, CACNB1, CACNA2D1, CACNA1S
9	PDGF Pathway36	9.4	CACNG1, CACNA2D1, CACNB1, CACNA1S
10	Transcription_CREB pathway41	9.4	CACNA1S, CACNA2D1, CACNG1, CACNB1
11	Celecoxib Pathway, Pharmacodynamics34	9.4	CACNA2D1, CACNA1S, CACNB1
12	Calpain Protease Regulates Cellular Mechanics36	9.4	CACNA1S, CACNG1, CACNB1, CACNA2D1
13	GHRH Signaling36	9.4	CACNG1, CACNA1S, CACNB1, CACNA2D1
14	G-Beta Gamma Signaling36	9.4	CACNB1, CACNA2D1, CACNA1S, CACNG1
15	PKC-Theta Pathway36	9.4	CACNA2D1, CACNA1S, CACNB1, CACNG1
16	Sweet Taste Signaling36	9.4	CACNA1S, CACNA2D1, CACNG1, CACNB1
17	ITK and TCR Signaling36	9.4	CACNA1S, CACNG1, CACNB1, CACNA2D1
18	IGF1R Signaling36	9.3	CACNB1, CACNA1S, CACNA2D1, CACNG1
19	Melatonin Signaling36	9.3	CACNA1S, CACNA2D1, CACNB1, CACNG1
20	TCR Signaling36	9.3	CACNG1, CACNA1S, CACNA2D1, CACNB1
21	CRHR Pathway36	9.3	CACNB1, CACNG1, CACNA2D1, CACNA1S
22	Chemokine Signaling36	9.3	CACNA2D1, CACNA1S, CACNB1, CACNG1
23	Beta-Adrenergic Signaling36	9.2	RYR1, RYR2, CACNA1S
24	Cellular Effects of Sildenafil36	9.2	CACNA1S, CACNG1, CACNB1, CACNA2D1
25	Androgen Signaling36	9.2	CACNB1, CACNA2D1, CACNG1, CALR, CACNA1S
26	GnRH Signaling36	9.1	CACNG1, CACNA2D1, CACNA1S, CACNB1
27	MAPK signaling pathway20	9.0	CACNA1S, CACNG1, CACNB1, CACNA2D1
28	NFAT Signaling and Lymphocyte Interactions36	9.0	CACNG1, IL6, CACNA1S, CACNB1, CACNA2D1
29	all-trans-Retinoic Acid Signaling in Brain36	9.0	CACNA1S, CACNA2D1, IL6, CACNB1, CACNG1
30	NFAT and Cardiac Hypertrophy36	9.0	CACNG1, CACNA2D1, CACNA1S, CACNB1, IL6
31	Signaling Involved in Cardiac Hypertrophy36	8.9	IL6, CACNB1, CACNG1, CACNA2D1, CACNA1S
32	IP3 Pathway36	8.9	CACNA2D1, IL6, CACNB1, CACNG1, CACNA1S
33	Rap1 Pathway36	8.9	CACNB1, CACNA2D1, CACNA1S, CACNG1, IL6
34	CREB Pathway36	8.9	CACNA1S, IL6, CACNB1, CACNG1, CACNA2D1
35	Calcium signaling pathway20	8.9	CACNA1S, RYR2, RYR1, HTR2A
36	Arrhythmogenic right ventricular cardiomyopathy (ARVC)20	8.7	CACNA1S, CACNA2D1, CACNB1, CACNG1, RYR2
37	Cardiac muscle contraction20	8.7	RYR2, CACNA1S, CACNG1, CACNB1, CACNA2D1
38	Dilated cardiomyopathy20	8.7	CACNB1, CACNG1, CACNA1S, RYR2, CACNA2D1
39	nNOS Signaling in Skeletal Muscle36	8.5	RYR2, RYR1, CACNA2D1, CACNG1, CACNB1, CACNA1S
40	Netrin Signaling36	8.5	CACNA2D1, CACNB1, CACNA1S, RYR2, RYR1, CACNG1
41	PKA Signaling36	8.5	CACNA2D1, CACNG1, CACNB1, RYR1, RYR2, CACNA1S
42	ERK Signaling36	8.3	IL6, CACNB1, CACNG1, CACNA2D1, CACNA1S
43	Hypertrophic cardiomyopathy (HCM)20	8.2	CACNB1, CACNG1, CACNA2D1, IL6, RYR2, CACNA1S
44	Presenilin-Mediated Signaling36	8.2	CACNB1, CACNG1, CACNA2D1, CALR, RYR1, RYR2
45	Activation of cAMP-Dependent PKA36	8.0	CACNG1, RYR2, RYR1, CACNA2D1, CACNA1S, CACNB1
46	cAMP Pathway36	8.0	CACNA2D1, CACNB1, CACNA1S, RYR2, CACNG1, IL6
47	Intracellular Calcium Signaling36	7.5	HTR2A, IL6, RYR1, CACNA2D1, CACNG1, RYR2

Compounds related to malignant hyperthermia susceptibility according to GeneDecks:

(show all 23)

id	Compound	Score	Top Affiliating Genes
1	fluspirilene32 9 9	12.0	HTR2A, CACNG1
2	succinylcholine32 9 9	11.9	PIK3C2A, RYR1
3	h2o32	9.8	RYR1, PIK3C2A
4	nisoldipine32 9 9	11.8	CACNA1S, CACNA2D1
5	ibutilide32 9 9	11.8	CACNA2D1, CACNG1
6	4-chloro-m-cresol32	9.7	RYR1, RYR2
7	halothane32 9 9	11.7	CALR, PIK3C2A, RYR1
8	Magnesium Sulfate9 9	10.7	CACNA2D1, CACNG1, CACNA1S
9	isradipine32 9 42 9	12.7	CACNA1S, CACNA2D1
10	nitrendipine32 9 9	11.7	CACNA1S, CACNA2D1, CACNG1
11	nilvadipine32 9 9	11.6	CACNA1S, CACNA2D1
12	cyclic adp-ribose32	9.6	RYR1, RYR2
13	amlodipine32 9 18 9	12.4	CACNA2D1, CACNG1, CACNB1, CACNA1S
14	dantrolene32 9 9	11.3	RYR1, RYR2, PIK3C2A
15	verapamil32 34 9 18 9	13.2	RYR2, CACNG1, CACNA1S, CACNB1
16	ruthenium32	9.2	RYR1, RYR2
17	dihydropyridine32	9.0	CACNA1S, RYR1, ASPH, ANXA6, CALR, SRL
18	norepinephrine32 9 18 9	11.7	PIK3C2A, IL6, RYR1, HTR2A
19	ryanodine32	8.2	RYR2, CACNA1S, RYR1, SRL, CALR, ASPH
20	glutamate32	8.1	PIK3C2A, CPT2, RYR2, RYR1, CALR, ANXA6
21	atp32	7.9	SRL, RYR2, ANXA6, PIK3C2A, RYR1, CALR
22	lipid32	7.6	IL6, PIK3C2A, RYR1, CALR, CPT2, RYR2
23	calcium32 9 18 9	9.1	CACNA2D1, CALR, RYR1, RYR2, CACNA1S, CACNG1

Cellular components related to malignant hyperthermia susceptibility according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	I band	GO:031674	10.1	RYR1, CACNA1S
2	T-tubule	GO:030315	9.7	CACNA1S, RYR1, CACNB1
3	sarcoplasmic reticulum lumen	GO:033018	9.5	CALR, SRL
4	voltage-gated calcium channel complex	GO:005891	9.2	CACNB1, CACNA1S, CACNA2D1, CACNG1
5	junctional sarcoplasmic reticulum membrane	GO:014701	9.1	RYR1, RYR2, ASPH
6	sarcoplasmic reticulum	GO:016529	9.0	CACNA1S, RYR2, RYR1, CACNB1

Biological processes related to malignant hyperthermia susceptibility according to GeneDecks:

(show all 7)

id	Name	GO ID	Score	Top Affiliating Genes
1	muscle contraction	GO:006936	9.6	CACNA1S, RYR1, CACNG1, ASPH
2	cellular response to caffeine	GO:071313	9.5	RYR1, RYR2
3	cytosolic calcium ion homeostasis	GO:051480	9.5	RYR1, RYR2
4	release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	GO:014808	9.4	RYR2, RYR1
5	response to caffeine	GO:031000	9.2	RYR2, RYR1
6	release of sequestered calcium ion into cytosol	GO:051209	9.0	RYR2, RYR1, HTR2A
7	calcium ion transport	GO:006816	8.4	ANXA6, CACNA2D1, RYR1, RYR2, CACNA1S

Molecular functions related to malignant hyperthermia susceptibility according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	high voltage-gated calcium channel activity	GO:008331	9.7	CACNA1S, CACNB1
2	ryanodine-sensitive calcium-release channel activity	GO:005219	9.5	RYR1, RYR2
3	calcium-release channel activity	GO:015278	9.4	RYR1, RYR2
4	voltage-gated calcium channel activity	GO:005245	9.0	RYR1, CACNA1S, CACNB1, CACNG1, CACNA2D1
5	calcium ion binding	GO:005509	8.4	RYR1, RYR2, CALR, ASPH, ANXA6