HYPP
MCID: HYP052
MIFTS: 62

Hyperkalemic Periodic Paralysis (HYPP)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hyperkalemic Periodic Paralysis

MalaCards integrated aliases for Hyperkalemic Periodic Paralysis:

Name: Hyperkalemic Periodic Paralysis 57 12 73 25 20 43 58 36 29 54 6 15 70
Familial Hyperkalemic Periodic Paralysis 12 43 58 29 6
Gamstorp Disease 57 20 43 58 72
Hypp 57 20 58 72
Adynamia Episodica Hereditaria with or Without Myotonia 57 20 72
Gamstorp Episodic Adynamy 20 43 58
Hyperpp 25 43 58
Hyperkalemic Periodic Paralysis, Type 2 57 13
Primary Hyperkalemic Periodic Paralysis 43 58
Adynamia Episodica Hereditaria 43 58
Hyperkpp 43 58
Paralysis, Periodic, Hyperkalemic 39
Paralysis, Hyperkalemic Periodic 44
Periodic Paralysis Hyperkalemic 72
Periodic Paralysis Normokalemic 72
Sodium Channel Muscle Disease 20
Potassium Aggravated Myotonia 70
Periodic Paralysis Eukalemic 72
Familial Hyperpp 58
Hyperkalemic Pp 58
Primary Hyperpp 58
Nkpp 72

Characteristics:

Orphanet epidemiological data:

58
hyperkalemic periodic paralysis
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy or early childhood
allelic disorder to potassium-aggravated myotonia
allelic disorder to hypokalemic periodic paralysis (hokpp, )
variable phenotype (myotonia may or may not be present)
acetazolamide is often effective
allelic disorder to paramyotonia congenita


HPO:

31
hyperkalemic periodic paralysis:
Onset and clinical course death in infancy death in early adulthood infantile onset
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Usually, the penetrance is high (>90%). a few individuals with rare heterozygous pathogenic variants do not present with clinically detectable symptoms but have signs of myotonia detectable by emg only [mcclatchey et al 1992, wagner et al 1997].

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:14451
OMIM® 57 170500
KEGG 36 H00745
MeSH 44 D020513
NCIt 50 C123429
SNOMED-CT 67 304737009
ICD10 32 G72.3
MESH via Orphanet 45 C535409 D020513
ICD10 via Orphanet 33 G72.3
UMLS via Orphanet 71 C0238357 C2930895
Orphanet 58 ORPHA682
UMLS 70 C0238357 C2931826

Summaries for Hyperkalemic Periodic Paralysis

GARD : 20 Hyperkalemic periodic paralysis is a genetic disease that causes episodes of extreme muscle weakness and an increase of the potassium levels in the blood. Muscle weakness during an attack usually affects the arms and legs and muscles of the eyes, throat, and trunk. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes usually begin before age 20, usually between infancy and age 10. Normally an episode lasts for 15 minutes to an hour, but in some people the episodes may last a few days to a week. Episodes tend to increase in frequency until about age 50, after which they may occur less frequently. Factors that can trigger attacks include rest after strenuous exercise, potassium-rich foods, stress, fatigue, and exposure to cold. Depolarizing anesthetics should also be avoided. Muscle strength usually returns to normal between episodes, although many people continue to experience mild stiffness, particularly in muscles of the face and hands. Studies suggest more than 80% of people with hyperkalemic periodic paralysis over age 40 have permanent muscle weakness, most often affecting the leg muscles. About one third may develop a chronic progressive myopathy. Hyperkalemic periodic paralysis is caused by mutations in the SCN4A gene and is inherited in an autosomal dominant manner. Diagnosis is based on clinical symptoms including the increase of blood potassium level during an episode, but normal levels of blood potassium level in between episodes. Genetic testing can confirm the diagnosis. Treatment is focused on avoiding triggers and decreasing the severity of an episode. At the first sign of muscle weakness, episodes in many people may be prevented or stopped by mild exercise and/or eating carbohydrates, inhalation of salbutamol, or intravenous calcium gluconate.

MalaCards based summary : Hyperkalemic Periodic Paralysis, also known as familial hyperkalemic periodic paralysis, is related to periodic paralyses and periodic paralysis, and has symptoms including myalgia, stridor and muscular stiffness. An important gene associated with Hyperkalemic Periodic Paralysis is SCN4A (Sodium Voltage-Gated Channel Alpha Subunit 4), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and Developmental Biology. The drugs Dichlorphenamide and Hops have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, eye and heart, and related phenotypes are elevated serum creatine kinase and emg abnormality

MedlinePlus Genetics : 43 Hyperkalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness or paralysis, usually beginning in infancy or early childhood. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes tend to increase in frequency until mid-adulthood, after which they occur less frequently in many people with the condition. Factors that can trigger attacks include rest after exercise, potassium-rich foods such as bananas and potatoes, stress, fatigue, alcohol, pregnancy, exposure to hot or cold temperatures, certain medications, and periods without food (fasting). Muscle strength usually returns to normal between attacks, although many affected people continue to experience mild stiffness (myotonia), particularly in muscles of the face and hands.Most people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. Hyperkalemia results when the weak or paralyzed muscles release potassium ions into the bloodstream. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up.

OMIM® : 57 The 2 dominantly inherited, clinically similar types of episodic flaccid generalized weakness, HOKPP and HYPP, are distinguished by the changes in serum potassium levels during paralytic attacks. An important clinical difference between the 2 entities is represented by the triggers of attacks of weakness, e.g., HYPP can be provoked by oral potassium administration, whereas this is a remedy for HOKPP. Concurrence of myotonia is found in HYPP but usually not in HOKPP patients (Jurkat-Rott et al., 2000). Jurkatt-Rott and Lehmann-Horn (2007) provided a review of the clinical features, pathogenesis, and therapeutic options for HYPP. (170500) (Updated 20-May-2021)

KEGG : 36 The periodic paralyses are a group of autosomal-dominant disorders of skeletal muscle sodium, potassium, and calcium channel genes. They are characterized by episodes of muscle weakness associated with variations in serum potassium concentration. Hyperkalemic periodic paralysis (HyperPP) is caused by gain-of-function mutations in the alpha-subunit of the skeletal muscle voltage-gated sodium channel, Nav1.4. However, 20% of cases remain genetically undefined, suggesting genetic heterogeneity. HyperPP is characterized by attacks of flaccid limb paralysis or, rarely, weakness of the eye and throat muscles. Triggers for these attacks include ingestion of potassium-rich food, rest after strenuous exercise, and cold exposure.

UniProtKB/Swiss-Prot : 72 Periodic paralysis hyperkalemic: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients.
Periodic paralysis normokalemic: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness.

Wikipedia : 73 Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that... more...

GeneReviews: NBK1496

Related Diseases for Hyperkalemic Periodic Paralysis

Diseases related to Hyperkalemic Periodic Paralysis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 133)
# Related Disease Score Top Affiliating Genes
1 periodic paralyses 32.1 SCN4A KCNJ2 KCNE3 GH-LCR CACNA1S
2 periodic paralysis 31.7 SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
3 myotonia 31.4 SCN4A GH-LCR CNBP CLCN1
4 graves disease 1 30.7 SCN4A KCNJ18 CACNA1S
5 hypokalemia 30.7 SCN4A KCNJ18 CACNA1S
6 malignant hyperthermia 30.4 SCN5A SCN4A RYR1 CACNA1S
7 myopathy 30.2 SCN4A RYR1 GH-LCR GBE1 CNBP CLCN1
8 neuromuscular disease 30.0 SCN5A SCN4A RYR1 CNBP CLCN1 CACNA1S
9 myotonia congenita 29.6 SCN4A KCNJ2 GLRB GH-LCR CNBP CLCN1
10 paramyotonia congenita of von eulenburg 29.5 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
11 andersen cardiodysrhythmic periodic paralysis 29.5 SCN5A SCN4A KCNJ2 KCNJ18 KCNE3 GBE1
12 hypokalemic periodic paralysis, type 1 29.2 SCN5A SCN4A SCN2A RYR1 NAV1 KCNJ2
13 familial periodic paralysis 28.8 SCN5A SCN4A SCN2A RYR1 NAV1 KCNJ2
14 myotonia, potassium-aggravated 11.4
15 familial periodic paralyses 11.3
16 tremor 10.4
17 normokalemic periodic paralysis 10.4 SCN4A GH-LCR
18 hypokalemic periodic paralysis, type 2 10.4 SCN4A GH-LCR
19 neuropathy, hereditary sensory and autonomic, type vii 10.4 SCN4A CACNA1S
20 central nervous system origin vertigo 10.4 SCN2A CLCN1
21 cardiac arrhythmia 10.3
22 febrile seizures, familial, 5 10.3 SCN2A SCN1A
23 first-degree atrioventricular block 10.3 SCN5A KCNJ2
24 reflex epilepsy 10.3 SCN2A SCN1A
25 brugada syndrome 6 10.3 SCN5A KCNE3
26 febrile seizures, familial, 2 10.3 SCN2A SCN1A
27 quadriplegia 10.3
28 myotonic dystrophy 10.3
29 long qt syndrome 14 10.3 SCN5A KCNJ2
30 long qt syndrome 10 10.3 SCN5A KCNJ2
31 early onset absence epilepsy 10.3 SCN2A SCN1A
32 thyrotoxic periodic paralysis 1 10.3 KCNJ18 CACNA1S
33 long qt syndrome 13 10.3 SCN5A KCNJ2
34 myotonic dystrophy 2 10.3 SCN4A CNBP CLCN1
35 timothy syndrome 10.3 SCN5A KCNJ2 CACNA1S
36 myasthenic syndrome, congenital, 16 10.2 SCN4A GH-LCR
37 headache 10.2 SCN1A CLCN1 CACNA1S
38 long qt syndrome 5 10.2 SCN5A KCNJ2 KCNE3
39 long qt syndrome 6 10.2 SCN5A KCNJ2 KCNE3
40 familial hemiplegic migraine 10.2 SCN5A SCN1A CACNA1S
41 metal metabolism disorder 10.2 SCN4A KCNJ18 CACNA1S
42 short qt syndrome 10.2 SCN5A KCNJ2 KCNE3
43 jervell and lange-nielsen syndrome 1 10.2 SCN5A KCNJ2 KCNE3
44 landau-kleffner syndrome 10.2 SCN2A SCN1A
45 atrophic muscular disease 10.2 RYR1 CLCN1
46 generalized epilepsy with febrile seizures plus, type 1 10.2 SCN1A PTPRZ1
47 episodic pain syndrome, familial, 3 10.2 SCN9A NAV1
48 long qt syndrome 2 10.2 SCN5A KCNJ2 KCNE3
49 myopathy, congenital, bailey-bloch 10.2 RYR1 CACNA1S
50 brugada syndrome 4 10.2 SCN5A KCNJ2

Graphical network of the top 20 diseases related to Hyperkalemic Periodic Paralysis:



Diseases related to Hyperkalemic Periodic Paralysis

Symptoms & Phenotypes for Hyperkalemic Periodic Paralysis

Human phenotypes related to Hyperkalemic Periodic Paralysis:

58 31 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 elevated serum creatine kinase 58 31 hallmark (90%) Very frequent (99-80%) HP:0003236
2 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
3 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
4 episodic flaccid weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003752
5 periodic hyperkalemic paralysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0007215
6 cerebral palsy 58 31 hallmark (90%) Very frequent (99-80%) HP:0100021
7 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
8 myotonia 58 31 frequent (33%) Frequent (79-30%) HP:0002486
9 myalgia 58 31 frequent (33%) Frequent (79-30%) HP:0003326
10 fasciculations 58 31 frequent (33%) Frequent (79-30%) HP:0002380
11 hyperkalemia 58 31 frequent (33%) Frequent (79-30%) HP:0002153
12 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
13 bowel incontinence 58 31 occasional (7.5%) Occasional (29-5%) HP:0002607
14 hypertonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001276
15 flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0001371
16 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
17 hypokalemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002900
18 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
19 skeletal muscle atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003202
20 congestive heart failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0001635
21 malignant hyperthermia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002047
22 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
23 hyponatremia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002902
24 paresthesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003401
25 chest pain 58 31 occasional (7.5%) Occasional (29-5%) HP:0100749
26 ophthalmoparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000597
27 skeletal muscle hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003712
28 death in infancy 58 Occasional (29-5%)
29 death in early adulthood 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Muscle Soft Tissue:
flaccid weakness or paralysis, episodic attacks
muscle weakness is predominantly of extremities and tongue
attacks precipitated by rest after exercise
attacks precipitated by cold temperature
attacks precipitated by potassium
more
Laboratory Abnormalities:
hyperkalemia during attacks

Clinical features from OMIM®:

170500 (Updated 20-May-2021)

UMLS symptoms related to Hyperkalemic Periodic Paralysis:


myalgia; stridor; muscular stiffness

MGI Mouse Phenotypes related to Hyperkalemic Periodic Paralysis:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.2 CACNA1S CLCN1 CNBP GBE1 GLRB KCNJ2
2 mortality/aging MP:0010768 10.1 CACNA1S CLCN1 CNBP GBE1 GLRB KCNJ2
3 muscle MP:0005369 9.81 CACNA1S CLCN1 GBE1 GLRB KCNJ2 RYR1
4 nervous system MP:0003631 9.73 CACNA1S CLCN1 CNBP GBE1 GLRB KCNE3
5 respiratory system MP:0005388 9.32 CACNA1S GBE1 KCNE3 KCNJ2 RYR1 SCN1A

Drugs & Therapeutics for Hyperkalemic Periodic Paralysis

Drugs for Hyperkalemic Periodic Paralysis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dichlorphenamide Approved, Investigational Phase 3 120-97-8 3038
2 Hops Approved Phase 3
3
Lamotrigine Approved, Investigational Phase 3 84057-84-1 3878
4 Carbonic Anhydrase Inhibitors Phase 3
5 Psychotropic Drugs Phase 3
6 Sodium Channel Blockers Phase 3
7 Hormones Phase 3
8 Anticonvulsants Phase 3
9 Diuretics, Potassium Sparing Phase 3
10 calcium channel blockers Phase 3
11 Antipsychotic Agents Phase 3
12 Calcium, Dietary Phase 3
13
Calcium Nutraceutical Phase 3 7440-70-2 271

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Dichlorphenamide vs. Placebo for Periodic Paralysis Completed NCT00494507 Phase 3 Dichlorphenamide (double-blind);Placebo (double-blind);Dichlorphenamide (open-label)
2 Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders Completed NCT00004802 Phase 3 dichlorphenamide
3 Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study Completed NCT01939561 Phase 3 Lamotrigine;Placebo

Search NIH Clinical Center for Hyperkalemic Periodic Paralysis

Cochrane evidence based reviews: paralysis, hyperkalemic periodic

Genetic Tests for Hyperkalemic Periodic Paralysis

Genetic tests related to Hyperkalemic Periodic Paralysis:

# Genetic test Affiliating Genes
1 Familial Hyperkalemic Periodic Paralysis 29 SCN4A
2 Hyperkalemic Periodic Paralysis 29

Anatomical Context for Hyperkalemic Periodic Paralysis

MalaCards organs/tissues related to Hyperkalemic Periodic Paralysis:

40
Skeletal Muscle, Eye, Heart, Tongue, Temporal Lobe, Bone, Kidney

Publications for Hyperkalemic Periodic Paralysis

Articles related to Hyperkalemic Periodic Paralysis:

(show top 50) (show all 418)
# Title Authors PMID Year
1
Identification of a mutation in the gene causing hyperkalemic periodic paralysis. 6 57 25 54 61
1659948 1991
2
New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. 57 25 6
15596759 2004
3
Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A. 57 6 25
12933953 2003
4
Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. 6 57 25
10944223 2000
5
Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. 25 57 6
1338909 1992
6
Correlating phenotype and genotype in the periodic paralyses. 57 6 61
15534250 2004
7
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. 25 54 6 61
10930446 2000
8
Prevalence study of genetically defined skeletal muscle channelopathies in England. 6 61 25
23516313 2013
9
A novel N440K sodium channel mutation causes myotonia with exercise-induced weakness--exclusion of CLCN1 exon deletion/duplication by MLPA. 25 6 61
22106717 2011
10
Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis. 6 25 61
17395131 2007
11
Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family. 57 6
15642860 2005
12
Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. 57 6
14504341 2003
13
Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5. 6 25 61
11971097 2002
14
Hyperkalemic periodic paralysis and paramyotonia congenita--a novel sodium channel mutation. 61 6 25
11757950 2001
15
A novel sodium channel mutation causing a hyperkalemic paralytic and paramyotonic syndrome with variable clinical expressivity. 61 25 6
9339683 1997
16
Paramyotonia congenita and hyperkalemic periodic paralysis associated with a Met 1592 Val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype. 6 61 25
9131651 1997
17
Paramyotonia congenita: genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene. 6 25 61
8902732 1996
18
Myotonia fluctuans. A third type of muscle sodium channel disease. 61 6 25
7980103 1994
19
A novel SCN4A mutation causing myotonia aggravated by cold and potassium. 61 25 6
8242056 1993
20
A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis. 6 25 61
1659668 1991
21
Progressive myopathy in hyperkalemic periodic paralysis. 61 57 25
2396930 1990
22
Mutations of SCN4A gene cause different diseases: 2 case reports and literature review. 25 6
25839108 2015
23
The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis. 6 25
18162704 2007
24
Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK. 6 25
11591859 2001
25
Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica. 25 6
11309455 2001
26
A novel sodium channel mutation in a family with hypokalemic periodic paralysis. 25 6
10599760 1999
27
Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans. 6 25
10381583 1999
28
Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation. 25 6
10366610 1999
29
Familial cramp due to potassium-aggravated myotonia. 6 25
9771789 1998
30
Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree. 54 61 57
9508059 1998
31
Paramyotonia congenita: the R1448P Na+ channel mutation in adult human skeletal muscle. 6 25
8619545 1996
32
Mutations in the muscle sodium channel gene (SCN4A) in 13 French families with hyperkalemic periodic paralysis and paramyotonia congenita: phenotype to genotype correlations and demonstration of the predominance of two mutations. 54 61 6
8044656 1994
33
Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker. 25 6
8308722 1993
34
Non-dystrophic myotonias and periodic paralyses. A European Neuromuscular Center Workshop held 4-6 October 1992, Ulm, Germany. 57 25
7689382 1993
35
Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita. 6 25
1316765 1992
36
Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita. 57 54 61
1315122 1992
37
Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH. 57 25
3587272 1987
38
Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands. 6 61
29606556 2018
39
Effects of S906T polymorphism on the severity of a novel borderline mutation I692M in Nav 1.4 cause periodic paralysis. 61 6
27714768 2017
40
Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement. 6 61
26256659 2015
41
Contractile abnormalities of mouse muscles expressing hyperkalemic periodic paralysis mutant NaV1.4 channels do not correlate with Na+ influx or channel content. 61 6
24714718 2014
42
Normokalemic periodic paralysis is not a distinct disease. 6 61
22926674 2012
43
Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome. 6 61
22914841 2012
44
Familial hyperkalemic periodic paralysis caused by a de novo mutation in the sodium channel gene SCN4A. 61 6
22253644 2011
45
A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis. 6 61
21881211 2011
46
Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy. 61 6
20076800 2009
47
Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness. 57 61
18317596 2008
48
Paralysis periodica paramyotonica caused by SCN4A Arg1448Cys mutation. 61 6
16801039 2006
49
Normokalemic periodic paralysis revisited: does it exist? 25 61 54
12210802 2002
50
The human skeletal muscle Na channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation. 61 6
11102465 2000

Variations for Hyperkalemic Periodic Paralysis

ClinVar genetic disease variations for Hyperkalemic Periodic Paralysis:

6 (show top 50) (show all 718)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SCN4A NM_000334.4(SCN4A):c.1333G>C (p.Val445Leu) SNV Pathogenic 448262 rs121908552 GRCh37: 17:62041947-62041947
GRCh38: 17:63964587-63964587
2 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4468T>C (p.Phe1490Leu) SNV Pathogenic 21158 rs80338790 GRCh37: 17:62019174-62019174
GRCh38: 17:63941814-63941814
3 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4442C>A (p.Ala1481Asp) SNV Pathogenic 576206 rs763893717 GRCh37: 17:62019200-62019200
GRCh38: 17:63941840-63941840
4 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2919del (p.Glu974fs) Deletion Pathogenic 645345 rs1567819905 GRCh37: 17:62026823-62026823
GRCh38: 17:63949463-63949463
5 SCN4A NM_000334.4(SCN4A):c.808C>A (p.Gln270Lys) SNV Pathogenic 657169 rs1597985462 GRCh37: 17:62045611-62045611
GRCh38: 17:63968251-63968251
6 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4307T>C (p.Leu1436Pro) SNV Pathogenic 661981 rs1598405334 GRCh37: 17:62019335-62019335
GRCh38: 17:63941975-63941975
7 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2614dup (p.Glu872fs) Duplication Pathogenic 851213 GRCh37: 17:62029022-62029023
GRCh38: 17:63951662-63951663
8 SCN4A NM_000334.4(SCN4A):c.703+1G>T SNV Pathogenic 931433 GRCh37: 17:62048521-62048521
GRCh38: 17:63971161-63971161
9 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2076C>G (p.Ile692Met) SNV Pathogenic 953362 GRCh37: 17:62034822-62034822
GRCh38: 17:63957462-63957462
10 SCN4A NM_000334.4(SCN4A):c.215dup (p.Pro73fs) Duplication Pathogenic 849707 GRCh37: 17:62049986-62049987
GRCh38: 17:63972626-63972627
11 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4372G>T (p.Val1458Phe) SNV Pathogenic 586519 rs1199222144 GRCh37: 17:62019270-62019270
GRCh38: 17:63941910-63941910
12 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3917G>A (p.Gly1306Glu) SNV Pathogenic 5920 rs80338792 GRCh37: 17:62021206-62021206
GRCh38: 17:63943846-63943846
13 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4364T>C (p.Ile1455Thr) SNV Pathogenic 932430 GRCh37: 17:62019278-62019278
GRCh38: 17:63941918-63941918
14 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3472C>T (p.Pro1158Ser) SNV Pathogenic 5917 rs121908555 GRCh37: 17:62022968-62022968
GRCh38: 17:63945608-63945608
15 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3395G>A (p.Arg1132Gln) SNV Pathogenic 21155 rs80338789 GRCh37: 17:62024451-62024451
GRCh38: 17:63947091-63947091
16 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3938C>T (p.Thr1313Met) SNV Pathogenic 5904 rs121908547 GRCh37: 17:62021185-62021185
GRCh38: 17:63943825-63943825
17 SCN4A NM_000334.4(SCN4A):c.1333G>A (p.Val445Met) SNV Pathogenic 5910 rs121908552 GRCh37: 17:62041947-62041947
GRCh38: 17:63964587-63964587
18 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3877G>A (p.Val1293Ile) SNV Pathogenic 5909 rs121908551 GRCh37: 17:62022068-62022068
GRCh38: 17:63944708-63944708
19 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3917G>T (p.Gly1306Val) SNV Pathogenic 5903 rs80338792 GRCh37: 17:62021206-62021206
GRCh38: 17:63943846-63943846
20 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3938C>T (p.Thr1313Met) SNV Pathogenic 5904 rs121908547 GRCh37: 17:62021185-62021185
GRCh38: 17:63943825-63943825
21 SCN4A NM_000334.4(SCN4A):c.1333G>A (p.Val445Met) SNV Pathogenic 5910 rs121908552 GRCh37: 17:62041947-62041947
GRCh38: 17:63964587-63964587
22 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4765G>A (p.Val1589Met) SNV Pathogenic 5905 rs121908548 GRCh37: 17:62018877-62018877
GRCh38: 17:63941517-63941517
23 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4428G>A (p.Met1476Ile) SNV Pathogenic 5921 rs121908559 GRCh37: 17:62019214-62019214
GRCh38: 17:63941854-63941854
24 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met) SNV Pathogenic 5896 rs80338957 GRCh37: 17:62034787-62034787
GRCh38: 17:63957427-63957427
25 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4774A>G (p.Met1592Val) SNV Pathogenic 5897 rs80338962 GRCh37: 17:62018868-62018868
GRCh38: 17:63941508-63941508
26 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2023C>T (p.Arg675Trp) SNV Pathogenic 5902 rs121908556 GRCh37: 17:62034875-62034875
GRCh38: 17:63957515-63957515
27 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2023C>G (p.Arg675Gly) SNV Pathogenic 5918 rs121908556 GRCh37: 17:62034875-62034875
GRCh38: 17:63957515-63957515
28 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2024G>A (p.Arg675Gln) SNV Pathogenic 5919 rs121908557 GRCh37: 17:62034874-62034874
GRCh38: 17:63957514-63957514
29 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2065C>A (p.Leu689Ile) SNV Pathogenic 21152 rs80338955 GRCh37: 17:62034833-62034833
GRCh38: 17:63957473-63957473
30 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2078T>C (p.Ile693Thr) SNV Pathogenic 5923 rs80338956 GRCh37: 17:62034820-62034820
GRCh38: 17:63957460-63957460
31 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3466G>A (p.Ala1156Thr) SNV Pathogenic 5900 rs80338958 GRCh37: 17:62022974-62022974
GRCh38: 17:63945614-63945614
32 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4483A>T (p.Ile1495Phe) SNV Pathogenic 21160 rs80338961 GRCh37: 17:62019159-62019159
GRCh38: 17:63941799-63941799
33 SCN4A NM_000334.4(SCN4A):c.2014C>G (p.Arg672Gly) SNV Pathogenic 5913 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
34 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2023C>G (p.Arg675Gly) SNV Pathogenic 5918 rs121908556 GRCh37: 17:62034875-62034875
GRCh38: 17:63957515-63957515
35 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4343G>C (p.Arg1448Pro) SNV Pathogenic 221263 rs121908545 GRCh37: 17:62019299-62019299
GRCh38: 17:63941939-63941939
36 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4342C>A (p.Arg1448Ser) SNV Pathogenic 221262 rs121908544 GRCh37: 17:62019300-62019300
GRCh38: 17:63941940-63941940
37 SCN4A NM_000334.4(SCN4A):c.2006G>A (p.Arg669His) SNV Pathogenic 5911 rs80338784 GRCh37: 17:62036638-62036638
GRCh38: 17:63959278-63959278
38 SCN4A NM_000334.4(SCN4A):c.2014C>T (p.Arg672Cys) SNV Pathogenic 21151 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
39 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4342C>T (p.Arg1448Cys) SNV Pathogenic 5898 rs121908544 GRCh37: 17:62019300-62019300
GRCh38: 17:63941940-63941940
40 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2023C>T (p.Arg675Trp) SNV Pathogenic 5902 rs121908556 GRCh37: 17:62034875-62034875
GRCh38: 17:63957515-63957515
41 SCN4A NM_000334.4(SCN4A):c.2015G>A (p.Arg672His) SNV Pathogenic 5912 rs80338788 GRCh37: 17:62036629-62036629
GRCh38: 17:63959269-63959269
42 SCN4A NM_000334.4(SCN4A):c.2014C>A (p.Arg672Ser) SNV Pathogenic 5916 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
43 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4343G>A (p.Arg1448His) SNV Pathogenic 5899 rs121908545 GRCh37: 17:62019299-62019299
GRCh38: 17:63941939-63941939
44 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2024G>A (p.Arg675Gln) SNV Pathogenic 5919 rs121908557 GRCh37: 17:62034874-62034874
GRCh38: 17:63957514-63957514
45 SCN4A NM_000334.4(SCN4A):c.1320T>G (p.Asn440Lys) SNV Pathogenic 221261 rs864622785 GRCh37: 17:62041960-62041960
GRCh38: 17:63964600-63964600
46 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3917G>C (p.Gly1306Ala) SNV Pathogenic 5908 rs80338792 GRCh37: 17:62021206-62021206
GRCh38: 17:63943846-63943846
47 SCN4A NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp) SNV Pathogenic 143199 rs527236148 GRCh37: 17:62048561-62048561
GRCh38: 17:63971201-63971201
48 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4774A>G (p.Met1592Val) SNV Pathogenic 5897 rs80338962 GRCh37: 17:62018868-62018868
GRCh38: 17:63941508-63941508
49 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met) SNV Pathogenic 5896 rs80338957 GRCh37: 17:62034787-62034787
GRCh38: 17:63957427-63957427
50 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3404G>A (p.Arg1135His) SNV Pathogenic 143201 rs527236150 GRCh37: 17:62024442-62024442
GRCh38: 17:63947082-63947082

UniProtKB/Swiss-Prot genetic disease variations for Hyperkalemic Periodic Paralysis:

72
# Symbol AA change Variation ID SNP ID
1 SCN4A p.Thr704Met VAR_001562 rs80338957
2 SCN4A p.Ala1156Thr VAR_001565 rs80338958
3 SCN4A p.Leu1433Arg VAR_001571 rs121908550
4 SCN4A p.Met1592Val VAR_001575 rs80338962
5 SCN4A p.Arg675Gly VAR_037104 rs121908556
6 SCN4A p.Arg675Gln VAR_037105 rs121908557
7 SCN4A p.Arg675Trp VAR_037106 rs121908556
8 SCN4A p.Arg1129Gln VAR_064987 rs527236149

Expression for Hyperkalemic Periodic Paralysis

Search GEO for disease gene expression data for Hyperkalemic Periodic Paralysis.

Pathways for Hyperkalemic Periodic Paralysis

Pathways related to Hyperkalemic Periodic Paralysis according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.34 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
2
Show member pathways
13.27 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
3
Show member pathways
12.58 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
4
Show member pathways
12.5 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
5
Show member pathways
12.45 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
6 12.42 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
7
Show member pathways
12.25 RYR1 KCNJ2 KCNJ18 CACNA1S
8
Show member pathways
11.83 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
9 11.38 SCN5A KCNJ2 KCNE3
10
Show member pathways
11.1 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
11 10.91 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
12 10.56 RYR1 CACNA1S

GO Terms for Hyperkalemic Periodic Paralysis

Cellular components related to Hyperkalemic Periodic Paralysis according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.4 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
2 integral component of membrane GO:0016021 10.28 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
3 plasma membrane GO:0005886 10.21 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
4 integral component of plasma membrane GO:0005887 10.06 SCN9A SCN4A SCN2A RYR1 PTPRZ1 KCNJ2
5 axon GO:0030424 9.88 SCN9A SCN8A SCN4A SCN2A SCN1A
6 Z disc GO:0030018 9.71 SCN8A SCN5A SCN1A RYR1
7 sarcolemma GO:0042383 9.69 SCN5A RYR1 CLCN1
8 I band GO:0031674 9.54 RYR1 CACNA1S
9 axon initial segment GO:0043194 9.5 SCN8A SCN1A NAV1
10 sodium channel complex GO:0034706 9.49 SCN2A SCN1A
11 intercalated disc GO:0014704 9.46 SCN5A SCN2A SCN1A KCNJ2
12 node of Ranvier GO:0033268 9.43 SCN8A SCN2A SCN1A
13 T-tubule GO:0030315 9.35 SCN5A SCN2A SCN1A KCNJ2 CACNA1S
14 voltage-gated sodium channel complex GO:0001518 9.1 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A

Biological processes related to Hyperkalemic Periodic Paralysis according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 10.06 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
2 ion transmembrane transport GO:0034220 9.92 SCN9A SCN8A SCN5A SCN2A SCN1A RYR1
3 sodium ion transport GO:0006814 9.91 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
4 cation transmembrane transport GO:0098655 9.85 SCN9A SCN8A SCN5A SCN2A SCN1A
5 sodium ion transmembrane transport GO:0035725 9.85 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
6 muscle contraction GO:0006936 9.8 SCN4A RYR1 CLCN1 CACNA1S
7 ion transport GO:0006811 9.77 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
8 neuronal action potential GO:0019228 9.73 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
9 cardiac conduction GO:0061337 9.7 SCN5A KCNJ2 CACNA1S
10 regulation of heart rate by cardiac conduction GO:0086091 9.69 SCN5A KCNJ2 KCNE3
11 cardiac muscle cell action potential involved in contraction GO:0086002 9.65 SCN5A SCN1A KCNJ2
12 membrane depolarization during action potential GO:0086010 9.63 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
13 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.59 SCN5A KCNE3
14 ventricular cardiac muscle cell action potential GO:0086005 9.58 SCN5A KCNE3
15 regulation of cardiac muscle cell contraction GO:0086004 9.58 SCN5A KCNJ2
16 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.57 SCN5A KCNJ2
17 cellular response to caffeine GO:0071313 9.56 RYR1 CACNA1S
18 membrane repolarization during action potential GO:0086011 9.55 KCNJ2 KCNE3
19 neuronal action potential propagation GO:0019227 9.54 SCN1A CLCN1
20 regulation of ion transmembrane transport GO:0034765 9.36 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A

Molecular functions related to Hyperkalemic Periodic Paralysis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cation channel activity GO:0005261 9.8 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
2 sodium channel activity GO:0005272 9.73 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
3 voltage-gated sodium channel activity GO:0005248 9.63 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
4 ion channel activity GO:0005216 9.61 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A
5 inward rectifier potassium channel activity GO:0005242 9.37 KCNJ2 KCNJ18
6 voltage-gated ion channel activity GO:0005244 9.36 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1A

Sources for Hyperkalemic Periodic Paralysis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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