HOKPP1
MCID: HYP370
MIFTS: 64

Hypokalemic Periodic Paralysis, Type 1 (HOKPP1)

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

Aliases & Classifications for Hypokalemic Periodic Paralysis, Type 1

MalaCards integrated aliases for Hypokalemic Periodic Paralysis, Type 1:

Name: Hypokalemic Periodic Paralysis, Type 1 57 13
Hypokalemic Periodic Paralysis 57 12 73 25 20 43 58 36 29 54 6 44 15 70
Hokpp 57 25 20 43 72
Hypopp 25 20 43 72
Westphall Disease 43 58 72
Familial Hypokalemic Periodic Paralysis 12 43
Hypokalemic Periodic Paralysis Type 1 73 70
Hypokalemic Periodic Paralysis 1 29 6
Familial Periodic Paralysis 12 70
Westphal Disease 12 70
Hokpp1 57 72
Paralysis, Hypokalemic, Periodic, Type 1 39
Hypokalemic Familial Periodic Paralysis 12
Primary Hypokalemic Periodic Paralysis 43
Hypokalemic Periodic Paralysis; Hokpp 57
Periodic Paralysis Hypokalemic 1 72
Paralysis, Hypokalemic, Periodic 39
Periodic Hypokalemic Paralysis 12
Periodic Paralysis I 12
Hypokpp 43

Characteristics:

Orphanet epidemiological data:

58
hypokalemic periodic paralysis
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
allelic disorder to hyperkalemic periodic paralysis (hypp, )
onset usually in second decade (may occur earlier)
one-third of cases are sporadic
reduced penetrance in females


HPO:

31
hypokalemic periodic paralysis, type 1:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


GeneReviews:

25
Penetrance In general, the penetrance of this disorder is high (≥90%) in males and reduced in females. an exception to this occurs with pathogenic variants with an arginine-to-glycine substitution for which high penetrance in males and females is noted [kim et al 2005, wang et al 2005, winczewska-wiktor et al 2007].

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:14452
OMIM® 57 170400
KEGG 36 H00746
MeSH 44 D020514
NCIt 50 C84775
SNOMED-CT 67 240093008
ICD10 32 G72.3
MESH via Orphanet 45 D020514
ICD10 via Orphanet 33 G72.3
UMLS via Orphanet 71 C0238357 C0238358
Orphanet 58 ORPHA681
UMLS 70 C0030443 C0238358 C1279186 more

Summaries for Hypokalemic Periodic Paralysis, Type 1

MedlinePlus Genetics : 43 Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, some develop persistent muscle weakness later in life.People with hypokalemic periodic paralysis typically have reduced levels of potassium in their blood (hypokalemia) during episodes of muscle weakness. Researchers are investigating how low potassium levels may be related to the muscle abnormalities in this condition.

MalaCards based summary : Hypokalemic Periodic Paralysis, Type 1, also known as hypokalemic periodic paralysis, is related to thyrotoxic periodic paralysis and hypokalemic periodic paralysis, type 2, and has symptoms including muscle weakness, myalgia and sciatica. An important gene associated with Hypokalemic Periodic Paralysis, Type 1 is CACNA1S (Calcium Voltage-Gated Channel Subunit Alpha1 S), and among its related pathways/superpathways are MAPK signaling pathway and Calcium signaling pathway. The drugs Dichlorphenamide and Hops have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, thyroid and smooth muscle, and related phenotypes are periodic hypokalemic paresis and episodic hypokalemia

GARD : 20 Hypokalemic periodic paralysis (HOKPP) is characterized by episodes of muscle paralysis associated with a fall in blood potassium levels ( hypokalemia ). Episodes typically involve a temporary inability to move muscles in the arms and legs. The first attack usually occurs in childhood or adolescence. Attacks can last for hours or days, and the frequency of attacks varies among people with HOKPP. The frequency is usually highest between the ages of 15 and 35, and then decreases with age. Some people with HOKPP also develop late-onset proximal myopathy. HOKPP can be caused by mutations in the CACNA1S, SCN4A, or KCNJ18 gene. Inheritance is autosomal dominant. Treatment varies depending on the intensity and duration of attacks. Minor attacks may go away on their own, while treatment for moderate or severe attacks may involve taking potassium salts or intravenous (IV) potassium.

OMIM® : 57 There are 2 dominantly inherited, clinically similar types of episodic flaccid generalized weakness, HOKPP and HYPP, that are distinguished by the changes in serum potassium levels during paralytic attacks. In contrast to HYPP, myotonia is usually not present in HOKPP (Jurkat-Rott et al., 2000). Hypokalemic periodic paralysis may also occur as a rare complication of thyrotoxicosis (see TTPP1, 188580), a disorder with a high frequency in individuals of Asian descent (Kung, 2006). (170400) (Updated 05-Apr-2021)

KEGG : 36 Hypokalemic periodic paralysis (HypoPP) is a member of periodic paralyses, an autosomal dominant genetic disorders caused by mutations in the sodium, potassium, and calcium channel genes in skeletal muscle. In general, HypoPP is characterized by reversible attacks of muscle weakness concomitant with decreased blood potassium concentrations. HypoPP is associated with point mutations in both CACNA1S (HypoPP1) and SCN4A (HypoPP2).

UniProtKB/Swiss-Prot : 72 Periodic paralysis hypokalemic 1: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.

Wikipedia : 73 Hypokalemic periodic paralysis (hypoKPP), also known as familial hypokalemic periodic paralysis (FHPP),... more...

GeneReviews: NBK1338

Related Diseases for Hypokalemic Periodic Paralysis, Type 1

Diseases in the Hypokalemic Periodic Paralysis, Type 1 family:

Hypokalemic Periodic Paralysis, Type 2

Diseases related to Hypokalemic Periodic Paralysis, Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 196)
# Related Disease Score Top Affiliating Genes
1 thyrotoxic periodic paralysis 33.2 SCN4A KCNJ2 KCNJ18 CACNA1S
2 hypokalemic periodic paralysis, type 2 33.1 SCN7A SCN4A QDPR GH-LCR
3 thyrotoxic periodic paralysis 1 32.7 KCNJ18 CACNA1S
4 periodic paralyses 32.4 SCN4A KCNJ2 KCNE3 GH-LCR CACNA1S
5 graves disease 1 31.8 SCN4A KCNJ18 INS CACNA1S
6 hypokalemia 31.7 SLC12A3 SCN4A KCNJ18 INS CACNA1S CACNA1D
7 myotonia 31.4 SCN7A SCN4A GH-LCR CLCN1
8 myopathy 31.1 STAC3 SCN4A RYR1 INS GH-LCR CLCN1
9 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 30.9 RYR1 GH-LCR CACNA1S
10 periodic paralysis 30.9 SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
11 hyperkalemic periodic paralysis 30.9 SCN5A SCN4A RYR1 NAV1 KCNJ2 KCNJ18
12 malignant hyperthermia 30.7 STAC3 SCN7A SCN5A SCN4A RYR1 QDPR
13 myotonia congenita 30.7 SCN4A KCNJ2 GH-LCR CLCN1 CACNA1S
14 normokalemic periodic paralysis 30.7 SCN7A SCN4A GH-LCR
15 malignant hyperthermia susceptibility 30.6 STAC3 SCN4A RYR1 CACNA1S
16 neuromuscular disease 30.5 STAC3 SCN5A SCN4A RYR1 CLCN1 CACNA1S
17 familial periodic paralysis 30.5 TMEM266 STAC3 SLC12A3 SCN5A SCN4A RYR1
18 myotonic disease 30.5 SCN4A RYR1 CLCN1
19 andersen cardiodysrhythmic periodic paralysis 30.4 SCN5A SCN4A KCNJ2 KCNJ18 KCNJ12 KCNE3
20 bartter disease 30.4 SLC12A3 KCNJ18 KCNJ12 CLCN1
21 isolated elevated serum creatine phosphokinase levels 30.3 SCN5A SCN4A RYR1 KCNJ12 CLCN1 CACNA1C
22 ventricular fibrillation, paroxysmal familial, 1 30.3 SCN5A CACNA1C
23 paramyotonia congenita of von eulenburg 30.2 SCN5A SCN4A RYR1 NAV1 KCNJ2 KCNJ18
24 long qt syndrome 29.8 SCN5A SCN4A NAV1 KCNJ2 KCNJ12 KCNE3
25 thyrotoxic periodic paralysis 2 11.6
26 familial periodic paralyses 11.3
27 wolff-parkinson-white syndrome 11.3
28 hyperthyroidism 10.9
29 graves' disease 10.7
30 myotonia, potassium-aggravated 10.7
31 renal tubular acidosis 10.7
32 malignant hyperthermia 5 10.6
33 distal renal tubular acidosis 10.6
34 hypothyroidism 10.5
35 quadriplegia 10.5
36 myasthenia gravis 10.4
37 sjogren syndrome 10.4
38 metabolic acidosis 10.4
39 goiter 10.4
40 hyperinsulinism 10.4
41 adenoma 10.4
42 neuropathy, hereditary sensory and autonomic, type vii 10.4 SCN4A CACNA1S
43 atrophic muscular disease 10.4 RYR1 CLCN1
44 brugada syndrome 6 10.4 SCN5A KCNE3
45 episodic ataxia 10.4 SCN4A GH-LCR CACNA1S
46 idiopathic ventricular fibrillation, non brugada type 10.4 SCN5A CACNA1C
47 uvulitis 10.4 KCNJ18 INS
48 thyroiditis 10.4
49 right bundle branch block 10.4 SCN5A KCNE3 CACNA1C
50 polyglucosan body myopathy 1 with or without immunodeficiency 10.4 SLC12A3 SCN4A RYR1

Graphical network of the top 20 diseases related to Hypokalemic Periodic Paralysis, Type 1:



Diseases related to Hypokalemic Periodic Paralysis, Type 1

Symptoms & Phenotypes for Hypokalemic Periodic Paralysis, Type 1

Human phenotypes related to Hypokalemic Periodic Paralysis, Type 1:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 periodic hypokalemic paresis 58 31 obligate (100%) Obligate (100%) HP:0008153
2 episodic hypokalemia 58 31 obligate (100%) Obligate (100%) HP:0012726
3 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
4 episodic flaccid weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003752
5 mildly elevated creatine kinase 58 31 hallmark (90%) Very frequent (99-80%) HP:0008180
6 increased intramyocellular lipid droplets 58 31 hallmark (90%) Very frequent (99-80%) HP:0012240
7 exercise-induced muscle fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0009020
8 postprandial hyperglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0011998
9 late-onset proximal muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003694
10 myopathy 31 occasional (7.5%) HP:0003198
11 respiratory paralysis 58 31 very rare (1%) Very rare (<4-1%) HP:0002203
12 adrenocortical adenoma 58 31 very rare (1%) Very rare (<4-1%) HP:0008256
13 fatigable weakness of respiratory muscles 58 31 very rare (1%) Very rare (<4-1%) HP:0030196
14 hypokalemia 31 HP:0002900
15 myotonia 58 Excluded (0%)
16 abnormality of muscle fibers 58 Very frequent (99-80%)
17 paralysis 58 Very frequent (99-80%)
18 impaired myocardial contractility 58 Excluded (0%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Muscle Soft Tissue:
flaccid weakness or paralysis, episodic attacks
attacks last 4 to 24 hours
attacks precipitated by hypokalemia, administration of glucose or insulin, heavy carbohydrate consumption, stress, fatigue, rest after exercise
attacks may present during or after sleep
attacks relieved by potassium administration
more
Laboratory Abnormalities:
hypokalemia occurs during paralytic attacks

Clinical features from OMIM®:

170400 (Updated 05-Apr-2021)

UMLS symptoms related to Hypokalemic Periodic Paralysis, Type 1:


muscle weakness; myalgia; sciatica; muscle cramp; muscle rigidity; muscle spasticity

MGI Mouse Phenotypes related to Hypokalemic Periodic Paralysis, Type 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.93 CACNA1C CACNA1D CACNA1F CACNA1S INS KCNE3
2 muscle MP:0005369 9.61 CACNA1C CACNA1S CLCN1 INS KCNJ2 RYR1
3 respiratory system MP:0005388 9.17 CACNA1S KCNE3 KCNJ2 RYR1 SCN4A SCN5A

Drugs & Therapeutics for Hypokalemic Periodic Paralysis, Type 1

Drugs for Hypokalemic Periodic Paralysis, Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# 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 Carbonic Anhydrase Inhibitors Phase 3
4
Bumetanide Approved Phase 2 28395-03-1 2471
5 Sodium Potassium Chloride Symporter Inhibitors Phase 2
6 diuretics Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders Completed NCT00004802 Phase 3 dichlorphenamide
2 Dichlorphenamide vs. Placebo for Periodic Paralysis Completed NCT00494507 Phase 3 Dichlorphenamide (double-blind);Placebo (double-blind);Dichlorphenamide (open-label)
3 A Randomised, Double-blind, Placebo-controlled, Phase II Clinical Trial With a Cross-over Design Assessing Efficacy of a Single Dose of Bumetanide in Reducing Focal Attack Severity in Hypokalaemic Periodic Paralysis Assessed Using the McManis Protocol Terminated NCT02582476 Phase 2 Bumetanide;Placebo

Search NIH Clinical Center for Hypokalemic Periodic Paralysis, Type 1

Cochrane evidence based reviews: hypokalemic periodic paralysis

Genetic Tests for Hypokalemic Periodic Paralysis, Type 1

Genetic tests related to Hypokalemic Periodic Paralysis, Type 1:

# Genetic test Affiliating Genes
1 Hypokalemic Periodic Paralysis 29
2 Hypokalemic Periodic Paralysis 1 29 CACNA1S SCN4A

Anatomical Context for Hypokalemic Periodic Paralysis, Type 1

MalaCards organs/tissues related to Hypokalemic Periodic Paralysis, Type 1:

40
Skeletal Muscle, Thyroid, Smooth Muscle, Pituitary, Brain

Publications for Hypokalemic Periodic Paralysis, Type 1

Articles related to Hypokalemic Periodic Paralysis, Type 1:

(show top 50) (show all 691)
# Title Authors PMID Year
1
Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. 25 57 6 54 61
10944223 2000
2
Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. 57 6 54 61
19118277 2009
3
Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene. 6 25 57
18835861 2008
4
Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK. 54 6 61 57
11591859 2001
5
Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family. 6 54 61 25
15726306 2005
6
Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. 61 6 57
8004673 1994
7
Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy. 6 61 25
28012042 2017
8
Genotype and phenotype analysis of patients with sporadic periodic paralysis. 61 6 25
21841462 2012
9
Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia. 61 6 25
21490317 2011
10
K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks. 6 25 61
19225109 2009
11
Myopathy as the first symptom of hypokalemic periodic paralysis--case report of a girl from a Polish family with CACNA1S (R1239G) mutation. 6 25 61
18229654 2007
12
A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G). 61 6 25
15716625 2005
13
Correlating phenotype and genotype in the periodic paralyses. 57 25 61
15534250 2004
14
Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis. 6 57
7897626 1995
15
Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family. 61 6 54
19779499 2009
16
Gating pore current in an inherited ion channelopathy. 57 25
17330043 2007
17
Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis. 6 61 54
16890191 2006
18
Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. 61 6 54
14557559 2003
19
Enhanced inactivation and pH sensitivity of Na(+) channel mutations causing hypokalaemic periodic paralysis type II. 25 6
11912116 2002
20
Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. 57 25
11353725 2001
21
A novel sodium channel mutation in a family with hypokalemic periodic paralysis. 61 6 54
10599760 1999
22
Identification of mutations in the CACNL1A3 gene in 13 families of Scandinavian origin having hypokalemic periodic paralysis and evidence of a founder effect in Danish families. 6 54 61
9066893 1997
23
Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families. 6 54 61
7847370 1995
24
A calcium channel mutant mouse model of hypokalemic periodic paralysis. 61 6
23187123 2012
25
The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis. 61 6
18162704 2007
26
Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge. 61 57
16608889 2006
27
Thyrotoxic periodic paralysis associated with a mutation in the sodium channel gene SCN4A. 25 61 54
15645704 2004
28
SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide. 61 6
15557532 2004
29
Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis. 61 54 25
15072700 2004
30
Muscle weakness in a Japanese family of Arg1239His mutation hypokalemic periodic paralysis. 61 6
11555352 2001
31
Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis. 61 6
11558801 2001
32
[A case of familial hypokalemic periodic paralysis with hyperuricemia during paralytic attack and genetic analysis of the pedigree]. 61 6
11808349 2001
33
Clinical-molecular study of a family with essential tremor, late onset seizures and periodic paralysis. 6 61
11034874 2000
34
Muscle fiber conduction velocity in arg1239his mutation in hypokalemic periodic paralysis. 6 61
10639629 2000
35
Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis. 61 6
10074484 1999
36
Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H. 61 6
9852570 1998
37
Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor alpha1 subunits (R528H) 6 61
9512357 1998
38
Genetic heterogeneity in hypokalemic periodic paralysis (hypoPP). 57 61
7959693 1994
39
A calcium channel mutation causing hypokalemic periodic paralysis. 61 6
7987325 1994
40
Diagnosis of familial hypokalemic periodic paralysis: role of the potassium exercise test. 61 57
1436528 1992
41
Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci. 61 57
1330884 1992
42
Different gene loci for hyperkalemic and hypokalemic periodic paralysis. 61 57
1822800 1991
43
Hypokalemic periodic paralysis due to the Sjögren syndrome in Chinese patients. 61 57
2916810 1989
44
Familial hypokalemic periodic paralysis. 50-year follow-up of a large family. 61 57
3855357 1985
45
Hypokalemic periodic paralysis in Sjögren's syndrome. 57 61
7305577 1981
46
Erythrocyte membrane studies in familial hypokalemic periodic paralysis. 61 57
150837 1978
47
Familial hypokalemic periodic paralysis in blacks. 57 61
1147439 1975
48
Familial hypokalemic periodic paralysis. 57 61
4834972 1974
49
A Reliable Targeted Next-Generation Sequencing Strategy for Diagnosis of Myopathies and Muscular Dystrophies, Especially for the Giant Titin and Nebulin Genes. 6
29792937 2018
50
When muscle Ca2+ channels carry monovalent cations through gating pores: insights into the pathophysiology of type 1 hypokalaemic periodic paralysis. 6
29572832 2018

Variations for Hypokalemic Periodic Paralysis, Type 1

ClinVar genetic disease variations for Hypokalemic Periodic Paralysis, Type 1:

6 (show top 50) (show all 1030)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CACNA1S NM_000069.3(CACNA1S):c.1582C>G (p.Arg528Gly) SNV Pathogenic 21034 rs80338778 GRCh37: 1:201047044-201047044
GRCh38: 1:201077916-201077916
2 CACNA1S NM_000069.3(CACNA1S):c.3526-2A>G SNV Pathogenic 209137 rs797045031 GRCh37: 1:201027621-201027621
GRCh38: 1:201058493-201058493
3 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3472C>T (p.Pro1158Ser) SNV Pathogenic 5917 rs121908555 GRCh37: 17:62022968-62022968
GRCh38: 17:63945608-63945608
4 CACNA1S NM_000069.3(CACNA1S):c.3715C>G (p.Arg1239Gly) SNV Pathogenic 17624 rs28930069 GRCh37: 1:201022667-201022667
GRCh38: 1:201053539-201053539
5 CACNA1S NM_000069.3(CACNA1S):c.2691G>T (p.Arg897Ser) SNV Pathogenic 17630 rs80338779 GRCh37: 1:201035411-201035411
GRCh38: 1:201066283-201066283
6 CACNA1S NM_000069.3(CACNA1S):c.1503C>A (p.Cys501Ter) SNV Pathogenic 473964 rs762294904 GRCh37: 1:201047123-201047123
GRCh38: 1:201077995-201077995
7 CACNA1S NM_000069.3(CACNA1S):c.564del (p.Ile189fs) Deletion Pathogenic 541039 rs1553252746 GRCh37: 1:201060898-201060898
GRCh38: 1:201091770-201091770
8 CACNA1S NM_000069.3(CACNA1S):c.1796del (p.Asn599fs) Deletion Pathogenic 567517 rs1558071742 GRCh37: 1:201046079-201046079
GRCh38: 1:201076951-201076951
9 CACNA1S NM_000069.3(CACNA1S):c.3715C>G (p.Arg1239Gly) SNV Pathogenic 17624 rs28930069 GRCh37: 1:201022667-201022667
GRCh38: 1:201053539-201053539
10 CACNA1S NM_000069.3(CACNA1S):c.4025C>A (p.Ser1342Ter) SNV Pathogenic 641633 rs563795648 GRCh37: 1:201020200-201020200
GRCh38: 1:201051072-201051072
11 CACNA1S NM_000069.3(CACNA1S):c.2970G>A (p.Trp990Ter) SNV Pathogenic 643605 rs1572035834 GRCh37: 1:201031155-201031155
GRCh38: 1:201062027-201062027
12 CACNA1S NM_000069.3(CACNA1S):c.732del (p.Cys245fs) Deletion Pathogenic 646905 rs1558079311 GRCh37: 1:201058554-201058554
GRCh38: 1:201089426-201089426
13 CACNA1S NM_000069.3(CACNA1S):c.897C>G (p.Tyr299Ter) SNV Pathogenic 649853 rs1572059904 GRCh37: 1:201058389-201058389
GRCh38: 1:201089261-201089261
14 CACNA1S NM_000069.3(CACNA1S):c.2812del (p.Leu938fs) Deletion Pathogenic 656431 rs1572038993 GRCh37: 1:201035007-201035007
GRCh38: 1:201065879-201065879
15 CACNA1S NM_000069.3(CACNA1S):c.5104C>T (p.Arg1702Ter) SNV Pathogenic 402469 rs550371466 GRCh37: 1:201010662-201010662
GRCh38: 1:201041534-201041534
16 CACNA1S NM_000069.3(CACNA1S):c.1847G>A (p.Trp616Ter) SNV Pathogenic 665684 rs1572048220 GRCh37: 1:201044724-201044724
GRCh38: 1:201075596-201075596
17 CACNA1S NM_000069.3(CACNA1S):c.4871_4874del (p.Asn1624fs) Deletion Pathogenic 665842 rs1572019465 GRCh37: 1:201012583-201012586
GRCh38: 1:201043455-201043458
18 CACNA1S NM_000069.3(CACNA1S):c.4947del (p.Asp1650fs) Deletion Pathogenic 848766 GRCh37: 1:201012510-201012510
GRCh38: 1:201043382-201043382
19 CACNA1S NM_000069.3(CACNA1S):c.3025_3026del (p.Thr1009fs) Deletion Pathogenic 862482 GRCh37: 1:201031099-201031100
GRCh38: 1:201061971-201061972
20 CACNA1S NM_000069.3(CACNA1S):c.19C>T (p.Gln7Ter) SNV Pathogenic 854887 GRCh37: 1:201081449-201081449
GRCh38: 1:201112321-201112321
21 CACNA1S NM_000069.3(CACNA1S):c.3773G>A (p.Trp1258Ter) SNV Pathogenic 856306 GRCh37: 1:201022609-201022609
GRCh38: 1:201053481-201053481
22 CACNA1S NM_000069.3(CACNA1S):c.2691G>T (p.Arg897Ser) SNV Pathogenic 17630 rs80338779 GRCh37: 1:201035411-201035411
GRCh38: 1:201066283-201066283
23 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3395G>A (p.Arg1132Gln) SNV Pathogenic 21155 rs80338789 GRCh37: 17:62024451-62024451
GRCh38: 17:63947091-63947091
24 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3395G>A (p.Arg1132Gln) SNV Pathogenic 21155 rs80338789 GRCh37: 17:62024451-62024451
GRCh38: 17:63947091-63947091
25 CACNA1S NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His) SNV Pathogenic 17623 rs28930068 GRCh37: 1:201022666-201022666
GRCh38: 1:201053538-201053538
26 CACNA1S NM_000069.3(CACNA1S):c.1583G>A (p.Arg528His) SNV Pathogenic 17625 rs80338777 GRCh37: 1:201047043-201047043
GRCh38: 1:201077915-201077915
27 CACNA1S NM_000069.3(CACNA1S):c.3414+3A>T SNV Pathogenic 381082 rs892742196 GRCh37: 1:201029783-201029783
GRCh38: 1:201060655-201060655
28 CACNA1S NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His) SNV Pathogenic 17623 rs28930068 GRCh37: 1:201022666-201022666
GRCh38: 1:201053538-201053538
29 CACNA1S NM_000069.3(CACNA1S):c.1583G>A (p.Arg528His) SNV Pathogenic 17625 rs80338777 GRCh37: 1:201047043-201047043
GRCh38: 1:201077915-201077915
30 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3938C>T (p.Thr1313Met) SNV Pathogenic 5904 rs121908547 GRCh37: 17:62021185-62021185
GRCh38: 17:63943825-63943825
31 SCN4A NM_000334.4(SCN4A):c.1333G>A (p.Val445Met) SNV Pathogenic 5910 rs121908552 GRCh37: 17:62041947-62041947
GRCh38: 17:63964587-63964587
32 CACNA1S NM_000069.3(CACNA1S):c.502C>T (p.Arg168Ter) SNV Pathogenic 504167 rs201998231 GRCh37: 1:201061139-201061139
GRCh38: 1:201092011-201092011
33 CACNA1S NM_000069.3(CACNA1S):c.4797+1G>A SNV Pathogenic 998344 GRCh37: 1:201013455-201013455
GRCh38: 1:201044327-201044327
34 SCN4A NM_000334.4(SCN4A):c.2006G>A (p.Arg669His) SNV Pathogenic 5911 rs80338784 GRCh37: 17:62036638-62036638
GRCh38: 17:63959278-63959278
35 SCN4A NM_000334.4(SCN4A):c.2015G>A (p.Arg672His) SNV Pathogenic 5912 rs80338788 GRCh37: 17:62036629-62036629
GRCh38: 17:63959269-63959269
36 SCN4A NM_000334.4(SCN4A):c.2014C>G (p.Arg672Gly) SNV Pathogenic 5913 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
37 SCN4A NM_000334.4(SCN4A):c.2014C>A (p.Arg672Ser) SNV Pathogenic 5916 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
38 CACNA1S NM_000069.3(CACNA1S):c.2627T>A (p.Val876Glu) SNV Pathogenic 17631 rs267606698 GRCh37: 1:201036045-201036045
GRCh38: 1:201066917-201066917
39 SCN4A NM_000334.4(SCN4A):c.2006G>A (p.Arg669His) SNV Pathogenic 5911 rs80338784 GRCh37: 17:62036638-62036638
GRCh38: 17:63959278-63959278
40 SCN4A NM_000334.4(SCN4A):c.2014C>A (p.Arg672Ser) SNV Pathogenic 5916 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
41 SCN4A NM_000334.4(SCN4A):c.2014C>G (p.Arg672Gly) SNV Pathogenic 5913 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
42 SCN4A NM_000334.4(SCN4A):c.2014C>T (p.Arg672Cys) SNV Pathogenic 21151 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
43 SCN4A NM_000334.4(SCN4A):c.2015G>A (p.Arg672His) SNV Pathogenic 5912 rs80338788 GRCh37: 17:62036629-62036629
GRCh38: 17:63959269-63959269
44 CACNA1S NM_000069.3(CACNA1S):c.2748C>G (p.His916Gln) SNV Pathogenic 143198 rs2297902 GRCh37: 1:201035071-201035071
GRCh38: 1:201065943-201065943
45 SCN4A NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp) SNV Pathogenic 143199 rs527236148 GRCh37: 17:62048561-62048561
GRCh38: 17:63971201-63971201
46 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3404G>A (p.Arg1135His) SNV Pathogenic 143201 rs527236150 GRCh37: 17:62024442-62024442
GRCh38: 17:63947082-63947082
47 CACNA1S NM_000069.3(CACNA1S):c.3428C>A (p.Ser1143Ter) SNV Pathogenic 1033625 GRCh37: 1:201028414-201028414
GRCh38: 1:201059286-201059286
48 CACNA1S NM_000069.3(CACNA1S):c.5049-2A>G SNV Pathogenic 541072 rs148989517 GRCh37: 1:201010719-201010719
GRCh38: 1:201041591-201041591
49 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4774A>G (p.Met1592Val) SNV Pathogenic 5897 rs80338962 GRCh37: 17:62018868-62018868
GRCh38: 17:63941508-63941508
50 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met) SNV Pathogenic 5896 rs80338957 GRCh37: 17:62034787-62034787
GRCh38: 17:63957427-63957427

UniProtKB/Swiss-Prot genetic disease variations for Hypokalemic Periodic Paralysis, Type 1:

72
# Symbol AA change Variation ID SNP ID
1 CACNA1S p.Arg528His VAR_001499 rs80338777
2 CACNA1S p.Arg1239Gly VAR_001501 rs28930069
3 CACNA1S p.Arg1239His VAR_001502 rs28930068
4 CACNA1S p.Arg528Gly VAR_054953 rs80338778
5 CACNA1S p.Arg900Ser VAR_054954

Expression for Hypokalemic Periodic Paralysis, Type 1

Search GEO for disease gene expression data for Hypokalemic Periodic Paralysis, Type 1.

Pathways for Hypokalemic Periodic Paralysis, Type 1

Pathways related to Hypokalemic Periodic Paralysis, Type 1 according to KEGG:

36
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Calcium signaling pathway hsa04020
3 Cardiac muscle contraction hsa04260
4 Vascular smooth muscle contraction hsa04270
5 Cholinergic synapse hsa04725
6 GABAergic synapse hsa04727
7 GnRH signaling pathway hsa04912

Pathways related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

(show all 44)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.5 SCN7A SCN5A SCN4A RYR1 CLCN1 CACNA1S
2
Show member pathways
13.45 SCN7A SCN5A SCN4A INS CACNA1S CACNA1D
3
Show member pathways
12.97 SCN7A SCN5A SCN4A CACNA1S CACNA1F CACNA1D
4
Show member pathways
12.84 INS CACNA1S CACNA1F CACNA1D CACNA1C
5
Show member pathways
12.77 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
6
Show member pathways
12.75 RYR1 INS CACNA1S CACNA1D CACNA1C
7 12.71 INS CACNA1S CACNA1F CACNA1D CACNA1C
8
Show member pathways
12.64 RYR1 KCNJ2 KCNJ18 KCNJ12 CACNA1S CACNA1F
9
Show member pathways
12.62 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
10
Show member pathways
12.61 SLC12A3 SCN7A SCN5A SCN4A CLCN1
11
Show member pathways
12.57 CACNA1S CACNA1F CACNA1D CACNA1C
12
Show member pathways
12.5 CACNA1S CACNA1F CACNA1D CACNA1C
13
Show member pathways
12.48 RYR1 CACNA1S CACNA1D CACNA1C
14
Show member pathways
12.48 SCN7A SCN5A INS CACNA1S CACNA1F CACNA1D
15
Show member pathways
12.46 RYR1 CACNA1S CACNA1D CACNA1C
16
Show member pathways
12.42 SCN7A SCN5A SCN4A RYR1 KCNJ2 KCNJ12
17 12.35 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
18 12.28 CACNA1S CACNA1F CACNA1D CACNA1C
19
Show member pathways
12.26 CACNA1S CACNA1F CACNA1D CACNA1C
20
Show member pathways
12.22 RYR1 KCNJ2 KCNJ18 KCNJ12 CACNA1S CACNA1F
21
Show member pathways
12.2 CACNA1S CACNA1F CACNA1D CACNA1C
22 12.16 KCNJ2 KCNJ12 KCNE3 CACNA1S CACNA1F CACNA1D
23 12.1 CACNA1S CACNA1F CACNA1D CACNA1C
24 12.09 CACNA1S CACNA1F CACNA1D CACNA1C
25 12.04 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
26
Show member pathways
12.01 CACNA1S CACNA1F CACNA1D CACNA1C
27
Show member pathways
11.96 SCN7A SCN5A SCN4A
28
Show member pathways
11.95 INS CLCN1 CACNA1S CACNA1D CACNA1C
29 11.94 CACNA1S CACNA1F CACNA1D CACNA1C
30
Show member pathways
11.82 INS CACNA1D CACNA1C
31 11.79 CACNA1S CACNA1F CACNA1D CACNA1C
32 11.67 CACNA1S CACNA1F CACNA1D CACNA1C
33 11.64 KCNJ2 CACNA1S CACNA1F CACNA1D CACNA1C
34 11.63 CACNA1S CACNA1F CACNA1D CACNA1C
35 11.57 CACNA1S CACNA1F CACNA1D CACNA1C
36 11.47 RYR1 CACNA1S CACNA1D CACNA1C
37 11.47 SCN5A KCNJ2 KCNE3 CACNA1D CACNA1C
38 11.35 CACNA1S CACNA1D CACNA1C
39 11.24 SCN7A SCN5A SCN4A
40
Show member pathways
11.1 SCN7A SCN5A SCN4A KCNE3 CACNA1S CACNA1F
41 11.05 CACNA1D CACNA1C
42 10.99 CACNA1F CACNA1D CACNA1C
43 10.74 CACNA1D CACNA1C
44 10.74 RYR1 CACNA1S

GO Terms for Hypokalemic Periodic Paralysis, Type 1

Cellular components related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.38 TMEM266 STAC3 SLC12A3 SCN7A SCN5A SCN4A
2 integral component of membrane GO:0016021 10.28 TMEM266 SLC12A3 SCN7A SCN5A SCN4A RYR1
3 plasma membrane GO:0005886 10.06 TMEM266 STAC3 SLC12A3 SCN7A SCN5A SCN4A
4 integral component of plasma membrane GO:0005887 10.04 TMEM266 SLC12A3 SCN4A RYR1 KCNJ2 CLCN1
5 perikaryon GO:0043204 9.76 TMEM266 KCNE3 CACNA1F CACNA1C
6 Z disc GO:0030018 9.73 SCN5A RYR1 CACNA1D CACNA1C
7 sarcolemma GO:0042383 9.65 STAC3 SCN5A RYR1 CLCN1 CACNA1C
8 voltage-gated sodium channel complex GO:0001518 9.54 SCN7A SCN5A SCN4A
9 I band GO:0031674 9.52 RYR1 CACNA1S
10 intrinsic component of membrane GO:0031224 9.51 KCNJ2 KCNJ12
11 L-type voltage-gated calcium channel complex GO:1990454 9.5 CACNA1S CACNA1D CACNA1C
12 T-tubule GO:0030315 9.35 STAC3 SCN5A KCNJ2 CACNA1S CACNA1C
13 voltage-gated calcium channel complex GO:0005891 9.02 STAC3 CACNA1S CACNA1F CACNA1D CACNA1C

Biological processes related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

(show all 31)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 10 TMEM266 SLC12A3 SCN7A SCN5A SCN4A RYR1
2 ion transmembrane transport GO:0034220 9.97 SCN7A SCN5A RYR1 CLCN1 CACNA1D
3 calcium ion transport GO:0006816 9.91 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
4 calcium ion transmembrane transport GO:0070588 9.89 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
5 potassium ion transport GO:0006813 9.88 KCNJ2 KCNJ18 KCNJ12 KCNE3
6 sodium ion transport GO:0006814 9.88 SLC12A3 SCN7A SCN5A SCN4A
7 muscle contraction GO:0006936 9.85 SCN7A SCN4A RYR1 KCNJ12 CLCN1 CACNA1S
8 sodium ion transmembrane transport GO:0035725 9.84 SLC12A3 SCN7A SCN5A SCN4A
9 protein homotetramerization GO:0051289 9.79 RYR1 KCNJ2 KCNJ12
10 potassium ion import across plasma membrane GO:1990573 9.78 SLC12A3 KCNJ2 KCNJ18 KCNJ12
11 calcium ion import GO:0070509 9.76 CACNA1S CACNA1F CACNA1D CACNA1C
12 cardiac muscle cell action potential involved in contraction GO:0086002 9.73 SCN5A KCNJ2 CACNA1D CACNA1C
13 regulation of ion transmembrane transport GO:0034765 9.73 SCN7A SCN5A SCN4A KCNJ2 KCNJ18 KCNJ12
14 neuronal action potential GO:0019228 9.72 SCN7A SCN5A SCN4A
15 regulation of heart rate by cardiac conduction GO:0086091 9.72 SCN5A KCNJ2 KCNE3 CACNA1D CACNA1C
16 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.71 SCN5A KCNJ2 CACNA1D CACNA1C
17 membrane depolarization during action potential GO:0086010 9.7 SCN7A SCN5A SCN4A
18 cardiac conduction GO:0061337 9.7 SCN5A KCNJ2 KCNJ12 CACNA1S CACNA1F CACNA1D
19 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.65 SCN5A KCNE3
20 ventricular cardiac muscle cell action potential GO:0086005 9.65 SCN5A KCNE3
21 sodium ion homeostasis GO:0055078 9.64 SLC12A3 SCN7A
22 regulation of cardiac muscle cell contraction GO:0086004 9.64 SCN5A KCNJ2
23 cellular response to caffeine GO:0071313 9.63 RYR1 CACNA1S
24 membrane repolarization during action potential GO:0086011 9.63 KCNJ2 KCNE3
25 positive regulation of adenylate cyclase activity GO:0045762 9.62 CACNA1D CACNA1C
26 positive regulation of voltage-gated calcium channel activity GO:1901387 9.62 STAC3 KCNE3
27 regulation of atrial cardiac muscle cell membrane repolarization GO:0060372 9.61 SCN5A CACNA1D
28 membrane depolarization during SA node cell action potential GO:0086046 9.6 SCN5A CACNA1D
29 membrane depolarization during AV node cell action potential GO:0086045 9.59 SCN5A CACNA1C
30 membrane depolarization during atrial cardiac muscle cell action potential GO:0098912 9.56 SCN5A CACNA1C
31 ion transport GO:0006811 9.47 SLC12A3 SCN7A SCN5A SCN4A RYR1 KCNJ2

Molecular functions related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 calmodulin binding GO:0005516 9.8 SCN5A RYR1 CACNA1S CACNA1C
2 calcium channel activity GO:0005262 9.72 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
3 cation channel activity GO:0005261 9.65 SCN7A SCN5A SCN4A
4 voltage-gated calcium channel activity GO:0005245 9.65 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
5 sodium channel activity GO:0005272 9.61 SCN7A SCN5A SCN4A
6 voltage-gated sodium channel activity GO:0005248 9.58 SCN7A SCN5A SCN4A
7 ion channel activity GO:0005216 9.56 SCN7A SCN5A SCN4A RYR1 CACNA1S CACNA1F
8 inward rectifier potassium channel activity GO:0005242 9.54 KCNJ2 KCNJ18 KCNJ12
9 ankyrin binding GO:0030506 9.52 SCN5A CACNA1D
10 alpha-actinin binding GO:0051393 9.51 CACNA1D CACNA1C
11 voltage-gated calcium channel activity involved in cardiac muscle cell action potential GO:0086007 9.46 CACNA1D CACNA1C
12 high voltage-gated calcium channel activity GO:0008331 9.46 CACNA1S CACNA1F CACNA1D CACNA1C
13 voltage-gated ion channel activity GO:0005244 9.4 SCN7A SCN5A SCN4A KCNJ2 KCNJ18 KCNJ12

Sources for Hypokalemic Periodic Paralysis, Type 1

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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