HOKPP1
MCID: HYP370
MIFTS: 64

Hypokalemic Periodic Paralysis, Type 1 (HOKPP1)

Categories: Blood diseases, Genetic diseases, Metabolic 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 56 13
Hypokalemic Periodic Paralysis 56 12 74 24 52 25 58 36 29 54 6 43 15 71
Hokpp 56 24 52 25 73
Hypopp 24 52 25 73
Westphall Disease 25 58 73
Familial Hypokalemic Periodic Paralysis 12 25
Hypokalemic Periodic Paralysis Type 1 74 71
Hypokalemic Periodic Paralysis 1 29 6
Familial Periodic Paralysis 12 71
Hokpp1 56 73
Paralysis, Hypokalemic, Periodic, Type 1 39
Hypokalemic Familial Periodic Paralysis 12
Primary Hypokalemic Periodic Paralysis 25
Hypokalemic Periodic Paralysis; Hokpp 56
Periodic Paralysis Hypokalemic 1 73
Paralysis, Hypokalemic, Periodic 39
Periodic Hypokalemic Paralysis 12
Periodic Paralysis I 12
Westphal Disease 12
Hypokpp 25

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:

56
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:

24
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 56 170400
KEGG 36 H00746
MeSH 43 D020514
NCIt 49 C84775
SNOMED-CT 67 82732003
ICD10 32 G72.3
MESH via Orphanet 44 D020514
ICD10 via Orphanet 33 G72.3
UMLS via Orphanet 72 C0238357 C0238358
Orphanet 58 ORPHA681
UMLS 71 C0030443 C0238358 C3714580

Summaries for Hypokalemic Periodic Paralysis, Type 1

Genetics Home Reference : 25 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 hypokalemic periodic paralysis, type 2 and thyrotoxic periodic paralysis, 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

NIH Rare Diseases : 52 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 : 56 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)

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 : 73 Periodic paralysis hypokalemic 1: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.

Wikipedia : 74 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 192)
# Related Disease Score Top Affiliating Genes
1 hypokalemic periodic paralysis, type 2 35.0 SCN7A SCN4A QDPR
2 thyrotoxic periodic paralysis 34.2 KCNJ2 KCNJ18 CACNA1S
3 periodic paralyses 33.2 SCN4A KCNJ2 KCNE3 CACNA1S
4 thyrotoxic periodic paralysis 1 33.0 KCNJ18 CACNA1S
5 graves disease 1 31.8 SCN4A KCNJ18 INS CACNA1S
6 myotonia 31.8 SCN4A CLCN1
7 hyperthyroidism 31.5 KCNJ18 INS CACNA1S
8 hypokalemia 31.5 SLC12A3 SCN4A KCNJ18 INS CACNA1S CACNA1D
9 cardiac arrhythmia 31.0 SCN5A KCNJ2 CACNA1C
10 myotonia congenita 30.9 SCN4A KCNJ2 CLCN1 CACNA1S
11 normokalemic periodic paralysis 30.8 SCN7A SCN4A
12 malignant hyperthermia susceptibility 30.8 SCN4A RYR1 CACNA1S
13 periodic paralysis 30.7 SCN7A SCN4A RYR1 KCNJ2 KCNJ18 KCNE3
14 malignant hyperthermia 30.6 SCN7A SCN5A SCN4A RYR1 QDPR CACNA1S
15 neuromuscular disease 30.4 SCN5A SCN4A RYR1 CLCN1 CACNA1S
16 andersen cardiodysrhythmic periodic paralysis 30.3 SCN5A SCN4A KCNJ2 KCNJ18 KCNJ12 KCNE3
17 hyperkalemic periodic paralysis 30.3 SCN5A SCN4A SCN2A NAV1 KCNJ2 KCNJ18
18 ventricular fibrillation, paroxysmal familial, 1 30.3 SCN5A CACNA1C
19 familial periodic paralysis 30.2 TMEM266 SLC12A3 SCN5A SCN4A SCN2A RYR1
20 isolated elevated serum creatine phosphokinase levels 30.2 SCN5A SCN4A RYR1 KCNJ12 CLCN1 CACNA1C
21 paramyotonia congenita of von eulenburg 29.9 SCN5A SCN4A SCN2A NAV1 KCNJ2 KCNJ18
22 thyrotoxic periodic paralysis 2 12.3
23 familial periodic paralyses 11.7
24 wolff-parkinson-white syndrome 11.7
25 graves' disease 10.7
26 renal tubular acidosis 10.6
27 myopathy 10.6
28 distal renal tubular acidosis 10.5
29 hypothyroidism 10.5
30 brugada syndrome 6 10.5 SCN5A KCNE3
31 myopathy, congenital, bailey-bloch 10.5 RYR1 CACNA1S CACNA1C
32 central core myopathy 10.5 RYR1 QDPR CACNA1S
33 long qt syndrome 15 10.5 KCNJ2 CACNA1C
34 quadriplegia 10.4
35 familial long qt syndrome 10.4 SCN5A KCNJ2 CACNA1C
36 uvulitis 10.4 KCNJ18 INS
37 myotonic disease 10.4 SCN4A RYR1 CLCN1
38 long qt syndrome 14 10.4 SCN5A KCNJ2 CACNA1C
39 long qt syndrome 6 10.4 SCN5A KCNJ2 CACNA1C
40 central core disease of muscle 10.4 RYR1 CACNA1S
41 long qt syndrome 9 10.4 SCN5A KCNJ2 CACNA1C
42 right bundle branch block 10.4 SCN5A KCNE3 CACNA1C
43 spinocerebellar ataxia 6 10.4 CACNA1S CACNA1F CACNA1C
44 first-degree atrioventricular block 10.4 SCN5A KCNJ2
45 neuromuscular junction disease 10.4 SCN5A SCN4A CACNA1C
46 myasthenia gravis 10.4
47 sjogren syndrome 10.4
48 metabolic acidosis 10.4
49 long qt syndrome 13 10.4 SCN5A KCNJ2
50 familial hemiplegic migraine 10.4 SCN5A CACNA1S CACNA1C

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 19)
# 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 increased intramyocellular lipid droplets 58 31 hallmark (90%) Very frequent (99-80%) HP:0012240
6 mildly elevated creatine kinase 31 hallmark (90%) HP:0008180
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 mildly elevated creatine phosphokinase 58 Very frequent (99-80%)
17 paralysis 58 Very frequent (99-80%)
18 abnormality of muscle fibers 58 Very frequent (99-80%)
19 impaired myocardial contractility 58 Excluded (0%)

Symptoms via clinical synopsis from OMIM:

56
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

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:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.1 CACNA1C CACNA1D CACNA1F CACNA1S CLCN1 INS
2 cardiovascular system MP:0005385 10 CACNA1C CACNA1D CACNA1S INS KCNE3 KCNJ11
3 homeostasis/metabolism MP:0005376 9.97 CACNA1C CACNA1D CACNA1S CLCN1 INS KCNE3
4 muscle MP:0005369 9.61 CACNA1C CACNA1S CLCN1 INS KCNJ11 KCNJ2
5 respiratory system MP:0005388 9.17 CACNA1S KCNE3 KCNJ2 RYR1 SCN2A SCN4A

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 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 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, Testes, Pituitary, Brain

Publications for Hypokalemic Periodic Paralysis, Type 1

Articles related to Hypokalemic Periodic Paralysis, Type 1:

(show top 50) (show all 653)
# Title Authors PMID Year
1
Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. 24 56 6 61 54
10944223 2000
2
Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene. 6 24 56
18835861 2008
3
Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK. 56 6 61 54
11591859 2001
4
Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. 6 56 61
8004673 1994
5
Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia. 61 24 6
21490317 2011
6
Correlating phenotype and genotype in the periodic paralyses. 56 24 61
15534250 2004
7
Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis. 56 6
7897626 1995
8
Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family. 61 54 6
19779499 2009
9
Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. 56 61 54
19118277 2009
10
Gating pore current in an inherited ion channelopathy. 24 56
17330043 2007
11
Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis. 54 6 61
16890191 2006
12
Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. 61 6 54
14557559 2003
13
Enhanced inactivation and pH sensitivity of Na(+) channel mutations causing hypokalaemic periodic paralysis type II. 24 6
11912116 2002
14
Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. 24 56
11353725 2001
15
A novel sodium channel mutation in a family with hypokalemic periodic paralysis. 6 61 54
10599760 1999
16
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. 61 54 6
7847370 1995
17
Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge. 56 61
16608889 2006
18
Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family. 54 24 61
15726306 2005
19
Thyrotoxic periodic paralysis associated with a mutation in the sodium channel gene SCN4A. 54 24 61
15645704 2004
20
SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide. 61 6
15557532 2004
21
Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis. 54 61 24
15072700 2004
22
Hypokalemic Periodic Paralysis 61 6
20301512 2002
23
Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis. 61 6
11558801 2001
24
Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis. 6 61
10074484 1999
25
Genetic heterogeneity in hypokalemic periodic paralysis (hypoPP). 61 56
7959693 1994
26
A calcium channel mutation causing hypokalemic periodic paralysis. 6 61
7987325 1994
27
Diagnosis of familial hypokalemic periodic paralysis: role of the potassium exercise test. 56 61
1436528 1992
28
Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci. 56 61
1330884 1992
29
Different gene loci for hyperkalemic and hypokalemic periodic paralysis. 61 56
1822800 1991
30
Hypokalemic periodic paralysis due to the Sjögren syndrome in Chinese patients. 56 61
2916810 1989
31
Familial hypokalemic periodic paralysis. 50-year follow-up of a large family. 61 56
3855357 1985
32
Hypokalemic periodic paralysis in Sjögren's syndrome. 56 61
7305577 1981
33
Erythrocyte membrane studies in familial hypokalemic periodic paralysis. 61 56
150837 1978
34
Familial hypokalemic periodic paralysis in blacks. 61 56
1147439 1975
35
Familial hypokalemic periodic paralysis. 56 61
4834972 1974
36
An atypical CaV1.1 mutation reveals a common mechanism for hypokalemic periodic paralysis. 61 24
29138267 2017
37
Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy. 61 24
28012042 2017
38
Prevalence study of genetically defined skeletal muscle channelopathies in England. 61 24
23516313 2013
39
Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis. 61 24
23427324 2013
40
Genotype and phenotype analysis of patients with sporadic periodic paralysis. 24 61
21841462 2012
41
Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype. 61 24
22094484 2011
42
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. 6
20298421 2010
43
Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. 61 24
20074522 2010
44
K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks. 24 61
19225109 2009
45
Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis. 61 24
19052238 2008
46
Gating pore currents in DIIS4 mutations of NaV1.4 associated with periodic paralysis: saturation of ion flux and implications for disease pathogenesis. 61 24
18824591 2008
47
Practical aspects in the management of hypokalemic periodic paralysis. 61 24
18426576 2008
48
Treatment for periodic paralysis. 61 24
18254068 2008
49
A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. 61 24
17591984 2007
50
Myopathy as the first symptom of hypokalemic periodic paralysis--case report of a girl from a Polish family with CACNA1S (R1239G) mutation. 24 61
18229654 2007

Variations for Hypokalemic Periodic Paralysis, Type 1

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

6 (show top 50) (show all 545) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CACNA1S NM_000069.3(CACNA1S):c.1503C>A (p.Cys501Ter)SNV Pathogenic 473964 rs762294904 1:201047123-201047123 1:201077995-201077995
2 CACNA1S NM_000069.3(CACNA1S):c.564del (p.Ile189fs)deletion Pathogenic 541039 rs1553252746 1:201060898-201060898 1:201091770-201091770
3 CACNA1S NM_000069.3(CACNA1S):c.1796del (p.Asn599fs)deletion Pathogenic 567517 rs1558071742 1:201046079-201046079 1:201076951-201076951
4 CACNA1S NM_000069.3(CACNA1S):c.4871_4874del (p.Asn1624fs)deletion Pathogenic 665842 1:201012583-201012586 1:201043455-201043458
5 CACNA1S NM_000069.3(CACNA1S):c.4025C>A (p.Ser1342Ter)SNV Pathogenic 641633 1:201020200-201020200 1:201051072-201051072
6 CACNA1S NM_000069.3(CACNA1S):c.2970G>A (p.Trp990Ter)SNV Pathogenic 643605 1:201031155-201031155 1:201062027-201062027
7 CACNA1S NM_000069.3(CACNA1S):c.2812del (p.Leu938fs)deletion Pathogenic 656431 1:201035007-201035007 1:201065879-201065879
8 CACNA1S NM_000069.3(CACNA1S):c.1847G>A (p.Trp616Ter)SNV Pathogenic 665684 1:201044724-201044724 1:201075596-201075596
9 CACNA1S NM_000069.3(CACNA1S):c.897C>G (p.Tyr299Ter)SNV Pathogenic 649853 1:201058389-201058389 1:201089261-201089261
10 CACNA1S NM_000069.3(CACNA1S):c.732del (p.Cys245fs)deletion Pathogenic 646905 1:201058554-201058554 1:201089426-201089426
11 CACNA1S NM_000069.3(CACNA1S):c.4947del (p.Asp1650fs)deletion Pathogenic 848766 1:201012510-201012510 1:201043382-201043382
12 CACNA1S NM_000069.3(CACNA1S):c.3025_3026del (p.Thr1009fs)deletion Pathogenic 862482 1:201031099-201031100 1:201061971-201061972
13 CACNA1S NM_000069.3(CACNA1S):c.19C>T (p.Gln7Ter)SNV Pathogenic 854887 1:201081449-201081449 1:201112321-201112321
14 CACNA1S NM_000069.3(CACNA1S):c.3773G>A (p.Trp1258Ter)SNV Pathogenic 856306 1:201022609-201022609 1:201053481-201053481
15 SCN4A NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met)SNV Pathogenic 5896 rs80338957 17:62034787-62034787 17:63957427-63957427
16 SCN4A NM_000334.4(SCN4A):c.4774A>G (p.Met1592Val)SNV Pathogenic 5897 rs80338962 17:62018868-62018868 17:63941508-63941508
17 SCN4A NM_000334.4(SCN4A):c.3938C>T (p.Thr1313Met)SNV Pathogenic 5904 rs121908547 17:62021185-62021185 17:63943825-63943825
18 SCN4A NM_000334.4(SCN4A):c.1333G>A (p.Val445Met)SNV Pathogenic 5910 rs121908552 17:62041947-62041947 17:63964587-63964587
19 SCN4A NM_000334.4(SCN4A):c.2006G>A (p.Arg669His)SNV Pathogenic 5911 rs80338784 17:62036638-62036638 17:63959278-63959278
20 SCN4A NM_000334.4(SCN4A):c.2015G>A (p.Arg672His)SNV Pathogenic 5912 rs80338788 17:62036629-62036629 17:63959269-63959269
21 SCN4A NM_000334.4(SCN4A):c.2014C>G (p.Arg672Gly)SNV Pathogenic 5913 rs80338785 17:62036630-62036630 17:63959270-63959270
22 SCN4A NM_000334.4(SCN4A):c.2014C>A (p.Arg672Ser)SNV Pathogenic 5916 rs80338785 17:62036630-62036630 17:63959270-63959270
23 CACNA1S NM_000069.3(CACNA1S):c.3715C>G (p.Arg1239Gly)SNV Pathogenic 17624 rs28930069 1:201022667-201022667 1:201053539-201053539
24 CACNA1S NM_000069.3(CACNA1S):c.1583G>A (p.Arg528His)SNV Pathogenic 17625 rs80338777 1:201047043-201047043 1:201077915-201077915
25 CACNA1S NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His)SNV Pathogenic 17623 rs28930068 1:201022666-201022666 1:201053538-201053538
26 CACNA1S NM_000069.3(CACNA1S):c.2627T>A (p.Val876Glu)SNV Pathogenic 17631 rs267606698 1:201036045-201036045 1:201066917-201066917
27 CACNA1S NM_000069.3(CACNA1S):c.1582C>G (p.Arg528Gly)SNV Pathogenic 21034 rs80338778 1:201047044-201047044 1:201077916-201077916
28 CACNA1S NM_000069.3(CACNA1S):c.2748C>G (p.His916Gln)SNV Pathogenic 143198 rs2297902 1:201035071-201035071 1:201065943-201065943
29 SCN4A NM_000334.4(SCN4A):c.2014C>T (p.Arg672Cys)SNV Pathogenic 21151 rs80338785 17:62036630-62036630 17:63959270-63959270
30 SCN4A NM_000334.4(SCN4A):c.3395G>A (p.Arg1132Gln)SNV Pathogenic 21155 rs80338789 17:62024451-62024451 17:63947091-63947091
31 CACNA1S NM_000069.3(CACNA1S):c.3526-2A>GSNV Pathogenic 209137 rs797045031 1:201027621-201027621 1:201058493-201058493
32 SCN4A NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp)SNV Pathogenic/Likely pathogenic 143199 rs527236148 17:62048561-62048561 17:63971201-63971201
33 CACNA1S NM_000069.3(CACNA1S):c.502C>T (p.Arg168Ter)SNV Pathogenic/Likely pathogenic 504167 rs201998231 1:201061139-201061139 1:201092011-201092011
34 SCN4A NM_000334.4(SCN4A):c.4776G>A (p.Met1592Ile)SNV Likely pathogenic 427072 rs886041805 17:62018866-62018866 17:63941506-63941506
35 CACNA1S NM_000069.3(CACNA1S):c.4113+1G>CSNV Likely pathogenic 567328 rs1558056376 1:201020111-201020111 1:201050983-201050983
36 CACNA1S NM_000069.3(CACNA1S):c.1734G>A (p.Met578Ile)SNV Likely pathogenic 801605 1:201046141-201046141 1:201077013-201077013
37 CACNA1S NM_000069.3(CACNA1S):c.1582C>T (p.Arg528Cys)SNV Likely pathogenic 849085 1:201047044-201047044 1:201077916-201077916
38 CACNA1S NM_000069.3(CACNA1S):c.4798-2A>GSNV Likely pathogenic 639552 1:201012661-201012661 1:201043533-201043533
39 CACNA1S NM_000069.3(CACNA1S):c.3525+1G>ASNV Likely pathogenic 653789 1:201028316-201028316 1:201059188-201059188
40 CACNA1S NM_000069.3(CACNA1S):c.2854-2A>CSNV Likely pathogenic 653974 1:201031644-201031644 1:201062516-201062516
41 CACNA1S NM_000069.3(CACNA1S):c.520C>T (p.Arg174Trp)SNV drug response 575733 rs772226819 1:201061121-201061121 1:201091993-201091993
42 CACNA1S NM_000069.3(CACNA1S):c.1592G>A (p.Arg531His)SNV Conflicting interpretations of pathogenicity 643922 1:201047034-201047034 1:201077906-201077906
43 CACNA1S NM_000069.3(CACNA1S):c.2490+5C>TSNV Conflicting interpretations of pathogenicity 646258 1:201038595-201038595 1:201069467-201069467
44 CACNA1S NM_000069.3(CACNA1S):c.699C>T (p.Ile233=)SNV Conflicting interpretations of pathogenicity 699947 1:201058587-201058587 1:201089459-201089459
45 CACNA1S NM_000069.3(CACNA1S):c.744G>C (p.Thr248=)SNV Conflicting interpretations of pathogenicity 754960 1:201058542-201058542 1:201089414-201089414
46 CACNA1S NM_000069.3(CACNA1S):c.1591C>T (p.Arg531Cys)SNV Conflicting interpretations of pathogenicity 806320 1:201047035-201047035 1:201077907-201077907
47 CACNA1S NM_000069.3(CACNA1S):c.1385G>A (p.Arg462His)SNV Conflicting interpretations of pathogenicity 585658 rs146696298 1:201052298-201052298 1:201083170-201083170
48 SCN4A NM_000334.4(SCN4A):c.2704G>A (p.Gly902Ser)SNV Conflicting interpretations of pathogenicity 543804 rs200517944 17:62028933-62028933 17:63951573-63951573
49 CACNA1S NM_000069.3(CACNA1S):c.4718C>T (p.Thr1573Met)SNV Conflicting interpretations of pathogenicity 541073 rs183195890 1:201013535-201013535 1:201044407-201044407
50 SCN4A NM_000334.4(SCN4A):c.1018G>A (p.Ala340Thr)SNV Conflicting interpretations of pathogenicity 429845 rs147936148 17:62045401-62045401 17:63968041-63968041

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

73
# 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 45)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.51 SCN7A SCN5A SCN4A SCN2A RYR1 CLCN1
2
Show member pathways
13.46 SCN7A SCN5A SCN4A SCN2A INS CACNA1S
3
Show member pathways
12.98 SCN7A SCN5A SCN4A SCN2A CACNA1S CACNA1F
4
Show member pathways
12.88 KCNJ11 INS CACNA1S CACNA1F CACNA1D CACNA1C
5
Show member pathways
12.77 RYR1 INS CACNA1S CACNA1D CACNA1C
6 12.73 INS CACNA1S CACNA1F CACNA1D CACNA1C
7
Show member pathways
12.64 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
8
Show member pathways
12.64 SLC12A3 SCN7A SCN5A SCN4A SCN2A CLCN1
9
Show member pathways
12.64 RYR1 KCNJ2 KCNJ18 KCNJ12 CACNA1S CACNA1F
10
Show member pathways
12.58 CACNA1S CACNA1F CACNA1D CACNA1C
11 12.53 SCN7A SCN5A SCN4A SCN2A
12
Show member pathways
12.51 CACNA1S CACNA1F CACNA1D CACNA1C
13
Show member pathways
12.5 SCN7A SCN5A INS CACNA1S CACNA1F CACNA1D
14
Show member pathways
12.48 RYR1 CACNA1S CACNA1D CACNA1C
15
Show member pathways
12.47 RYR1 CACNA1S CACNA1D CACNA1C
16
Show member pathways
12.38 RYR1 KCNJ2 KCNJ18 KCNJ12 CACNA1S CACNA1F
17
Show member pathways
12.33 KCNJ11 INS CACNA1D CACNA1C
18 12.29 CACNA1S CACNA1F CACNA1D CACNA1C
19
Show member pathways
12.28 CACNA1S CACNA1F CACNA1D CACNA1C
20
Show member pathways
12.27 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
21
Show member pathways
12.22 CACNA1S CACNA1F CACNA1D CACNA1C
22 12.22 KCNJ2 KCNJ12 KCNJ11 KCNE3 CACNA1S CACNA1F
23
Show member pathways
12.16 SCN7A SCN5A SCN4A SCN2A RYR1 KCNJ2
24
Show member pathways
12.12 CACNA1S CACNA1F CACNA1D CACNA1C
25 12.11 CACNA1S CACNA1F CACNA1D CACNA1C
26 12.09 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
27
Show member pathways
12.03 CACNA1S CACNA1F CACNA1D CACNA1C
28
Show member pathways
12.01 SCN7A SCN5A SCN4A SCN2A
29
Show member pathways
11.99 INS CLCN1 CACNA1S CACNA1D CACNA1C
30 11.97 CACNA1S CACNA1F CACNA1D CACNA1C
31
Show member pathways
11.92 KCNJ2 KCNJ12 KCNJ11
32
Show member pathways
11.88 KCNJ11 INS CACNA1D CACNA1C
33 11.82 CACNA1S CACNA1F CACNA1D CACNA1C
34 11.68 CACNA1S CACNA1F CACNA1D CACNA1C
35 11.67 KCNJ2 CACNA1S CACNA1F CACNA1D CACNA1C
36 11.61 CACNA1S CACNA1F CACNA1D CACNA1C
37 11.61 KCNJ11 CACNA1S CACNA1F CACNA1D CACNA1C
38 11.52 RYR1 CACNA1S CACNA1D CACNA1C
39
Show member pathways
11.48 SCN7A SCN5A SCN4A SCN2A KCNE3 CACNA1S
40 11.38 SCN5A KCNJ2 KCNJ11 KCNE3 CACNA1D CACNA1C
41 11.37 CACNA1S CACNA1D CACNA1C
42 11.26 SCN7A SCN5A SCN4A SCN2A
43
Show member pathways
11.09 CACNA1F CACNA1D CACNA1C
44 10.75 CACNA1D CACNA1C
45 10.75 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 10.41 TMEM266 SLC12A3 SCN7A SCN5A SCN4A SCN2A
2 integral component of membrane GO:0016021 10.19 TMEM266 SLC12A3 SCN7A SCN5A SCN4A SCN2A
3 integral component of plasma membrane GO:0005887 10.11 TMEM266 SLC12A3 SCN4A SCN2A RYR1 KCNJ2
4 plasma membrane GO:0005886 9.89 TMEM266 SLC12A3 SCN7A SCN5A SCN4A SCN2A
5 perikaryon GO:0043204 9.81 TMEM266 KCNE3 CACNA1F CACNA1C
6 Z disc GO:0030018 9.8 SCN5A RYR1 CACNA1D CACNA1C
7 sarcolemma GO:0042383 9.77 SCN5A RYR1 KCNJ11 CLCN1 CACNA1C
8 intercalated disc GO:0014704 9.71 SCN5A SCN2A KCNJ2 KCNJ11
9 voltage-gated calcium channel complex GO:0005891 9.62 CACNA1S CACNA1F CACNA1D CACNA1C
10 L-type voltage-gated calcium channel complex GO:1990454 9.61 CACNA1S CACNA1D CACNA1C
11 intrinsic component of membrane GO:0031224 9.52 KCNJ2 KCNJ12
12 voltage-gated sodium channel complex GO:0001518 9.46 SCN7A SCN5A SCN4A SCN2A
13 T-tubule GO:0030315 9.17 SCN5A SCN2A RYR1 KCNJ2 KCNJ11 CACNA1S

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 ion transmembrane transport GO:0034220 10.04 SCN7A SCN5A SCN2A RYR1 KCNJ11 CLCN1
2 calcium ion transport GO:0006816 9.97 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
3 potassium ion transport GO:0006813 9.97 KCNJ2 KCNJ18 KCNJ12 KCNJ11 KCNE3
4 transmembrane transport GO:0055085 9.97 TMEM266 SLC12A3 SCN7A SCN5A SCN4A SCN2A
5 calcium ion transmembrane transport GO:0070588 9.96 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
6 sodium ion transport GO:0006814 9.95 SLC12A3 SCN7A SCN5A SCN4A SCN2A
7 sodium ion transmembrane transport GO:0035725 9.92 SLC12A3 SCN7A SCN5A SCN4A SCN2A
8 muscle contraction GO:0006936 9.91 SCN7A SCN4A RYR1 KCNJ12 CLCN1 CACNA1S
9 neuronal action potential GO:0019228 9.84 SCN7A SCN5A SCN4A SCN2A
10 calcium ion import GO:0070509 9.81 CACNA1S CACNA1F CACNA1D CACNA1C
11 regulation of insulin secretion GO:0050796 9.8 KCNJ11 CACNA1D CACNA1C
12 cardiac conduction GO:0061337 9.8 SCN5A KCNJ2 KCNJ12 CACNA1S CACNA1F CACNA1D
13 regulation of ion transmembrane transport GO:0034765 9.8 SCN7A SCN5A SCN4A SCN2A KCNJ2 KCNJ18
14 protein homotetramerization GO:0051289 9.79 RYR1 KCNJ2 KCNJ12
15 membrane depolarization during action potential GO:0086010 9.78 SCN7A SCN5A SCN4A SCN2A
16 potassium ion import across plasma membrane GO:1990573 9.77 SLC12A3 KCNJ2 KCNJ18 KCNJ12 KCNJ11
17 cardiac muscle cell action potential involved in contraction GO:0086002 9.76 SCN5A KCNJ2 CACNA1D CACNA1C
18 regulation of heart rate by cardiac conduction GO:0086091 9.72 SCN5A KCNJ2 KCNE3 CACNA1D CACNA1C
19 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.71 SCN5A KCNJ2 CACNA1D CACNA1C
20 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.65 SCN5A KCNE3
21 ventricular cardiac muscle cell action potential GO:0086005 9.65 SCN5A KCNE3
22 sodium ion homeostasis GO:0055078 9.64 SLC12A3 SCN7A
23 regulation of cardiac muscle cell contraction GO:0086004 9.64 SCN5A KCNJ2
24 cellular response to caffeine GO:0071313 9.63 RYR1 CACNA1S
25 membrane repolarization during action potential GO:0086011 9.62 KCNJ2 KCNE3
26 positive regulation of adenylate cyclase activity GO:0045762 9.62 CACNA1D CACNA1C
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 9.58 SCN5A CACNA1C
31 ion transport GO:0006811 9.53 SLC12A3 SCN7A SCN5A SCN4A SCN2A RYR1

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 9.81 SCN5A RYR1 CACNA1S CACNA1C
2 calcium channel activity GO:0005262 9.8 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
3 cation channel activity GO:0005261 9.76 SCN7A SCN5A SCN4A SCN2A
4 sodium channel activity GO:0005272 9.73 SCN7A SCN5A SCN4A SCN2A
5 voltage-gated sodium channel activity GO:0005248 9.67 SCN7A SCN5A SCN4A SCN2A
6 ankyrin binding GO:0030506 9.65 SCN5A KCNJ11 CACNA1D
7 voltage-gated calcium channel activity GO:0005245 9.65 RYR1 CACNA1S CACNA1F CACNA1D CACNA1C
8 inward rectifier potassium channel activity GO:0005242 9.62 KCNJ2 KCNJ18 KCNJ12 KCNJ11
9 ion channel activity GO:0005216 9.61 SCN7A SCN5A SCN4A SCN2A RYR1 CACNA1S
10 alpha-actinin binding GO:0051393 9.52 CACNA1D CACNA1C
11 voltage-gated calcium channel activity involved in cardiac muscle cell action potential GO:0086007 9.49 CACNA1D CACNA1C
12 voltage-gated ion channel activity GO:0005244 9.47 SCN7A SCN5A SCN4A SCN2A KCNJ2 KCNJ18
13 high voltage-gated calcium channel activity GO:0008331 9.46 CACNA1S CACNA1F CACNA1D CACNA1C

Sources for Hypokalemic Periodic Paralysis, Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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