HOKPP2
MCID: HYP606
MIFTS: 37

Hypokalemic Periodic Paralysis, Type 2 (HOKPP2)

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

Aliases & Classifications for Hypokalemic Periodic Paralysis, Type 2

MalaCards integrated aliases for Hypokalemic Periodic Paralysis, Type 2:

Name: Hypokalemic Periodic Paralysis, Type 2 57 29 13 6 70
Hokpp2 57 72
Paralysis, Hypokalemic, Periodic, Type 2 39
Periodic Paralysis Hypokalemic 2 72

Characteristics:

OMIM®:

57 (Updated 20-May-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 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM® 57 613345
MeSH 44 D020514
MedGen 41 C2750061
UMLS 70 C2750061

Summaries for Hypokalemic Periodic Paralysis, Type 2

UniProtKB/Swiss-Prot : 72 Periodic paralysis hypokalemic 2: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.

MalaCards based summary : Hypokalemic Periodic Paralysis, Type 2, also known as hokpp2, is related to hyperkalemic periodic paralysis and myotonia, potassium-aggravated. An important gene associated with Hypokalemic Periodic Paralysis, Type 2 is SCN4A (Sodium Voltage-Gated Channel Alpha Subunit 4), and among its related pathways/superpathways are L1CAM interactions and Phase 0 - rapid depolarisation. Affiliated tissues include skeletal muscle, and related phenotypes are hypokalemia and myopathy

More information from OMIM: 613345

Related Diseases for Hypokalemic Periodic Paralysis, Type 2

Graphical network of the top 20 diseases related to Hypokalemic Periodic Paralysis, Type 2:



Diseases related to Hypokalemic Periodic Paralysis, Type 2

Symptoms & Phenotypes for Hypokalemic Periodic Paralysis, Type 2

Human phenotypes related to Hypokalemic Periodic Paralysis, Type 2:

31
# Description HPO Frequency HPO Source Accession
1 hypokalemia 31 HP:0002900
2 myopathy 31 HP:0003198
3 episodic flaccid weakness 31 HP:0003752
4 periodic paralysis 31 HP:0003768

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-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®:

613345 (Updated 20-May-2021)

Drugs & Therapeutics for Hypokalemic Periodic Paralysis, Type 2

Search Clinical Trials , NIH Clinical Center for Hypokalemic Periodic Paralysis, Type 2

Genetic Tests for Hypokalemic Periodic Paralysis, Type 2

Genetic tests related to Hypokalemic Periodic Paralysis, Type 2:

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

Anatomical Context for Hypokalemic Periodic Paralysis, Type 2

MalaCards organs/tissues related to Hypokalemic Periodic Paralysis, Type 2:

40
Skeletal Muscle

Publications for Hypokalemic Periodic Paralysis, Type 2

Articles related to Hypokalemic Periodic Paralysis, Type 2:

(show all 22)
# Title Authors PMID Year
1
Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. 61 57 6
10944223 2000
2
Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia. 6 57
21490317 2011
3
SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide. 6 57
15557532 2004
4
Enhanced inactivation and pH sensitivity of Na(+) channel mutations causing hypokalaemic periodic paralysis type II. 6 57
11912116 2002
5
Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK. 57 6
11591859 2001
6
Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis. 6 57
10851391 2000
7
A novel sodium channel mutation in a family with hypokalemic periodic paralysis. 6 57
10599760 1999
8
Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis. 6 61
16890191 2006
9
Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. 57
19118277 2009
10
Gating pore current in an inherited ion channelopathy. 57
17330043 2007
11
Correlating phenotype and genotype in the periodic paralyses. 57
15534250 2004
12
Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. 6
14557559 2003
13
Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis. 6
11558801 2001
14
Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. 57
11353725 2001
15
Skeletal muscle sodium current is reduced in hypokalemic periodic paralysis. 57
10954743 2000
16
Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters. 57
6325904 1984
17
The clinical and genetic heterogeneity analysis of five families with primary periodic paralysis. 61
33345742 2021
18
Association study in Mexican patients with thyrotoxic hypokalemic periodic paralysis. 61
32765863 2020
19
Myotonia congenita and periodic hypokalemia paralysis in a consanguineous marriage pedigree: Coexistence of a novel CLCN1 mutation and an SCN4A mutation. 61
32407401 2020
20
Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review. 61
30931713 2019
21
A Sodium Channel Myotonia Presenting with Intermittent Dysphagia as a Manifestation of a Rare SCN4A Variant. 61
28012096 2017
22
Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies. 61
12685554 2003

Variations for Hypokalemic Periodic Paralysis, Type 2

ClinVar genetic disease variations for Hypokalemic Periodic Paralysis, Type 2:

6 (show top 50) (show all 241)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3472C>T (p.Pro1158Ser) SNV Pathogenic 5917 rs121908555 GRCh37: 17:62022968-62022968
GRCh38: 17:63945608-63945608
2 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3395G>A (p.Arg1132Gln) SNV Pathogenic 21155 rs80338789 GRCh37: 17:62024451-62024451
GRCh38: 17:63947091-63947091
3 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3938C>T (p.Thr1313Met) SNV Pathogenic 5904 rs121908547 GRCh37: 17:62021185-62021185
GRCh38: 17:63943825-63943825
4 SCN4A NM_000334.4(SCN4A):c.1333G>A (p.Val445Met) SNV Pathogenic 5910 rs121908552 GRCh37: 17:62041947-62041947
GRCh38: 17:63964587-63964587
5 SCN4A NM_000334.4(SCN4A):c.2006G>A (p.Arg669His) SNV Pathogenic 5911 rs80338784 GRCh37: 17:62036638-62036638
GRCh38: 17:63959278-63959278
6 SCN4A NM_000334.4(SCN4A):c.2015G>A (p.Arg672His) SNV Pathogenic 5912 rs80338788 GRCh37: 17:62036629-62036629
GRCh38: 17:63959269-63959269
7 SCN4A NM_000334.4(SCN4A):c.2014C>G (p.Arg672Gly) SNV Pathogenic 5913 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
8 SCN4A NM_000334.4(SCN4A):c.2014C>A (p.Arg672Ser) SNV Pathogenic 5916 rs80338785 GRCh37: 17:62036630-62036630
GRCh38: 17:63959270-63959270
9 SCN4A NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp) SNV Pathogenic 143199 rs527236148 GRCh37: 17:62048561-62048561
GRCh38: 17:63971201-63971201
10 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3404G>A (p.Arg1135His) SNV Pathogenic 143201 rs527236150 GRCh37: 17:62024442-62024442
GRCh38: 17:63947082-63947082
11 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4774A>G (p.Met1592Val) SNV Pathogenic 5897 rs80338962 GRCh37: 17:62018868-62018868
GRCh38: 17:63941508-63941508
12 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met) SNV Pathogenic 5896 rs80338957 GRCh37: 17:62034787-62034787
GRCh38: 17:63957427-63957427
13 SCN4A NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp) SNV Likely pathogenic 143199 rs527236148 GRCh37: 17:62048561-62048561
GRCh38: 17:63971201-63971201
14 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4776G>A (p.Met1592Ile) SNV Likely pathogenic 427072 rs886041805 GRCh37: 17:62018866-62018866
GRCh38: 17:63941506-63941506
15 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3403C>A (p.Arg1135Ser) SNV Likely pathogenic 870587 GRCh37: 17:62024443-62024443
GRCh38: 17:63947083-63947083
16 SCN4A NM_000334.4(SCN4A):c.82A>C (p.Ile28Leu) SNV Uncertain significance 324554 rs886053250 GRCh37: 17:62050120-62050120
GRCh38: 17:63972760-63972760
17 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*1172G>A SNV Uncertain significance 324487 rs540304010 GRCh37: 17:62016959-62016959
GRCh38: 17:63939599-63939599
18 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*2211C>T SNV Uncertain significance 324463 rs886053237 GRCh37: 17:62015920-62015920
GRCh38: 17:63938560-63938560
19 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*1887A>G SNV Uncertain significance 324470 rs749866237 GRCh37: 17:62016244-62016244
GRCh38: 17:63938884-63938884
20 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2576G>A (p.Gly859Glu) SNV Uncertain significance 324533 rs886053248 GRCh37: 17:62029061-62029061
GRCh38: 17:63951701-63951701
21 GH-LCR , SCN4A NM_000334.4(SCN4A):c.5457C>T (p.Pro1819=) SNV Uncertain significance 324505 rs761023866 GRCh37: 17:62018185-62018185
GRCh38: 17:63940825-63940825
22 SCN4A NM_000334.4(SCN4A):c.858G>A (p.Pro286=) SNV Uncertain significance 324549 rs560230431 GRCh37: 17:62045561-62045561
GRCh38: 17:63968201-63968201
23 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*1875A>G SNV Uncertain significance 324471 rs886053239 GRCh37: 17:62016256-62016256
GRCh38: 17:63938896-63938896
24 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*873G>C SNV Uncertain significance 324492 rs540759411 GRCh37: 17:62017258-62017258
GRCh38: 17:63939898-63939898
25 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2626G>A (p.Glu876Lys) SNV Uncertain significance 324530 rs886053247 GRCh37: 17:62029011-62029011
GRCh38: 17:63951651-63951651
26 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4863C>T (p.Tyr1621=) SNV Uncertain significance 324513 rs769625349 GRCh37: 17:62018779-62018779
GRCh38: 17:63941419-63941419
27 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4891G>A (p.Ala1631Thr) SNV Uncertain significance 324511 rs201115695 GRCh37: 17:62018751-62018751
GRCh38: 17:63941391-63941391
28 SCN4A NM_000334.4(SCN4A):c.553G>A (p.Asp185Asn) SNV Uncertain significance 197134 rs778661227 GRCh37: 17:62049140-62049140
GRCh38: 17:63971780-63971780
29 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*1890C>A SNV Uncertain significance 324469 rs886053238 GRCh37: 17:62016241-62016241
GRCh38: 17:63938881-63938881
30 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3772G>A (p.Glu1258Lys) SNV Uncertain significance 324521 rs886053246 GRCh37: 17:62022369-62022369
GRCh38: 17:63945009-63945009
31 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*1253G>A SNV Uncertain significance 324484 rs886053240 GRCh37: 17:62016878-62016878
GRCh38: 17:63939518-63939518
32 SCN4A NM_000334.4(SCN4A):c.1356G>C (p.Glu452Asp) SNV Uncertain significance 324543 rs749394640 GRCh37: 17:62041924-62041924
GRCh38: 17:63964564-63964564
33 GH-LCR , SCN4A NM_000334.4(SCN4A):c.*394A>C SNV Uncertain significance 324497 rs886053244 GRCh37: 17:62017737-62017737
GRCh38: 17:63940377-63940377
34 GH-LCR , SCN4A NM_000334.4(SCN4A):c.5482C>T (p.Arg1828Cys) SNV Uncertain significance 577832 rs758511540 GRCh37: 17:62018160-62018160
GRCh38: 17:63940800-63940800
35 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4609G>A (p.Gly1537Ser) SNV Uncertain significance 222028 rs571210585 GRCh37: 17:62019033-62019033
GRCh38: 17:63941673-63941673
36 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4429A>G (p.Met1477Val) SNV Uncertain significance 543806 rs1465376529 GRCh37: 17:62019213-62019213
GRCh38: 17:63941853-63941853
37 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4222C>T (p.Arg1408Cys) SNV Uncertain significance 568015 rs118047588 GRCh37: 17:62020252-62020252
GRCh38: 17:63942892-63942892
38 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3004T>C (p.Trp1002Arg) SNV Uncertain significance 579545 rs544082594 GRCh37: 17:62026111-62026111
GRCh38: 17:63948751-63948751
39 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2704G>A (p.Gly902Ser) SNV Uncertain significance 543804 rs200517944 GRCh37: 17:62028933-62028933
GRCh38: 17:63951573-63951573
40 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2468A>C (p.Gln823Pro) SNV Uncertain significance 582148 rs753182664 GRCh37: 17:62029169-62029169
GRCh38: 17:63951809-63951809
41 SCN4A NM_000334.4(SCN4A):c.1139G>A (p.Arg380Gln) SNV Uncertain significance 570912 rs374446143 GRCh37: 17:62043565-62043565
GRCh38: 17:63966205-63966205
42 SCN4A NM_000334.4(SCN4A):c.1018G>A (p.Ala340Thr) SNV Uncertain significance 429845 rs147936148 GRCh37: 17:62045401-62045401
GRCh38: 17:63968041-63968041
43 SCN4A NM_000334.4(SCN4A):c.845G>A (p.Arg282His) SNV Uncertain significance 579612 rs200615763 GRCh37: 17:62045574-62045574
GRCh38: 17:63968214-63968214
44 SCN4A NM_000334.4(SCN4A):c.82A>C (p.Ile28Leu) SNV Uncertain significance 324554 rs886053250 GRCh37: 17:62050120-62050120
GRCh38: 17:63972760-63972760
45 SCN4A NM_000334.4(SCN4A):c.1559C>G (p.Pro520Arg) SNV Uncertain significance 566952 rs753391449 GRCh37: 17:62041079-62041079
GRCh38: 17:63963719-63963719
46 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4358C>T (p.Ala1453Val) SNV Uncertain significance 888970 GRCh37: 17:62019284-62019284
GRCh38: 17:63941924-63941924
47 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4222C>A (p.Arg1408Ser) SNV Uncertain significance 889025 GRCh37: 17:62020252-62020252
GRCh38: 17:63942892-63942892
48 SCN4A NM_000334.4(SCN4A):c.-67G>A SNV Uncertain significance 889026 GRCh37: 17:62050268-62050268
GRCh38: 17:63972908-63972908
49 SCN4A NM_000334.4(SCN4A):c.1299G>A (p.Leu433=) SNV Uncertain significance 646209 rs759176062 GRCh37: 17:62041981-62041981
GRCh38: 17:63964621-63964621
50 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3679T>C (p.Tyr1227His) SNV Uncertain significance 889158 GRCh37: 17:62022761-62022761
GRCh38: 17:63945401-63945401

UniProtKB/Swiss-Prot genetic disease variations for Hypokalemic Periodic Paralysis, Type 2:

72 (show all 11)
# Symbol AA change Variation ID SNP ID
1 SCN4A p.Arg669His VAR_017788 rs80338784
2 SCN4A p.Arg672Gly VAR_017789 rs80338785
3 SCN4A p.Arg672His VAR_017790 rs80338788
4 SCN4A p.Arg672Ser VAR_017791 rs80338785
5 SCN4A p.Pro1158Ser VAR_017792 rs121908555
6 SCN4A p.Arg222Trp VAR_054935 rs527236148
7 SCN4A p.Arg672Cys VAR_054939 rs80338785
8 SCN4A p.Arg1132Gln VAR_054943 rs80338789
9 SCN4A p.Arg1135His VAR_054944 rs527236150
10 SCN4A p.Arg1129Gln VAR_064987 rs527236149
11 SCN4A p.Arg1135Cys VAR_075434 rs128786334

Expression for Hypokalemic Periodic Paralysis, Type 2

Search GEO for disease gene expression data for Hypokalemic Periodic Paralysis, Type 2.

Pathways for Hypokalemic Periodic Paralysis, Type 2

Pathways related to Hypokalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.25 SCN7A SCN4A
2
Show member pathways
10.83 SCN7A SCN4A
3 10.1 SCN7A SCN4A

GO Terms for Hypokalemic Periodic Paralysis, Type 2

Cellular components related to Hypokalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 voltage-gated sodium channel complex GO:0001518 8.62 SCN7A SCN4A

Biological processes related to Hypokalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of ion transmembrane transport GO:0034765 9.37 SCN7A SCN4A
2 sodium ion transport GO:0006814 9.32 SCN7A SCN4A
3 muscle contraction GO:0006936 9.26 SCN7A SCN4A
4 sodium ion transmembrane transport GO:0035725 9.16 SCN7A SCN4A
5 neuronal action potential GO:0019228 8.96 SCN7A SCN4A
6 membrane depolarization during action potential GO:0086010 8.62 SCN7A SCN4A

Molecular functions related to Hypokalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.32 SCN7A SCN4A
2 voltage-gated ion channel activity GO:0005244 9.26 SCN7A SCN4A
3 cation channel activity GO:0005261 9.16 SCN7A SCN4A
4 sodium channel activity GO:0005272 8.96 SCN7A SCN4A
5 voltage-gated sodium channel activity GO:0005248 8.62 SCN7A SCN4A

Sources for Hypokalemic Periodic Paralysis, Type 2

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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