HKPX3
MCID: HYP519
MIFTS: 34

Hyperekplexia 3 (HKPX3)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Hyperekplexia 3

MalaCards integrated aliases for Hyperekplexia 3:

Name: Hyperekplexia 3 57 12 72 29 13 6 15 70
Hkpx3 57 12 72
Hyperekplexia, Type 3 39

Characteristics:

OMIM®:

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

Miscellaneous:
onset in infancy
some patients have resolution of symptoms in first year of life


HPO:

31
hyperekplexia 3:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0060698
OMIM® 57 614618
OMIM Phenotypic Series 57 PS149400
MeSH 44 D000071017
ICD10 32 G25.8
UMLS 70 C3553288

Summaries for Hyperekplexia 3

UniProtKB/Swiss-Prot : 72 Hyperekplexia 3: A neurologic disorder characterized by neonatal hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life- threatening neonatal apnea episodes. Notably, in some cases, symptoms resolved in the first year of life.

MalaCards based summary : Hyperekplexia 3, also known as hkpx3, is related to brittle cornea syndrome 2 and periodic limb movement disorder, and has symptoms including muscular stiffness An important gene associated with Hyperekplexia 3 is SLC6A5 (Solute Carrier Family 6 Member 5), and among its related pathways/superpathways are Synaptic vesicle cycle and NRF2 pathway. Related phenotypes are hypertonia and muscle stiffness

Disease Ontology : 12 A hyperekplexia that has material basis in homozygous or compound heterozygous mutation in the SLC6A5 gene on chromosome 11p15.

More information from OMIM: 614618 PS149400

Related Diseases for Hyperekplexia 3

Diseases in the Hyperekplexia family:

Hyperekplexia 1 Hyperekplexia 3
Hyperekplexia 2 Hyperekplexia 4
Sporadic Hyperekplexia

Diseases related to Hyperekplexia 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 brittle cornea syndrome 2 9.9 SLC6A5 PRDM5
2 periodic limb movement disorder 9.8 SLC6A5 GLRA1
3 glycine encephalopathy 9.7 SLC6A9 SLC6A5 GLRA1
4 hartnup disorder 9.6 SLC6A5 SLC38A8
5 hyperekplexia 9.5 SLC6A9 SLC6A5 SLC6A17 GLRA1
6 retinitis pigmentosa 68 9.4 SLC7A13 SLC6A17 SLC38A8
7 developmental and epileptic encephalopathy 3 9.2 SLC7A13 SLC6A9 SLC6A17 SLC38A8

Graphical network of the top 20 diseases related to Hyperekplexia 3:



Diseases related to Hyperekplexia 3

Symptoms & Phenotypes for Hyperekplexia 3

Human phenotypes related to Hyperekplexia 3:

31
# Description HPO Frequency HPO Source Accession
1 hypertonia 31 HP:0001276
2 muscle stiffness 31 HP:0003552
3 apnea 31 HP:0002104
4 exaggerated startle response 31 HP:0002267

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Muscle Soft Tissue:
muscle stiffness
hypertonia, neonatal

Respiratory:
apneic episodes, neonatal
breath-holding episodes, infancy

Neurologic Central Nervous System:
hypertonicity
exaggerated startle response (to tactile or acoustic stimuli)

Clinical features from OMIM®:

614618 (Updated 20-May-2021)

UMLS symptoms related to Hyperekplexia 3:


muscular stiffness

Drugs & Therapeutics for Hyperekplexia 3

Search Clinical Trials , NIH Clinical Center for Hyperekplexia 3

Genetic Tests for Hyperekplexia 3

Genetic tests related to Hyperekplexia 3:

# Genetic test Affiliating Genes
1 Hyperekplexia 3 29 SLC6A5

Anatomical Context for Hyperekplexia 3

Publications for Hyperekplexia 3

Articles related to Hyperekplexia 3:

# Title Authors PMID Year
1
Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. 57 6
16751771 2006
2
Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease. 6
22700964 2012
3
Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. 6
14622583 2003
4
Case report of a PRDM5 linked brittle cornea syndrome type 2 in association with a novel SLC6A5 mutation. 61
33120686 2020

Variations for Hyperekplexia 3

ClinVar genetic disease variations for Hyperekplexia 3:

6 (show top 50) (show all 68)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC6A5 NM_004211.5(SLC6A5):c.1530T>G (p.Ser510Arg) SNV Pathogenic 31540 rs281864926 GRCh37: 11:20652267-20652267
GRCh38: 11:20630721-20630721
2 SLC6A5 NM_004211.5(SLC6A5):c.1444T>C (p.Trp482Arg) SNV Pathogenic 38370 rs281864925 GRCh37: 11:20649574-20649574
GRCh38: 11:20628028-20628028
3 SLC6A5 NM_004211.5(SLC6A5):c.323del (p.Pro108fs) Deletion Pathogenic 38371 rs281864923 GRCh37: 11:20622990-20622990
GRCh38: 11:20601444-20601444
4 SLC6A5 NM_004211.5(SLC6A5):c.571C>T (p.Arg191Ter) SNV Pathogenic 579017 rs376783257 GRCh37: 11:20625862-20625862
GRCh38: 11:20604316-20604316
5 SLC6A5 NM_004211.5(SLC6A5):c.808C>T (p.Gln270Ter) SNV Pathogenic 658045 rs778603956 GRCh37: 11:20628681-20628681
GRCh38: 11:20607135-20607135
6 SLC6A5 NM_004211.5(SLC6A5):c.187C>T (p.Gln63Ter) SNV Pathogenic 1034063 GRCh37: 11:20622858-20622858
GRCh38: 11:20601312-20601312
7 SLC6A5 NM_004211.5(SLC6A5):c.1315C>T (p.Arg439Ter) SNV Pathogenic 1028703 GRCh37: 11:20648308-20648308
GRCh38: 11:20626762-20626762
8 SLC6A5 NM_004211.5(SLC6A5):c.1274C>T (p.Thr425Met) SNV Pathogenic 5767 rs121908498 GRCh37: 11:20648267-20648267
GRCh38: 11:20626721-20626721
9 SLC6A5 NM_004211.5(SLC6A5):c.1526A>G (p.Asn509Ser) SNV Pathogenic 5766 rs121908497 GRCh37: 11:20652263-20652263
GRCh38: 11:20630717-20630717
10 SLC6A5 NM_004211.5(SLC6A5):c.916C>G (p.Leu306Val) SNV Pathogenic 5765 rs121908496 GRCh37: 11:20629129-20629129
GRCh38: 11:20607583-20607583
11 SLC6A5 NM_004211.5(SLC6A5):c.1888C>T (p.Gln630Ter) SNV Pathogenic 5764 rs121908495 GRCh37: 11:20660023-20660023
GRCh38: 11:20638477-20638477
12 SLC6A5 NM_004211.5(SLC6A5):c.1472A>G (p.Tyr491Cys) SNV Pathogenic 5763 rs121908494 GRCh37: 11:20649602-20649602
GRCh38: 11:20628056-20628056
13 SLC6A5 NM_004211.5(SLC6A5):c.1294delinsTT (p.Val432fs) Indel Pathogenic 5762 rs281864924 GRCh37: 11:20648287-20648287
GRCh38: 11:20626741-20626741
14 SLC6A5 NM_004211.5(SLC6A5):c.1131C>A (p.Tyr377Ter) SNV Pathogenic 5761 rs121908493 GRCh37: 11:20639301-20639301
GRCh38: 11:20617755-20617755
15 SLC6A5 NM_004211.5(SLC6A5):c.1640T>C (p.Phe547Ser) SNV Pathogenic/Likely pathogenic 540366 rs772652517 GRCh37: 11:20657868-20657868
GRCh38: 11:20636322-20636322
16 SLC6A5 NM_004211.5(SLC6A5):c.679+1G>A SNV Likely pathogenic 652178 rs1590154255 GRCh37: 11:20625971-20625971
GRCh38: 11:20604425-20604425
17 SLC6A5 NM_004211.5(SLC6A5):c.1910C>T (p.Ala637Val) SNV Uncertain significance 656330 rs770169307 GRCh37: 11:20660045-20660045
GRCh38: 11:20638499-20638499
18 SLC6A5 NM_004211.5(SLC6A5):c.1346G>A (p.Gly449Glu) SNV Uncertain significance 1028704 GRCh37: 11:20648339-20648339
GRCh38: 11:20626793-20626793
19 SLC6A5 NM_004211.5(SLC6A5):c.1738-8G>A SNV Uncertain significance 1028705 GRCh37: 11:20658710-20658710
GRCh38: 11:20637164-20637164
20 SLC6A5 NM_004211.5(SLC6A5):c.1846A>G (p.Met616Val) SNV Uncertain significance 854760 GRCh37: 11:20658826-20658826
GRCh38: 11:20637280-20637280
21 SLC6A5 NM_004211.5(SLC6A5):c.1913C>T (p.Ser638Phe) SNV Uncertain significance 581456 rs753023936 GRCh37: 11:20660048-20660048
GRCh38: 11:20638502-20638502
22 SLC6A5 NM_004211.5(SLC6A5):c.2296C>T (p.Arg766Cys) SNV Uncertain significance 580240 rs141654146 GRCh37: 11:20676316-20676316
GRCh38: 11:20654770-20654770
23 SLC6A5 NM_004211.5(SLC6A5):c.1736T>C (p.Met579Thr) SNV Uncertain significance 565407 rs761723711 GRCh37: 11:20657964-20657964
GRCh38: 11:20636418-20636418
24 SLC6A5 NM_004211.5(SLC6A5):c.2186T>C (p.Ile729Thr) SNV Uncertain significance 304036 rs142855098 GRCh37: 11:20673950-20673950
GRCh38: 11:20652404-20652404
25 SLC6A5 NM_004211.5(SLC6A5):c.52G>C (p.Glu18Gln) SNV Uncertain significance 1037924 GRCh37: 11:20622723-20622723
GRCh38: 11:20601177-20601177
26 SLC6A5 NM_004211.5(SLC6A5):c.1133T>C (p.Phe378Ser) SNV Uncertain significance 1041277 GRCh37: 11:20639303-20639303
GRCh38: 11:20617757-20617757
27 SLC6A5 NM_004211.5(SLC6A5):c.194C>A (p.Ala65Glu) SNV Uncertain significance 1045815 GRCh37: 11:20622865-20622865
GRCh38: 11:20601319-20601319
28 SLC6A5 NC_000011.9:g.(?_20621199)_(20676434_?)dup Duplication Uncertain significance 1054321 GRCh37: 11:20621199-20676434
GRCh38:
29 SLC6A5 NM_004211.5(SLC6A5):c.76C>T (p.Pro26Ser) SNV Uncertain significance 1060018 GRCh37: 11:20622747-20622747
GRCh38: 11:20601201-20601201
30 SLC6A5 NM_004211.5(SLC6A5):c.1171G>A (p.Glu391Lys) SNV Uncertain significance 1025839 GRCh37: 11:20639341-20639341
GRCh38: 11:20617795-20617795
31 SLC6A5 NM_004211.5(SLC6A5):c.340C>T (p.Pro114Ser) SNV Uncertain significance 1013650 GRCh37: 11:20623011-20623011
GRCh38: 11:20601465-20601465
32 SLC6A5 NM_004211.5(SLC6A5):c.2070+1G>A SNV Uncertain significance 632158 rs770660705 GRCh37: 11:20668481-20668481
GRCh38: 11:20646935-20646935
33 SLC6A5 NM_004211.5(SLC6A5):c.1969+4A>T SNV Uncertain significance 643116 rs1476186922 GRCh37: 11:20660108-20660108
GRCh38: 11:20638562-20638562
34 SLC6A5 NM_004211.5(SLC6A5):c.1169G>T (p.Gly390Val) SNV Uncertain significance 304017 rs140296233 GRCh37: 11:20639339-20639339
GRCh38: 11:20617793-20617793
35 SLC6A5 NM_004211.5(SLC6A5):c.4-11T>C SNV Uncertain significance 303993 rs774039277 GRCh37: 11:20622664-20622664
GRCh38: 11:20601118-20601118
36 SLC6A5 NM_004211.5(SLC6A5):c.683C>A (p.Ala228Asp) SNV Uncertain significance 540364 rs371265931 GRCh37: 11:20628556-20628556
GRCh38: 11:20607010-20607010
37 SLC6A5 NM_004211.5(SLC6A5):c.811+3G>A SNV Uncertain significance 540365 rs1555039131 GRCh37: 11:20628687-20628687
GRCh38: 11:20607141-20607141
38 SLC6A5 NM_004211.5(SLC6A5):c.1735A>C (p.Met579Leu) SNV Uncertain significance 836222 GRCh37: 11:20657963-20657963
GRCh38: 11:20636417-20636417
39 SLC6A5 NM_004211.5(SLC6A5):c.307G>A (p.Ala103Thr) SNV Uncertain significance 842751 GRCh37: 11:20622978-20622978
GRCh38: 11:20601432-20601432
40 SLC6A5 NM_004211.5(SLC6A5):c.2167G>A (p.Ala723Thr) SNV Uncertain significance 856746 GRCh37: 11:20673931-20673931
GRCh38: 11:20652385-20652385
41 SLC6A5 NM_004211.5(SLC6A5):c.1624+9C>T SNV Uncertain significance 880207 GRCh37: 11:20652370-20652370
GRCh38: 11:20630824-20630824
42 SLC6A5 NM_004211.5(SLC6A5):c.299C>T (p.Ala100Val) SNV Uncertain significance 935611 GRCh37: 11:20622970-20622970
GRCh38: 11:20601424-20601424
43 SLC6A5 NM_004211.5(SLC6A5):c.1286C>A (p.Pro429Gln) SNV Uncertain significance 942453 GRCh37: 11:20648279-20648279
GRCh38: 11:20626733-20626733
44 SLC6A5 NM_004211.5(SLC6A5):c.98G>C (p.Arg33Thr) SNV Uncertain significance 950358 GRCh37: 11:20622769-20622769
GRCh38: 11:20601223-20601223
45 SLC6A5 NM_004211.5(SLC6A5):c.1668G>T (p.Arg556Ser) SNV Uncertain significance 955154 GRCh37: 11:20657896-20657896
GRCh38: 11:20636350-20636350
46 SLC6A5 NM_004211.5(SLC6A5):c.242A>G (p.Lys81Arg) SNV Uncertain significance 958611 GRCh37: 11:20622913-20622913
GRCh38: 11:20601367-20601367
47 SLC6A5 NM_004211.5(SLC6A5):c.59C>T (p.Ala20Val) SNV Uncertain significance 303994 rs200496125 GRCh37: 11:20622730-20622730
GRCh38: 11:20601184-20601184
48 SLC6A5 NM_004211.5(SLC6A5):c.134C>G (p.Ala45Gly) SNV Likely benign 303998 rs755131121 GRCh37: 11:20622805-20622805
GRCh38: 11:20601259-20601259
49 SLC6A5 NM_004211.5(SLC6A5):c.950C>T (p.Thr317Met) SNV Likely benign 304015 rs150764554 GRCh37: 11:20629163-20629163
GRCh38: 11:20607617-20607617
50 SLC6A5 NM_004211.5(SLC6A5):c.2306G>A (p.Arg769His) SNV Likely benign 304041 rs75450512 GRCh37: 11:20676326-20676326
GRCh38: 11:20654780-20654780

UniProtKB/Swiss-Prot genetic disease variations for Hyperekplexia 3:

72
# Symbol AA change Variation ID SNP ID
1 SLC6A5 p.Leu306Val VAR_044168 rs121908496
2 SLC6A5 p.Thr425Met VAR_044169 rs121908498
3 SLC6A5 p.Trp482Cys VAR_044171
4 SLC6A5 p.Tyr491Cys VAR_044172 rs121908494
5 SLC6A5 p.Asn509Ser VAR_044174 rs121908497
6 SLC6A5 p.Ser510Arg VAR_044175 rs281864926
7 SLC6A5 p.Pro429Leu VAR_082588 rs745539706

Expression for Hyperekplexia 3

Search GEO for disease gene expression data for Hyperekplexia 3.

Pathways for Hyperekplexia 3

Pathways related to Hyperekplexia 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.07 SLC6A9 SLC6A5
2 10.96 SLC6A9 SLC6A5 SLC6A17

GO Terms for Hyperekplexia 3

Cellular components related to Hyperekplexia 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.85 SLC7A13 SLC6A9 SLC6A5 SLC6A17 SLC38A8 GLRA1
2 integral component of plasma membrane GO:0005887 9.62 SLC6A9 SLC6A5 SLC6A17 GLRA1
3 integral component of synaptic vesicle membrane GO:0030285 9.26 SLC6A9 SLC6A17
4 dense core granule GO:0031045 9.16 SLC6A9 SLC6A5
5 glycinergic synapse GO:0098690 8.96 SLC6A5 GLRA1
6 integral component of presynaptic membrane GO:0099056 8.8 SLC6A9 SLC6A5 GLRA1

Biological processes related to Hyperekplexia 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sodium ion transmembrane transport GO:0035725 9.58 SLC6A9 SLC6A5 SLC6A17
2 amino acid transport GO:0006865 9.5 SLC7A13 SLC6A9 SLC38A8
3 neurotransmitter transport GO:0006836 9.43 SLC6A9 SLC6A5 SLC6A17
4 synaptic transmission, glycinergic GO:0060012 9.37 SLC6A5 GLRA1
5 amino acid transmembrane transport GO:0003333 9.33 SLC7A13 SLC6A9 SLC38A8
6 glycine import across plasma membrane GO:1903804 8.96 SLC6A9 SLC6A5
7 glycine transport GO:0015816 8.8 SLC6A9 SLC6A5 SLC6A17

Molecular functions related to Hyperekplexia 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 symporter activity GO:0015293 9.33 SLC6A9 SLC6A5 SLC6A17
2 glycine transmembrane transporter activity GO:0015187 8.96 SLC6A9 SLC6A5
3 glycine:sodium symporter activity GO:0015375 8.62 SLC6A9 SLC6A5

Sources for Hyperekplexia 3

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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