NRCLP1
MCID: NRC009
MIFTS: 44

Narcolepsy 1 (NRCLP1)

Categories: Eye diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Narcolepsy 1

MalaCards integrated aliases for Narcolepsy 1:

Name: Narcolepsy 1 57 72 29 13 6 70
Narcolepsy-Cataplexy Syndrome 72 70
Narcoleptic Syndrome 1 57 72
Nrclp1 57 72
Narcolepsy-Cataplexy 58
Narcolepsy, Type 1 39
Narcolepsy Type 1 58
Gelineau Disease 58

Characteristics:

Orphanet epidemiological data:

58
narcolepsy type 1
Prevalence: 1-5/10000 (Europe),1-5/10000 (Norway),1-5/10000 (Finland),1-5/10000 (China); Age of onset: Adolescent,Adult,Childhood; Age of death: normal life expectancy;

OMIM®:

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

Miscellaneous:
genetic heterogeneity
onset usually in second decade of life, although earlier and later onset have been reported
prevalence of approximately 1 in 2000 individuals
mutation in the hcrt gene has been identified in 1 patient


HPO:

31
narcolepsy 1:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM® 57 161400
OMIM Phenotypic Series 57 PS161400
MeSH 44 D009290
MESH via Orphanet 45 D009290
ICD10 via Orphanet 33 G47.4
UMLS via Orphanet 71 C0027404 C0751362
Orphanet 58 ORPHA2073
UMLS 70 C0751362 C1834372

Summaries for Narcolepsy 1

OMIM® : 57 Adie (1926) first delineated narcolepsy as a separate and specific entity. It is a sleep disorder characterized by attacks of disabling daytime drowsiness and low alertness. The normal physiologic components of rapid eye movement (REM) sleep, dreaming and loss of muscle tone, are separated and also occur while the subject is awake, resulting in half-sleep dreams and episodes of skeletal muscle paralysis and atonia (cataplexy and sleep paralysis). Unlike normal sleep, that of narcolepsy often begins with REM activity and the time taken to fall asleep is shorter than normal. In contrast to animal models, human narcolepsy is not a simple genetic disorder. Most human cases of narcolepsy are sporadic and carry a specific HLA haplotype (Peyron et al., 2000). Familial cases are the exception rather than the rule, and monozygotic twins show only partial concordance (25 to 31%) (Mignot, 1998). (161400) (Updated 20-May-2021)

MalaCards based summary : Narcolepsy 1, also known as narcolepsy-cataplexy syndrome, is related to hypersomnia and idiopathic hypersomnia, and has symptoms including excessive daytime somnolence and hallucinations, hypnagogic. An important gene associated with Narcolepsy 1 is HCRT (Hypocretin Neuropeptide Precursor), and among its related pathways/superpathways are G-protein signaling N-RAS regulation pathway and MHC class II antigen presentation. Affiliated tissues include eye, skeletal muscle and hypothalamus, and related phenotypes are hallucinations and cataplexy

UniProtKB/Swiss-Prot : 72 Narcolepsy 1: Neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid- eye-movement (REM) sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed.

Related Diseases for Narcolepsy 1

Diseases in the Narcolepsy family:

Narcolepsy 1 Narcolepsy 2
Narcolepsy 3 Narcolepsy 4
Narcolepsy 5 Narcolepsy 6
Narcolepsy 7

Diseases related to Narcolepsy 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 122)
# Related Disease Score Top Affiliating Genes
1 hypersomnia 30.3 HLA-DRB1 HLA-DQB1 HCRT
2 idiopathic hypersomnia 30.0 HLA-DRB1 HLA-DQB1 HCRT
3 acute disseminated encephalomyelitis 29.6 MOG HLA-DRB1 HLA-DQB1 HCRT
4 guillain-barre syndrome 29.6 MOG HLA-DRB1 HLA-DQB1 HCRT
5 narcolepsy 27.4 ZNF365 TNFSF4 P2RY11 MOG HLA-DRB1 HLA-DQB1
6 cerebellar ataxia, deafness, and narcolepsy, autosomal dominant 11.4
7 narcolepsy 7 11.3
8 sleep disorder 10.3
9 autonomic dysfunction 10.2
10 kleine-levin hibernation syndrome 10.2 HLA-DQB1 HCRT
11 recurrent hypersomnia 10.2 HLA-DQB1 HCRT
12 constipation 10.2
13 precocious puberty 10.2
14 seizure disorder 10.2
15 tremor 10.2
16 benign idiopathic neonatal seizures 10.2
17 body mass index quantitative trait locus 1 10.2
18 limbic encephalitis with lgi1 antibodies 10.1 HLA-DRB1 HLA-DQB1
19 autoimmune polyglandular syndrome type 3 10.1 HLA-DRB1 HLA-DQB1
20 htlv-1 associated myelopathy/tropical spastic paraparesis 10.1 HLA-DRB1 HLA-DQB1
21 latent autoimmune diabetes in adults 10.1 HLA-DRB1 HLA-DQB1
22 occupational asthma 10.1 HLA-DRB1 HLA-DQB1
23 primary adrenal insufficiency 10.1 HLA-DRB1 HLA-DQB1
24 recurrent respiratory papillomatosis 10.1 HLA-DRB1 HLA-DQB1
25 autoimmune disease 10.1
26 schizophrenia 10.1
27 restless legs syndrome 10.1
28 amnestic disorder 10.1
29 epilepsy 10.1
30 chronic pain 10.1
31 beryllium disease 10.1 HLA-DRB1 HLA-DQB1
32 apple allergy 10.1 HLA-DRB1 HLA-DQB1
33 helix syndrome 10.1
34 rem sleep behavior disorder 10.1
35 rare sleep disorder 10.1
36 chronic beryllium disease 10.1 HLA-DRB1 HLA-DQB1
37 metal allergy 10.1 HLA-DRB1 HLA-DQB1
38 autoimmune hepatitis type 1 10.1 HLA-DRB1 HLA-DQB1
39 focal epithelial hyperplasia 10.1 HLA-DRB1 HLA-DQB1
40 podoconiosis 10.1 HLA-DRB1 HLA-DQB1
41 pemphigoid 10.1 HLA-DRB1 HLA-DQB1
42 osteonecrosis of the jaw 10.0 HLA-DRB1 HLA-DQB1
43 pityriasis rosea 10.0 HLA-DRB1 HLA-DQB1
44 oligoarticular juvenile idiopathic arthritis 10.0 HLA-DRB1 HLA-DQB1
45 idiopathic nephrotic syndrome 10.0 HLA-DRB1 HLA-DQB1
46 ocular cicatricial pemphigoid 10.0 HLA-DRB1 HLA-DQB1
47 cicatricial pemphigoid 10.0 HLA-DRB1 HLA-DQB1
48 alveolar echinococcosis 10.0 HLA-DRB1 HLA-DQB1
49 paraneoplastic pemphigus 10.0 HLA-DRB1 HLA-DQB1
50 cytomegalovirus retinitis 10.0 HLA-DRB1 HLA-DQB1

Graphical network of the top 20 diseases related to Narcolepsy 1:



Diseases related to Narcolepsy 1

Symptoms & Phenotypes for Narcolepsy 1

Human phenotypes related to Narcolepsy 1:

58 31 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hallucinations 58 31 hallmark (90%) Very frequent (99-80%) HP:0000738
2 cataplexy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002524
3 transient global amnesia 58 31 hallmark (90%) Very frequent (99-80%) HP:0010534
4 excessive daytime somnolence 31 hallmark (90%) HP:0001262
5 abnormality of vision 58 31 frequent (33%) Frequent (79-30%) HP:0000504
6 abnormal rapid eye movement sleep 58 31 frequent (33%) Frequent (79-30%) HP:0002494
7 slurred speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0001350
8 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
9 syncope 58 31 occasional (7.5%) Occasional (29-5%) HP:0001279
10 sleep disturbance 58 Very frequent (99-80%)
11 abnormality of the eye 58 Frequent (79-30%)
12 narcolepsy 31 HP:0030050
13 excessive daytime sleepiness 58 Very frequent (99-80%)
14 paroxysmal drowsiness 31 HP:0002330
15 hypnagogic hallucinations 31 HP:0002519
16 hypnopompic hallucinations 31 HP:0006896

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
excessive daytime sleepiness
hypnagogic hallucinations
hypnopompic hallucinations
cataplexy, paroxysmal weakness or paralysis
cataplexy often triggered by strong emotions
more
Laboratory Abnormalities:
hla-dqw6 association (dqb1*0602)
decreased levels of csf hypocretin (hcrt, )

Growth Weight:
rapid weight gain may occur

Clinical features from OMIM®:

161400 (Updated 20-May-2021)

UMLS symptoms related to Narcolepsy 1:


excessive daytime somnolence; hallucinations, hypnagogic

Drugs & Therapeutics for Narcolepsy 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-994 in Patients With Narcolepsy With or Without Cataplexy (Narcolepsy Type 1 or Narcolepsy Type 2) Recruiting NCT04096560 Phase 2 TAK-994;Placebo
2 A Dose-Blind Extension Study With Double-blind, Placebo-Controlled, Randomized Withdrawal Period to Evaluate the Safety and Explore the Pharmacokinetics and Pharmacodynamics of TAK-994 in Adults With Narcolepsy With Cataplexy (Narcolepsy Type 1) Not yet recruiting NCT04820842 Phase 2 TAK-994;Placebo
3 The Role of the Circadian System in Neurological Sleep-wake Disorders: Assessment of Circadian and Homeostatic Sleep-wake Regulation and Vigilance With a Poly-nap Protocol Completed NCT03356938
4 Microglial Activation in Narcolepsy Type 1 and Kleine-Levin Syndrome: Positron Emission Tomography (PET) Study in [18F] DPA-714 Recruiting NCT03754348
5 A Study to Assess the Frequency and Characteristics of Wake and Sleep State Transitions Over Multiple Nights in Subjects With Narcolepsy Type 1 Compared With Healthy Subjects Using a Portable Electroencephalogram Device Recruiting NCT04445129

Search NIH Clinical Center for Narcolepsy 1

Genetic Tests for Narcolepsy 1

Genetic tests related to Narcolepsy 1:

# Genetic test Affiliating Genes
1 Narcolepsy 1 29 HCRT

Anatomical Context for Narcolepsy 1

MalaCards organs/tissues related to Narcolepsy 1:

40
Eye, Skeletal Muscle, Hypothalamus, T Cells, Heart, Ovary, Temporal Lobe

Publications for Narcolepsy 1

Articles related to Narcolepsy 1:

(show top 50) (show all 53)
# Title Authors PMID Year
1
A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. 6 57
10973318 2000
2
T cells in patients with narcolepsy target self-antigens of hypocretin neurons. 57
30232458 2018
3
A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. 6
21907016 2011
4
Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. 57
20711174 2010
5
Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin treatment. 57
19841387 2009
6
Narp immunostaining of human hypocretin (orexin) neurons: loss in narcolepsy. 57
16135770 2005
7
Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. 57
16247044 2005
8
A functional autoantibody in narcolepsy. 57
15589310 2004
9
CSF hypocretin-1 (orexin-A) levels in childhood narcolepsy and neurologic disorders. 57
15623725 2004
10
A monozygotic twin pair discordant for narcolepsy and CSF hypocretin-1. 57
15184641 2004
11
Monozygotic twins concordant for narcolepsy-cataplexy without any detectable abnormality in the hypocretin (orexin) pathway. 57
15081654 2004
12
Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy. 57
14769912 2004
13
Age at onset of narcolepsy in two large populations of patients in France and Quebec. 57
11739821 2001
14
Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients. 57
11425946 2001
15
Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. 57
11179016 2001
16
Reduced number of hypocretin neurons in human narcolepsy. 57
11055430 2000
17
Hypocretin (orexin) deficiency in human narcolepsy. 57
10615891 2000
18
Let sleeping dogs lie? 57
10471483 1999
19
Narcolepsy: a key role for hypocretins (orexins) 57
10481905 1999
20
Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. 57
10481909 1999
21
The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. 57
10458611 1999
22
Genetic studies in narcolepsy, a disorder affecting REM sleep. 57
9987919 1999
23
Genetic and familial aspects of narcolepsy. 57
9484418 1998
24
The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. 57
9419374 1998
25
HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. 57
9456467 1997
26
Pharmacological aspects of human and canine narcolepsy. 57
9185233 1997
27
Autonomic nervous system function in narcolepsy. 57
10607117 1994
28
DQ (rather than DR) gene marks susceptibility to narcolepsy. 57
1349071 1992
29
Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment. 57
1673032 1991
30
Genetic heterogeneity in narcolepsy. 57
1969083 1990
31
Familial patterns of narcolepsy. 57
2574313 1989
32
Restriction fragment length polymorphism in canine narcolepsy. 57
2563354 1989
33
Narcolepsy-cataplexy in Israeli Jews is associated exclusively with the HLA DR2 haplotype. A study at the serological and genomic level. 57
2896649 1988
34
HLA and narcolepsy in a German population. 57
3641479 1986
35
Human histocompatibility leukocyte antigen (HLA) haplotype frequencies estimated from the data on HLA class I, II, and III antigens in 111 Japanese narcoleptics. 57
3865934 1985
36
HLA antigens in Japanese patients with narcolepsy. All the patients were DR2 positive. 57
6597978 1984
37
Genetic markers in narcolepsy. 57
6150235 1984
38
Canine model of narcolepsy: genetic and developmental determinants. 57
7199479 1982
39
Genetic factors in canine narcolepsy. 57
574310 1979
40
Genetic study of narcoleptic syndrome. 57
712757 1978
41
The inheritance of diurnal sleepiness as measured by pupillography. 57
5425102 1970
42
The pupillogram and narcolepsy. A method to measure decreased levels of wakefulness. 57
5387594 1969
43
Hereditary cataplexy. 57
6062995 1967
44
Excessive daytime sleepiness in cancer patients. 61
32939599 2020
45
A comparative study of methods for automatic detection of rapid eye movement abnormal muscular activity in narcolepsy. 61
29530376 2018
46
Prevalence of sleep disorders among ESRD patients. 61
25959021 2015
47
Characteristics of REM sleep behavior disorder in childhood. 61
22505856 2012
48
Outcomes of CPAP treatment in a sleep laboratory specialized in neuropsychiatry. 61
15611589 2004
49
Sleep disturbance in chronic fatigue syndrome. 61
8510058 1993
50
The multiple sleep latency test in the diagnosis of sleep disorders. 61
2296743 1990

Variations for Narcolepsy 1

ClinVar genetic disease variations for Narcolepsy 1:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HCRT NM_001524.1(HCRT):c.47T>G (p.Leu16Arg) SNV Pathogenic 7303 rs104894574 GRCh37: 17:40336521-40336521
GRCh38: 17:42184503-42184503
2 MOG NM_206809.4(MOG):c.398C>G (p.Ser133Cys) SNV Pathogenic 29798 rs387906655 GRCh37: 6:29627405-29627405
GRCh38: 6:29659628-29659628
3 NPC1 NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala) SNV Pathogenic 2966 rs80358257 GRCh37: 18:21118528-21118528
GRCh38: 18:23538564-23538564
4 NPC1 NM_000271.5(NPC1):c.1421C>T (p.Pro474Leu) SNV Pathogenic 374049 rs372445155 GRCh37: 18:21134854-21134854
GRCh38: 18:23554890-23554890
5 MOG NM_206809.4(MOG):c.88+18dup Duplication Benign 931819 GRCh37: 6:29625084-29625085
GRCh38: 6:29657307-29657308

UniProtKB/Swiss-Prot genetic disease variations for Narcolepsy 1:

72
# Symbol AA change Variation ID SNP ID
1 HCRT p.Leu16Arg VAR_011633 rs104894574

Expression for Narcolepsy 1

Search GEO for disease gene expression data for Narcolepsy 1.

Pathways for Narcolepsy 1

Pathways related to Narcolepsy 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.91 HLA-DRB1 HLA-DQB1
2 10.81 HLA-DRB1 HLA-DQB1 CTSH

GO Terms for Narcolepsy 1

Cellular components related to Narcolepsy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosomal membrane GO:0005765 9.54 NPC1 HLA-DRB1 HLA-DQB1
2 endocytic vesicle membrane GO:0030666 9.43 HLA-DRB1 HLA-DQB1
3 ER to Golgi transport vesicle membrane GO:0012507 9.4 HLA-DRB1 HLA-DQB1
4 transport vesicle membrane GO:0030658 9.32 HLA-DRB1 HLA-DQB1
5 clathrin-coated endocytic vesicle membrane GO:0030669 9.26 HLA-DRB1 HLA-DQB1
6 integral component of lumenal side of endoplasmic reticulum membrane GO:0071556 9.16 HLA-DRB1 HLA-DQB1
7 MHC class II protein complex GO:0042613 8.96 HLA-DRB1 HLA-DQB1
8 lysosome GO:0005764 8.92 NPC1 HLA-DRB1 HLA-DQB1 CTSH

Biological processes related to Narcolepsy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 T cell receptor signaling pathway GO:0050852 9.54 HLA-DQB1 HLA-DRB1 MOG
2 phospholipase C-activating G protein-coupled receptor signaling pathway GO:0007200 9.43 HCRT P2RY11
3 negative regulation of interferon-gamma production GO:0032689 9.4 HLA-DRB1 TNFSF4
4 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II GO:0002504 9.32 HLA-DQB1 HLA-DRB1
5 positive regulation of memory T cell differentiation GO:0043382 9.26 HLA-DRB1 TNFSF4
6 humoral immune response mediated by circulating immunoglobulin GO:0002455 9.16 HLA-DQB1 HLA-DRB1
7 immunoglobulin production involved in immunoglobulin mediated immune response GO:0002381 8.96 HLA-DQB1 HLA-DRB1
8 antigen processing and presentation GO:0019882 8.8 CTSH HLA-DQB1 HLA-DRB1

Molecular functions related to Narcolepsy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptide antigen binding GO:0042605 8.96 HLA-DRB1 HLA-DQB1
2 MHC class II receptor activity GO:0032395 8.62 HLA-DRB1 HLA-DQB1

Sources for Narcolepsy 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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