Narcolepsy 1

Summary

Narcolepsy 1 (MONDO:0008062) is a disease with 1 cohort gene and 3 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	narcolepsy 1
Mondo ID	MONDO:0008062
MeSH	C563534
OMIM	161400
NCIT	C84618
SNOMED CT	46263000
UMLS	C1834372
MedGen	371809
GARD	0015091
Is cancer (heuristic)	no

Also known as: HCRT narcolepsy · narcolepsy 1 · narcolepsy caused by mutation in HCRT · NRCLP1

Data availability: 1 ClinVar variant · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › narcolepsy-cataplexy syndrome › narcolepsy 1

Related subtypes (2): narcolepsy 3, narcolepsy 7

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7303	NM_001524.1(HCRT):c.47T>G (p.Leu16Arg)	HCRT	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HCRT	Limited	Autosomal dominant	narcolepsy 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HCRT	Orphanet:2073	Narcolepsy type 1
HCRT	Orphanet:83465	Narcolepsy type 2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HCRT	HGNC:4847	ENSG00000161610	O43612	Hypocretin neuropeptide precursor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HCRT	Hypocretin neuropeptide precursor	Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HCRT	Other/Unknown	no		Orexin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hypothalamus	1
pancreatic ductal cell	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HCRT	90		marker	hypothalamus, pancreatic ductal cell, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HCRT	1,623

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HCRT	O43612	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Orexin and neuropeptides FF and QRFP bind to their respective receptors	1	1142.0×	0.002	HCRT
G alpha (q) signalling events	1	57.4×	0.017	HCRT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sleep	1	2407.4×	0.003	HCRT
negative regulation of transmission of nerve impulse	1	2407.4×	0.003	HCRT
positive regulation of transmission of nerve impulse	1	2407.4×	0.003	HCRT
negative regulation of potassium ion transport	1	1872.4×	0.003	HCRT
behavioral response to ethanol	1	1203.7×	0.003	HCRT
response to peptide	1	1123.5×	0.003	HCRT
drinking behavior	1	991.3×	0.003	HCRT
negative regulation of DNA replication	1	887.0×	0.003	HCRT
regulation of neurotransmitter secretion	1	766.0×	0.003	HCRT
temperature homeostasis	1	648.1×	0.003	HCRT
eating behavior	1	601.9×	0.003	HCRT
positive regulation of calcium ion transport	1	581.1×	0.003	HCRT
response to starvation	1	468.1×	0.003	HCRT
excitatory postsynaptic potential	1	443.5×	0.003	HCRT
neuropeptide signaling pathway	1	172.0×	0.007	HCRT
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	HCRT
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.008	HCRT
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.009	HCRT
chemical synaptic transmission	1	77.3×	0.013	HCRT

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HCRT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HCRT

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HCRT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03356938	Not specified	COMPLETED	The Role of the Circadian System in Neurological Sleep-wake Disorders
NCT03754348	Not specified	COMPLETED	Microglial Activation in Narcolepsy Type 1 and Kleine-Levin Syndrome: Positron Emission Tomography (PET) Study in [18F] DPA-714
NCT04419792	Not specified	SUSPENDED	‘A Profile of Physical Performance Variables in an Out-patient Adult Population With Narcolepsy’