juvenile Huntington disease

Summary

juvenile Huntington disease (MONDO:0016621) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 24
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.04	Europe	Validated
Point prevalence	1-9 / 1 000 000	0.6	Europe	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000726	Dementia	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0000752	Hyperactivity	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002063	Rigidity	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0002136	Broad-based gait	Frequent (30-79%)
HP:0002500	Abnormal cerebral white matter morphology	Frequent (30-79%)
HP:0012547	Abnormal involuntary eye movements	Frequent (30-79%)
HP:0030190	Oral motor hypotonia	Frequent (30-79%)
HP:0200147	Neuronal loss in basal ganglia	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0002073	Progressive cerebellar ataxia	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0006855	Cerebellar vermis atrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile Huntington disease
Mondo ID	MONDO:0016621
Orphanet	248111
NCIT	C147072
SNOMED CT	230299004
UMLS	C0751208
MedGen	155518
GARD	0010510
Is cancer (heuristic)	no

Also known as: Huntington disease, juvenile onset · JHD · juvenile Huntington chorea · juvenile onset HD

Data availability: 1 GenCC gene-disease record · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › Huntington disease and related disorders › Huntington disease › juvenile Huntington disease

Related subtypes (1): Westphal disease

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 3 · 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
HTT	Definitive	Autosomal dominant	Huntington disease	7
SLC6A4	Definitive	Autosomal dominant	Huntington disease	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HTT	Orphanet:248111	Juvenile Huntington disease
HTT	Orphanet:399	Huntington disease
HTT	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC6A4	HGNC:11050	ENSG00000108576	P31645	Sodium-dependent serotonin transporter	gencc
HTT	HGNC:4851	ENSG00000197386	P42858	Huntingtin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC6A4	Sodium-dependent serotonin transporter	Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle.
HTT	Huntingtin	May play a role in microtubule-mediated transport or vesicle function.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC6A4	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_serotonin_N, SNS_sf
HTT	Other/Unknown	no		Huntingtin, ARM-like, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
jejunal mucosa	1
right lung	1
body of pancreas	1
colonic epithelium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC6A4	162	tissue_specific	marker	right lung, jejunal mucosa, ileal mucosa
HTT	208	ubiquitous	marker	sural nerve, body of pancreas, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HTT	13,156
SLC6A4	2,328

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HTT	P42858	31
SLC6A4	P31645	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Serotonin clearance from the synaptic cleft	1	1427.5×	0.004	SLC6A4
Neurotransmitter clearance	1	634.4×	0.005	SLC6A4
SLC-mediated transport of neurotransmitters	1	203.9×	0.008	SLC6A4
Regulation of MECP2 expression and activity	1	184.2×	0.008	HTT
Transmission across Chemical Synapses	1	38.1×	0.031	SLC6A4
Neuronal System	1	22.1×	0.045	SLC6A4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of serotonin secretion	1	4213.0×	0.003	SLC6A4
obsolete positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity	1	4213.0×	0.003	HTT
regulation of thalamus size	1	4213.0×	0.003	SLC6A4
negative regulation of cerebellar granule cell precursor proliferation	1	2808.7×	0.003	SLC6A4
negative regulation of synaptic transmission, dopaminergic	1	2808.7×	0.003	SLC6A4
positive regulation of CAMKK-AMPK signaling cascade	1	2808.7×	0.003	HTT
regulation of CAMKK-AMPK signaling cascade	1	2106.5×	0.003	HTT
positive regulation of lipophagy	1	1685.2×	0.004	HTT
positive regulation of aggrephagy	1	1404.3×	0.004	HTT
vocal learning	1	1053.2×	0.004	HTT
male mating behavior	1	1053.2×	0.004	SLC6A4
cellular response to cGMP	1	1053.2×	0.004	SLC6A4
conditioned place preference	1	842.6×	0.004	SLC6A4
serotonin uptake	1	766.0×	0.005	SLC6A4
negative regulation of organ growth	1	702.2×	0.005	SLC6A4
obsolete monoamine transport	1	601.9×	0.005	SLC6A4
positive regulation of mitophagy	1	561.7×	0.005	HTT
enteric nervous system development	1	495.6×	0.005	SLC6A4
vasoconstriction	1	443.5×	0.005	SLC6A4
vesicle transport along microtubule	1	443.5×	0.005	HTT
behavioral response to cocaine	1	421.3×	0.005	SLC6A4
synaptic vesicle transport	1	421.3×	0.005	HTT
positive regulation of cilium assembly	1	383.0×	0.006	HTT
brain morphogenesis	1	366.4×	0.006	SLC6A4
membrane depolarization	1	255.3×	0.008	SLC6A4
establishment of mitotic spindle orientation	1	240.7×	0.008	HTT
positive regulation of cell cycle	1	221.7×	0.008	SLC6A4
neurotransmitter transport	1	210.7×	0.008	SLC6A4
negative regulation of extrinsic apoptotic signaling pathway	1	210.7×	0.008	HTT
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	168.5×	0.009	HTT

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC6A4	CETIRIZINE
HTT	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A4	422	4
HTT	165	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	HTT, SLC6A4
CLOTRIMAZOLE	4	HTT, SLC6A4
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	HTT, SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	4	HTT, SLC6A4
CELECOXIB	4	SLC6A4
UMECLIDINIUM	4	SLC6A4
PALONOSETRON	4	SLC6A4
PHENIRAMINE	4	SLC6A4
VILANTEROL	4	SLC6A4
ESCITALOPRAM OXALATE	4	SLC6A4
TIOCONAZOLE	4	SLC6A4
NEFAZODONE HYDROCHLORIDE	4	SLC6A4
ETHYLESTRENOL	4	SLC6A4
CALCIPOTRIENE	4	SLC6A4
CINACALCET HYDROCHLORIDE	4	SLC6A4
CITALOPRAM HYDROBROMIDE	4	SLC6A4
NORGESTIMATE	4	SLC6A4
VENLAFAXINE HYDROCHLORIDE	4	SLC6A4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC6A4	1,055	Binding:1021, Functional:18, ADMET:9, Toxicity:6, Unclassified:1
HTT	77	Binding:72, Functional:5

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SLC6A4	1,055

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLC6A4	1

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	HTT, SLC6A4
CLOTRIMAZOLE	4	HTT, SLC6A4
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	HTT, SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	4	HTT, SLC6A4
CELECOXIB	4	SLC6A4
UMECLIDINIUM	4	SLC6A4
PALONOSETRON	4	SLC6A4
PHENIRAMINE	4	SLC6A4
VILANTEROL	4	SLC6A4
ESCITALOPRAM OXALATE	4	SLC6A4
TIOCONAZOLE	4	SLC6A4
NEFAZODONE HYDROCHLORIDE	4	SLC6A4
ETHYLESTRENOL	4	SLC6A4
CALCIPOTRIENE	4	SLC6A4
CINACALCET HYDROCHLORIDE	4	SLC6A4
CITALOPRAM HYDROBROMIDE	4	SLC6A4
NORGESTIMATE	4	SLC6A4
VENLAFAXINE HYDROCHLORIDE	4	SLC6A4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SLC6A4, HTT
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05707663	Not specified	ACTIVE_NOT_RECRUITING	Longitudinal Assessment of Brain Structure and Function in Juvenile-onset Huntington’s Disease