HTT
Chr 4ADARhuntingtin
Also known as: HD, IT15, LOMARS
Huntington disease is caused by an expanded CAG repeat in exon 1 of HTT: 26 or fewer repeats is normal, 27–35 intermediate (no symptoms, but able to expand in a child), 36–39 reduced penetrance, and 40 or more diagnostic. Repeats above about 60 present as juvenile HD, and large expansions arise almost only through the father.
Repeat length explains only part of the age at onset. No disease-modifying treatment is licensed; the approved drugs treat chorea. Testing is a dedicated repeat test.
Primary Disease Associations & Inheritance
Clinical highlights
- Definitive · Huntington disease · AD · ClinGen 2021
- Strong · Lopes-Maciel-Rodan syndrome · AR · Labcorp Genetics (formerly Invitae)
- Supportive · juvenile Huntington disease · AD · Orphanet
- tominersenASOPhase 2
Lowers total huntingtin.
Delivery: IntrathecalEarlier phase 3 paused; dose/population re-evaluation ongoing
- AMT-130AAV gene therapyPhase 1/2
One-time delivery of a microRNA lowering (mutant) huntingtin.
Delivery: Stereotactic intrastriatal
Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.
ClinicalTrials.govHTT is a repeat-expansion gene
CAG repeat in exon 1 (a polyglutamine tract) — the cause of Huntington disease. What matters is the number of repeats.
- Normal · ≤26
- Intermediate · 27–35 — no symptoms, but can expand into the disease range in a child, mainly when passed on by the father
- Reduced penetrance · 36–39 — some carriers develop HD, others stay well into old age
- Full penetrance · ≥40 — diagnostic of Huntington disease
Repeats above about 60 present as juvenile HD. Repeat length explains only part of the age at onset, and large jumps in size happen almost only through the father.
Testing: Sequencing does not size this repeat; order the HD repeat test. An apparently homozygous normal result should be checked by triplet-primed PCR or Southern blot, which find a large expansion that standard PCR misses.
Sources: ACMG points to consider 2026 (Table 1); EMQN best-practice guidelines (Losekoot 2013).
ClinVar Variant Classifications
0 submitted variants in ClinVar
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease
RECRUITINGDevelopment of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
RECRUITINGA Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
RECRUITINGA Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease
ACTIVE NOT RECRUITINGSafety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease
ACTIVE NOT RECRUITINGA Study to Evaluate AB-1001 Striatal Administration in Adults With Early Manifest Huntington's Disease
ACTIVE NOT RECRUITINGBiology-Driven Cognitive Profiling in Huntington's Disease
ACTIVE NOT RECRUITINGStudy of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease
RECRUITINGHDClarity: a Multi-site Cerebrospinal Fluid Collection Initiative to Facilitate Therapeutic Development for Huntington's Disease
RECRUITINGEvaluation of Three Tests to Assess Social Cognition in Huntington Disease
RECRUITINGSafety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease
ACTIVE NOT RECRUITINGIMarkHD: in Vivo Longitudinal Imaging of HD Pathology
RECRUITINGExternal Resources
Links to major genomics databases and tools