HTT
Chr 4ADARhuntingtin
Also known as: HD, IT15, LOMARS
Huntingtin is a widely expressed protein required for normal development, though its precise cellular function remains incompletely understood. Mutations cause Huntington disease (typically adult-onset progressive neurodegeneration affecting movement, cognition, and behavior) and Lopes-Maciel-Rodan syndrome, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is extremely intolerant to loss-of-function variants (pLI near 1.0), indicating it is essential for normal cellular function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HTT · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Home-based Transcranial Direct Current Stimulation in Postpartum Depression: the Feasibility Study and Pilot Study
NOT YET RECRUITINGA Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease
RECRUITINGMolecular and Functional Imaging in Monogenic PD.
RECRUITINGGene Therapy Development and Validation for Huntington's Disease Fibro TG-HD
RECRUITINGContinuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants
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 RECRUITINGSerotonin Release in Premotor and Motor PD
RECRUITINGThe Signature of Alzheimer's Disease in Subjective Cognitive Decline
RECRUITINGSafety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease
ACTIVE NOT RECRUITINGA Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
RECRUITINGDevelopment of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
RECRUITINGExternal Resources
Links to major genomics databases and tools