Locus HD HTT
Disease ID
HD
Gene ID
HTT
Updated
Jun 15, 2026
v2.22.0
v2.22.0
Other gene loci
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Clinical Links
Bioinformatical Links
Disease
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Name Huntington disease
Inheritance
Description Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia1 .
Prevalence
1 10,000
HPO Terms
–
Association
MendelianRisk
Locus
hg19 chr4:3076603-3076660
hg38 chr4:3074876-3074933
Details 27-35 motifs are unstable/premutations, while 36-39 motifs are associated with reduced penetrance and mild phenotypes6 , and alleles over 40 repeats are typically fully penetrant3 . >60 motifs associated with onset age <20 years3 . Only CAG expansions are considered pathogenic, but interruptions impact pathogenicity (CAA)7,8 . Only fathers with premutations are considered at risk of transmitting pathogenic alleles9 . CAG repeat size 21-35 may continuously modulate brain structure and psychiatric disease risk in an age-dependent manner6 10 . Somatic expansion of HTT CAG repeats in vulnerable tissues is proposed to contribute to age-dependent onset and neurodegeneration, with greater repeat instability associated with earlier disease onset11,12 . Undiagnosed carriers of premutation and pathogenic HTT expansions, exhibit reduced striatal brain volumes and elevated neurofilament light chain levels before clinical diagnosis, consistent with findings observed across other loci13 .
Mechanism While the primary pathogenic mechanism is gain of function of the protein product, pathogenesis is complex and multifactorial14 . Reduced SCN4B expression in striatal neurons has been implicated as a modifier of HD-associated phenotype severity, potentially contributing to dysfunction in motor associated striatal neuronal populations15 .
GoF/LoF
Detection
PCR methods have reliably detected expansions up to ~115 repeats, but very large expansions may require Southern blotting [@genereviews:NBK1305]. Long-read sequencing has resolved interruptions and validated sizing [@pmid:41512049].
Alleles
Ref. Motif Reference motif, reference orientation
CAG
Ranges
Benign (ref.) Benign motif, reference orientation
–
Benign (gene) Benign motif, gene orientation
–
Pathogenic (ref.) Pathogenic motif, reference orientation
CAG
Pathogenic (gene) Pathogenic motif, gene orientation
AGC
Unknown (ref.) Unknown motif, reference orientation
–
Unknown (gene) Unknown motif, gene orientation
–
Interruption (ref.) Interruption motif, reference orientation
CAA
Interruption (gene) Interruption motif, gene orientation
AAC
gnomAD
References
Direct supporting references for info on this page.
1
Ontology Lookup Service (OLS)
mondo:00077392
Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.
Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti
American journal of human genetics · 2017-11-02
pmid:291000844
Expanding the Phenotype of Extremely Early Onset Juvenile Huntington's Disease: A Case Report and Review of Previously Published Cases.
Zöe,Powis, Jonathon,Lutz, Khalida,Liaquat, Jyes A,Querubin, Sat Dev,Batish
American journal of medical genetics. Part A · 2024-10-23
pmid:394410745
Huntington's disease: a clinical review.
Raymund A C,Roos
Orphanet journal of rare diseases · 2010-12-20
pmid:211719776
Huntingtin CAG repeat size variations below the Huntington's disease threshold: associations with depression, anxiety and basal ganglia structure.
Magdalena,Vater, Nicolas,Rost, Gertrud,Eckstein, Susann,Sauer, Alina,Tontsch, Angelika,Erhardt, Susanne,Lucae, Tanja,Brückl, Thomas,Klopstock, Philipp G,Sämann, Elisabeth B,Binder
European journal of human genetics : EJHG · 2024-11-21
pmid:395727707
Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.
Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson
Science advances · 2022-03-04
pmid:352451108
When repetita no-longer iuvant: somatic instability of the CAG triplet in Huntington's disease.
Elena,Cattaneo, Davide,Scalzo, Martina,Zobel, Raffaele,Iennaco, Camilla,Maffezzini, Dario,Besusso, Simone,Maestri
Nucleic acids research · 2025-01-07
pmid:396737939
Estimating the probability of de novo HD cases from transmissions of expanded penetrant CAG alleles in the Huntington disease gene from male carriers of high normal alleles (27-35 CAG).
Audrey E,Hendricks, Jeanne C,Latourelle, Kathryn L,Lunetta, L Adrienne,Cupples, Vanessa,Wheeler, Marcy E,MacDonald, James F,Gusella, Richard H,Myers
American journal of medical genetics. Part A · 2009-07-01
pmid:1950725810
Huntingtin CAG repeat is a continuous modifier of brain structure and health vulnerability
Harriet,Cullen, Christopher,Clarkson, Henrique,Nascimento, Matteo,Zanovello, Jeffrey,Long, Mark,Caulfield, Michael,Simpson, Sarah J,Tabrizi, Arianna,Tucci
Genetic and Genomic Medicine · 2026-05-12
doi:https://doi.org/10.64898/2026.05.08.2635222311
Extensive transcriptomic changes in cellular and animal models of Huntington's disease depending on the length of CAG repeats in the exon 1 of the HTT gene.
Aneta,Szulc, Beata M,Walter, Lidia,Gaffke, Karolina,Wiśniewska, Magdalena,Żabińska, Estera,Rintz, Zuzanna,Cyske, Michał,Grabski, Oleksandr,Pankiv, Magdalena,Podlacha, Karolina,Pierzynowska, Grzegorz,Węgrzyn
Biochemical and biophysical research communications · 2026-04-01
pmid:4192679312
Long somatic DNA-repeat expansion drives neurodegeneration in Huntington's disease.
Robert E,Handsaker, Seva,Kashin, Nora M,Reed, Steven,Tan, Won-Seok,Lee, Tara M,McDonald, Kiely,Morris, Nolan,Kamitaki, Christopher D,Mullally, Neda R,Morakabati, Melissa,Goldman, Gabriel,Lind, Rhea,Kohli, Elisabeth,Lawton, Marina,Hogan, Kiku,Ichihara, Sabina,Berretta, Steven A,McCarroll
Cell · 2025-01-16
pmid:3982418213
Population-scale repeat expansions elucidate disease risk and brain atrophy.
Vijay Kumar,Pounraja, Jae Hoon,Sul, Joseph,Herman, Sean,O'Keeffe, Veera,Rajagopal, Xiaodong,Bai, Michael D,Kessler, Neelroop,Parikshak, Karl,Landheer, Xingmin,Zhang, Sean,Yu, Lance,Zhang, Michelle G,LeBlanc, Jennifer,Rico-Varela, Frederic,Grau, Sarah,Wolf, Sriramkumar,Sundaramoorthy, Farshid,Sepehrband, Eli A,Stahl, Yuda,Huo, Mohsin,Ahmed, Susan,Croll, William,Salerno, John D,Overton, Jonathan,Marchini, Jeffrey,Reid, Luca A,Lotta, Aris,Baras, Goncalo R,Abecasis, Giovanni,Coppola, Sahar,Gelfman
Nature · 2026-04-08
pmid:4195173314
Huntington's Disease: Mechanisms of Pathogenesis and Therapeutic Strategies.
Maria,Jimenez-Sanchez, Floriana,Licitra, Benjamin R,Underwood, David C,Rubinsztein
Cold Spring Harbor perspectives in medicine · 2017-07-05
pmid:2794060215
Scn4b Modulates Huntington's Disease Phenotype Severity in vivo.
Suphinya,Sathitloetsakun, Vanessa,Farrell, S Sebastian,Pineda, Hyeseung,Lee, Jung Hoon,Shin, Francisco J,Garcia, Raleigh M,Linville, Manolis,Kellis, Veronica A,Alvarez, Myriam,Heiman
bioRxiv : the preprint server for biology · 2026-03-10
pmid:4195936716
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Cell · 1993-03-26
pmid:8458085Additional Literature
Additional literature related to this locus.
Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem
repeats, and disease, in medline format)
Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.
Ashley B,Robbins, Paul T,Ranum, Icnelia,Huerta-Ocampo, Michael,Kuckyr, Beverly L,Davidson
Molecular neurodegeneration · 2026-05-28
pmid:42210302Clinical implications of loss of interruption variants for diagnosis, genetic counselling, and clinical trials in Huntington's disease.
Hailey,Findlay Black, Jessica,Levesley, Chris,Kay, Stephanie,Bortnick, Kyla,Javier, Michael R,Hayden
Journal of Huntington's disease · 2026-05-27
pmid:42202221Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.
Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak
International journal of molecular sciences · 2026-05-13
pmid:42196324DNA methylation profiling in Huntington's disease reveals disease associated changes in the striatum.
Gregory,Wheildon, Adam R,Smith, Luke,Weymouth, Joshua,Harvey, Morteza,Kouhsar, Lachlan F,MacBean, Claire,Troakes, Ehsan,Pishva, Rebecca G,Smith, Katie,Lunnon
Clinical epigenetics · 2026-05-26
pmid:42185880The pathological Huntingtin CAG triplet expansion differentially affects the diagnosis of systemic and organ-specific autoimmune diseases.
Moritz,Heyd, G Bernhard,Landwehrmeyer, Jan,Lewerenz
Frontiers in immunology · 2026-05-08
pmid:42183198C57BL/6 BAC-CAG Huntington's disease mice show somatic CAG expansion and responses to small interfering RNAs comparable to the FVB strain.
Jillian,Belgrad, Ashley,Summers, Samuel,Hildebrand, Ellen,Sapp, Eric,Luu, Nozomi,Yamada, Dan,O'Reilly, Thomas F,Vogt, David,Howland, X William,Yang, Marian,DiFiglia, Neil,Aronin, Anastasia,Khvorova
bioRxiv : the preprint server for biology · 2026-05-12
pmid:42182232Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.
Emily N P,Prowse, Brooke A,Turkalj, Muriel,Sébastien, Lale,Gursu, Daniel,Beaudet, Jia,Feng, Chengqian,Zhou, Heidi M,McBride, Gary J,Brouhard, Mahmoud A,Pouladi, Adam G,Hendricks
iScience · 2026-04-17
pmid:42181265Understanding Huntington's Disease: Epidemiology, Mechanisms, and Modeling Approaches.
Satya,Prakash, Neha,Kumari, Lovedeep,Singh, Kamal,Shah, Hitesh Kumar,Dewangan, Deepika,Bhatia
CNS & neurological disorders drug targets · 2026-05-11
pmid:42152675Induced pluripotent stem cells from a transgenic minipig model of Huntington's disease reveal early metabolic changes.
Irena,Rysankova, David,Sekac, Hana,Hansikova, Katerina Vodickova,Kepkova, Petr,Vodicka, Michaela,Vaskovicova, Marie,Altmanova, Stefan,Juhas, Jana,Juhasova, Eliska,Taborska, Jiri,Klempir, Jan,Motlik, Jiri,Klima, Lars,Eide, Zdenka,Ellederova
Disease models & mechanisms · 2026-05-11
pmid:42109206