HD HTT

Disease ID
HD
Gene ID
HTT
Updated
Feb 5, 2025
v2.2.1

Disease

Name
Huntington disease
Inheritance
Autosomal dominant
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
6.5-15/100,0002 . 9.71-17:100,000 (European) vs. 0.1-2/100,000 (African), as many as 1 in 400 have reduced penetrance (0.2-2% for 36-38 CAG) HTT alleles3 . Found across ethnicities/ancestries, with population-dependent prevalence3 .
Age of Onset(Typical)Years1  8535  44
Age of Onset Details
Typical: 35-443 ; Range: 1-854,5 .

Locus

Details
27-35 motifs are unstable/premutations, while 36-39 motifs are associated with reduced penetrance and mild phenotypes6 . >60 motifs assocated with onset age <20 years3 . Only CAG expansions are considered pathogenic, but interruptions impact pathogenicity (e.g. CAA)7 . Only fathers with premutations are considered at risk of transmitting pathogenic alleles8 . CAG repeats in the non-HD range (>= 21 repeats) may modulate psychiatric disease risk in an age-dependent manner6
Mechanism
GoF/LoF
While the primary pathogenic mechanism is gain of function of the protein product, pathogenesis is complex and multifactorial9 .
Year
199310
Location in Gene
Exon 1
Gene Strand

Alleles

Ref. Motif
CAG
Pathogenic (ref.)
CAG
Pathogenic (gene)
AGC
BenignIntermediatePathogenicUnits6  2627  3940  250

gnomAD

References

Direct supporting references for info on this page.

1
Ontology Lookup Service (OLS)
mondo:0007739
2
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:29100084
3
Huntington Disease
Nicholas S.,Caron, Galen EB,Wright, Michael R.,Hayden
GeneReviews® · 1993-01-01
genereviews:NBK1305
4
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:39441074
5
Huntington's disease: a clinical review.
Raymund A C,Roos
Orphanet journal of rare diseases · 2010-12-20
pmid:21171977
6
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:39572770
7
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:35245110
8
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:19507258
9
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:27940602
10
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:8458085

Additional 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)