HTT Gene

HGNC Family	Endogenous ligands
Name	huntingtin
Description	Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range of trinucleotide repeats (9-35) has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Huntingtin (HTT) is a multifunctional protein critical for neuronal integrity. Wild‐type HTT facilitates several essential cellular processes, including the transport of neurotrophic factors such as brain‐derived neurotrophic factor along microtubules (for example, via huntingtin‐associated protein 1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and fast axonal trafficking through its interactions with motor protein complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, HTT modulates gene expression by interacting with transcription factors and coactivators such as Sp1 and TAFII130, thereby influencing the transcription of genes including those for dopamine receptors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, HTT is implicated in intracellular Ca²⁺ homeostasis through a ternary complex with HAP1A and the inositol 1,4,5‐trisphosphate receptor (InsP₃R1)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, mutant forms of HTT bearing expanded polyglutamine tracts lose these protective functions and acquire toxic properties. Aberrant proteolytic processing—most notably caspase‐6‐mediated cleavage—has been shown to be a key event in neurodegeneration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while mutant HTT is also generated by aberrant splicing of exon 1, producing highly pathogenic protein fragments."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " These mutant species impair mitochondrial function by, for example, inducing mitochondrial permeability transition"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and by perturbing the normal fission–fusion balance, which culminates in energy deficits. In addition, disruption of neuroprotective pathways is evident; activation of the insulin‐like growth factor–Akt pathway normally promotes HTT phosphorylation and neuronal survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, mutant HTT exerts non–cell‐autonomous toxicity. Its accumulation in glial cells reduces the expression of glutamate transporters, thereby impairing glutamate uptake and exacerbating excitotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, differential activation of synaptic versus extrasynaptic NMDA receptors can modulate HTT inclusion formation and neuronal survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, high‐throughput approaches have revealed that HTT interacts with a diverse network of proteins—including components involved in synaptic transmission, cytoskeletal organization, and vesicular trafficking—highlighting its broad role in neuronal physiology and how disruption of these interactions may contribute to Huntington’s disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that while wild‐type HTT is essential for neuronal survival through roles in intracellular transport, transcription regulation, and Ca²⁺ signaling, mutant HTT subverts these processes by misprocessing, mislocalization, and harmful aggregation, thereby driving the selective neurodegeneration seen in Huntington’s disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laurent R Gauthier, Bénédicte C Charrin, Maria Borrell-Pagès, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2004.06.018"}], "href": "https://doi.org/10.1016/j.cell.2004.06.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15242649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15242649"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eugenia Trushina, Roy B Dyer, John D Badger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.18.8195-8209.2004"}], "href": "https://doi.org/10.1128/MCB.24.18.8195-8209.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15340079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15340079"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anthone W Dunah, Hyunkyung Jeong, April Griffin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1072613"}], "href": "https://doi.org/10.1126/science.1072613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11988536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11988536"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tie-Shan Tang, Huiping Tu, Edmond Y W Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(03)00366-0"}], "href": "https://doi.org/10.1016/s0896-6273(03"}, {"type": "t", "text": "00366-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12873381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12873381"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rona K Graham, Yu Deng, Elizabeth J Slow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.04.026"}], "href": "https://doi.org/10.1016/j.cell.2006.04.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16777606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16777606"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kirupa Sathasivam, Andreas Neueder, Theresa A Gipson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1221891110"}], "href": "https://doi.org/10.1073/pnas.1221891110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23341618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23341618"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ashwani K Thakur, Murali Jayaraman, Rakesh Mishra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1570"}], "href": "https://doi.org/10.1038/nsmb.1570"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19270701"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19270701"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yeun Su Choo, Gail V W Johnson, Marcy MacDonald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh162"}], "href": "https://doi.org/10.1093/hmg/ddh162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15163634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15163634"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sandrine Humbert, Elzbieta A Bryson, Fabrice P Cordelières, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1534-5807(02)00188-0"}], "href": "https://doi.org/10.1016/s1534-5807(02"}, {"type": "t", "text": "00188-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12062094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12062094"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ji-Yeon Shin, Zhi-Hui Fang, Zhao-Xue Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200508072"}], "href": "https://doi.org/10.1083/jcb.200508072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16365166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16365166"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shu-ichi Okamoto, Mahmoud A Pouladi, Maria Talantova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2056"}], "href": "https://doi.org/10.1038/nm.2056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19915593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19915593"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Linda S Kaltenbach, Eliana Romero, Robert R Becklin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Huntingtin interacting proteins are genetic modifiers of neurodegeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.0030082"}], "href": "https://doi.org/10.1371/journal.pgen.0030082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17500595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17500595"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Stephen Willingham, Tiago Fleming Outeiro, Michael J DeVit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1090389"}], "href": "https://doi.org/10.1126/science.1090389"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14657499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14657499"}]}]}]}
Synonyms	HD, IT15, LOMARS
Proteins	HD_HUMAN
NCBI Gene ID	3064
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HTT has 9,420 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 118 datasets.

Click the + buttons to view associations for HTT from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HTT Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by HTT gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HTT gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of HTT gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of HTT gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of HTT gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HTT gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving HTT protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HTT gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HTT gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HTT gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HTT gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of HTT gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HTT protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HTT gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HTT gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of HTT gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HTT gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HTT protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HTT protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CORUM Protein Complexes	protein complexs containing HTT protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HTT gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HTT gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HTT gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HTT gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HTT gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HTT protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HTT gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HTT gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HTT gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HTT gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HTT gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with HTT gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with HTT gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HTT gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HTT gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HTT gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HTT gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing HTT from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HTT gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HTT gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.