HTT huntingtin [Homo sapiens (human)] - Gene

Summary

Official Symbol: HTTprovided by HGNC
Official Full Name: huntingtinprovided by HGNC
Primary source: HGNC:HGNC:4851
See related: Ensembl:ENSG00000197386 MIM:613004; AllianceGenome:HGNC:4851
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HD; IT15; LOMARS
Summary: 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]
Expression: Ubiquitous expression in brain (RPKM 9.1), skin (RPKM 8.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p16.3

Exon count:: 67

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (3074681..3243960)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (3073408..3242718)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (3076408..3245687)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Nucleation of Huntingtin Aggregation Proceeds via Conformational Conversion of Pre-Formed, Sparsely-Populated Tetramers.
Title: Nucleation of Huntingtin Aggregation Proceeds via Conformational Conversion of Pre-Formed, Sparsely-Populated Tetramers.
Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure.
Title: Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure.
Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights.
Title: Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights.
Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype.
Title: Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype.
Evidence of mutant huntingtin and tau-related pathology within neuronal grafts in Huntington's disease cases.
Title: Evidence of mutant huntingtin and tau-related pathology within neuronal grafts in Huntington's disease cases.
Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions.
Title: Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions.
Huntingtin HTT1a is generated in a CAG repeat-length-dependent manner in human tissues.
Title: Huntingtin HTT1a is generated in a CAG repeat-length-dependent manner in human tissues.
Cell-type-specific CAG repeat expansions and toxicity of mutant Huntingtin in human striatum and cerebellum.
Title: Cell-type-specific CAG repeat expansions and toxicity of mutant Huntingtin in human striatum and cerebellum.
A mother and her daughter carrying a pathogenic expansion of the HTT gene with a phenotype encompassing motor neuron disease and Huntington's disease.
Title: A mother and her daughter carrying a pathogenic expansion of the HTT gene with a phenotype encompassing motor neuron disease and Huntington's disease.
Interaction between huntingtin exon 1 and HEAT repeat structure probed by chimeric model proteins.
Title: Interaction between huntingtin exon 1 and HEAT repeat structure probed by chimeric model proteins.

Submit: New GeneRIF Correction See all GeneRIFs (576)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Huntington disease MedGen: C0020179 OMIM: 143100 GeneReviews: Huntington Disease	not available
Lopes-Maciel-Rodan syndrome MedGen: C4479491 OMIM: 617435 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
capsid	gag	The interaction of HIV-1 CA with human cellular huntingtin protein (HTT) is identified by yeast two-hybrid screen	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-59533 (e-PCR)
- UniSTS:34063

D4S2663 (e-PCR)
- UniSTS:31249

G33683 (e-PCR)
- UniSTS:8980

G42605 (e-PCR)
- UniSTS:94507

PMC20760P1 (e-PCR)
- UniSTS:271970

GDB:363582 (e-PCR)
- UniSTS:156775

GDB:363587 (e-PCR)
- UniSTS:156776

GDB:197987 (e-PCR)
- UniSTS:156011

SHGC-30823 (e-PCR)
- UniSTS:70263

GDB:249651 (e-PCR)
- UniSTS:156286

SHGC-50176 (e-PCR)
- UniSTS:37272

GDB:316174 (e-PCR)
- UniSTS:156570

D4S1337 (e-PCR)
- UniSTS:85926

SHGC-51023 (e-PCR)
- UniSTS:22694

RH66772 (e-PCR)
- UniSTS:17834

D4S281 (e-PCR)
- UniSTS:54734

SHGC-67369 (e-PCR)
- UniSTS:39383

GDB:372940 (e-PCR)
- UniSTS:156892

WI-20376 (e-PCR)
- UniSTS:42205

SHGC-67859 (e-PCR)
- UniSTS:43486

PMC166399P1 (e-PCR)
- UniSTS:271586

PMC166399P2 (e-PCR)
- UniSTS:271587

D4S3290 (e-PCR)
- UniSTS:36579

HD__6704 (e-PCR)
- UniSTS:468456

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables beta-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
enables dynactin binding	IPI Inferred from Physical Interaction more info	PubMed
enables dynein intermediate chain binding	IDA Inferred from Direct Assay more info	PubMed
enables heat shock protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables p53 binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphoprotein phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables profilin binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Golgi organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in establishment of mitotic spindle orientation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microtubule-based transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of aggrephagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of lipophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mitophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of CAMKK-AMPK signaling cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cAMP-dependent protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vesicle transport along microtubule	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vocal learning	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in autophagosome	IDA Inferred from Direct Assay more info	PubMed
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in centriole	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytoplasmic vesicle membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in inclusion body	IMP Inferred from Mutant Phenotype more info	PubMed
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
located_in perinuclear region of cytoplasm	IMP Inferred from Mutant Phenotype more info	PubMed
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic cytosol	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: huntingtin

Names: huntington disease protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009378.1 RefSeqGene

Range

5001..174286

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_763

mRNA and Protein(s)

NM_001388492.1 → NP_001375421.1 huntingtin isoform 1

Status: REVIEWED

Source sequence(s)

AL390059

Consensus CDS

CCDS43206.1

UniProtKB/Swiss-Prot

P42858, Q9UQB7

UniProtKB/TrEMBL

A0A7P0TA78

Related

ENSP00000347184.5, ENST00000355072.11

Conserved Domains (2) summary

sd00044
Location:131 → 153

HEAT; HEAT repeat [structural motif]

pfam12372
Location:1513 → 1553

DUF3652; Huntingtin protein region
NM_002111.8 → NP_002102.4 huntingtin isoform 2

See identical proteins and their annotated locations for NP_002102.4

Status: REVIEWED

Source sequence(s)

AL390059, BM661887, L12392

UniProtKB/TrEMBL

A0A7P0TA78

Conserved Domains (2) summary

pfam12372
Location:1527 → 1553

DUF3652; Huntingtin protein region

sd00044
Location:133 → 155

HEAT; HEAT repeat [structural motif]