|Institutional Source||Beutler Lab|
|Synonyms||HD, Hdh, htt, huntingtin, IT15|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R4625 (G1)|
|Chromosomal Location||34761740-34912534 bp(+) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||T to A at 34829785 bp|
|Amino Acid Change||Valine to Glutamic Acid at position 1116 (V1116E)|
|Ref Sequence||ENSEMBL: ENSMUSP00000078945 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000080036]|
|Predicted Effect||probably damaging
AA Change: V1116E
PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)
AA Change: V1116E
|Meta Mutation Damage Score||0.7193|
|Coding Region Coverage||
|Validation Efficiency||97% (75/77)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Null mutants gastrulate abnormally and die in utero. Conditional mutants are small with progressive neurodegeneration. Knock-ins of 20-150 CAG repeat units variably mimic Huntington's with late-onset motor defects, reactive gliosis and neuronal inclusions. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Htt||
(F):5'- ACTTAGGCCACAACCTCTTC -3'
(R):5'- TTCTGAGCTTCATGGCTGACATC -3'
(F):5'- TTCCCACCTAACACATTGCGG -3'
(R):5'- TGAGCTTCATGGCTGACATCAAAAC -3'