Mutagenetix > Incidental Mutations

Incidental Mutation 'R3125:Htt'

264227

Institutional Source

Beutler Lab

Gene Symbol

Htt

Ensembl Gene

ENSMUSG00000029104

Gene Name

huntingtin

Synonyms

HD, Hdh, htt, huntingtin, IT15

MMRRC Submission

040598-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R3125 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

34761740-34912534 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 34804531 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 287 (S287P)

Ref Sequence

ENSEMBL: ENSMUSP00000078945 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000080036]

Predicted Effect

probably benign
Transcript: ENSMUST00000080036
AA Change: S287P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000078945
Gene: ENSMUSG00000029104
AA Change: S287P

Domain	Start	End	E-Value	Type
low complexity region	18	65	N/A	INTRINSIC
SCOP:d1qgra_	92	370	1e-12	SMART
low complexity region	371	388	N/A	INTRINSIC
low complexity region	432	453	N/A	INTRINSIC
low complexity region	1150	1161	N/A	INTRINSIC
low complexity region	1423	1441	N/A	INTRINSIC
Pfam:DUF3652	1494	1534	9.3e-20	PFAM
low complexity region	1812	1822	N/A	INTRINSIC
Blast:GAF	1866	2040	1e-104	BLAST
low complexity region	2461	2472	N/A	INTRINSIC
low complexity region	2611	2621	N/A	INTRINSIC
low complexity region	2622	2635	N/A	INTRINSIC
low complexity region	2857	2872	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123755

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148953

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000156490

Meta Mutation Damage Score

0.0847

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.2%

Validation Efficiency

100% (48/48)

MGI Phenotype

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

Total: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Alox5	A	T	6: 116,427,137		probably null	Het
Atp4a	G	A	7: 30,720,225	R671Q	probably benign	Het
Bag4	C	T	8: 25,769,488	A228T	probably benign	Het
Cep135	T	C	5: 76,621,363		probably null	Het
Cfap206	T	A	4: 34,716,310	H385L	possibly damaging	Het
Dach2	T	C	X: 113,819,967	I417T	possibly damaging	Het
Dhx32	T	C	7: 133,725,356	Y332C	probably damaging	Het
Dlx1	T	A	2: 71,532,396	W216R	probably damaging	Het
Dna2	G	A	10: 62,949,202	A33T	possibly damaging	Het
Doxl2	A	T	6: 48,975,371	I77F	probably damaging	Het
Dyrk1a	G	A	16: 94,668,801		probably benign	Het
Fam227b	T	C	2: 126,124,086	T140A	probably benign	Het
Fem1b	T	C	9: 62,796,554	I475V	probably benign	Het
Fign	T	A	2: 63,978,700	Q742L	possibly damaging	Het
Hip1r	A	G	5: 124,000,141	D766G	probably benign	Het
Hsd17b12	C	T	2: 94,033,958	R268Q	probably benign	Het
Icam5	A	G	9: 21,036,658	I617M	probably benign	Het
Ifi27l2b	T	C	12: 103,451,335	T198A	unknown	Het
Ip6k3	T	C	17: 27,157,542	Y65C	probably damaging	Het
Kif15	A	C	9: 122,987,961	Q542P	probably damaging	Het
Kit	G	T	5: 75,647,827	A744S	probably benign	Het
Kit	C	T	5: 75,647,828	A744V	probably null	Het
Lonp1	A	G	17: 56,626,488	I129T	possibly damaging	Het
Ltbp4	C	T	7: 27,327,778	R389Q	possibly damaging	Het
Map3k21	A	T	8: 125,941,854	K726N	probably benign	Het
Mcpt8	A	T	14: 56,083,941	I22K	probably damaging	Het
Npb	G	A	11: 120,608,902	V103I	possibly damaging	Het
Olfr131	G	A	17: 38,082,012		probably null	Het
Olfr535	T	C	7: 140,492,851	M71T	probably benign	Het
Pet2	A	T	X: 89,404,721	Y601N	probably benign	Het
Plin2	G	T	4: 86,657,144	Y389*	probably null	Het
Pnpla6	G	T	8: 3,534,670	G763C	probably null	Het
Pnpla7	A	G	2: 25,042,138	D935G	probably damaging	Het
Prr29	A	G	11: 106,374,885	S10G	probably benign	Het
Pthlh	A	T	6: 147,263,291	V27E	probably damaging	Het
Robo4	CGG	CG	9: 37,411,490		probably null	Het
Serpina12	G	A	12: 104,037,983	T130I	probably benign	Het
Slc6a18	A	G	13: 73,677,802	F43S	probably damaging	Het
Stx6	C	T	1: 155,158,908	P6S	probably damaging	Het
Togaram1	G	T	12: 64,966,344	R123L	probably damaging	Het
Trappc9	G	A	15: 73,025,967	R377W	probably damaging	Het
Trim9	C	T	12: 70,248,393	G648R	probably damaging	Het
Trpm2	T	A	10: 77,911,374	N1430I	probably damaging	Het
Trpm6	C	G	19: 18,854,431	H1553Q	probably benign	Het
Vav3	G	A	3: 109,628,168		probably null	Het
Zfp574	G	T	7: 25,081,601	A683S	possibly damaging	Het

Other mutations in Htt

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00230:Htt	APN	5	34799408	missense	probably benign	0.00
IGL00233:Htt	APN	5	34896026	splice site	probably null
IGL00559:Htt	APN	5	34849104	splice site	probably benign
IGL00765:Htt	APN	5	34877425	splice site	probably benign
IGL00950:Htt	APN	5	34891441	missense	probably benign
IGL00953:Htt	APN	5	34818677	missense	probably benign	0.04
IGL00957:Htt	APN	5	34806724	missense	probably benign
IGL01314:Htt	APN	5	34878856	missense	probably benign
IGL01412:Htt	APN	5	34898572	missense	probably damaging	0.98
IGL01510:Htt	APN	5	34907512	missense	probably damaging	1.00
IGL01617:Htt	APN	5	34876755	missense	possibly damaging	0.67
IGL01893:Htt	APN	5	34876830	missense	probably damaging	1.00
IGL01914:Htt	APN	5	34829709	missense	probably benign
IGL01994:Htt	APN	5	34832604	missense	possibly damaging	0.83
IGL02102:Htt	APN	5	34891481	splice site	probably benign
IGL02381:Htt	APN	5	34829760	missense	probably benign	0.03
IGL02529:Htt	APN	5	34819043	splice site	probably benign
IGL02678:Htt	APN	5	34899902	missense	probably damaging	1.00
IGL02707:Htt	APN	5	34829881	critical splice donor site	probably null
IGL02731:Htt	APN	5	34803793	missense	probably benign	0.41
IGL02931:Htt	APN	5	34876753	missense	probably damaging	1.00
IGL03167:Htt	APN	5	34818986	missense	probably damaging	0.98
IGL03343:Htt	APN	5	34826041	missense	probably benign
IGL03344:Htt	APN	5	34907466	missense	probably benign	0.02
IGL03344:Htt	APN	5	34879828	missense	probably benign	0.39
IGL03366:Htt	APN	5	34907580	missense	probably damaging	1.00
IGL03410:Htt	APN	5	34799445	missense	probably damaging	0.99
Chalk	UTSW	5	34907086	missense	possibly damaging	0.86
IGL02796:Htt	UTSW	5	34877482	missense	probably benign	0.43
PIT4377001:Htt	UTSW	5	34875965	missense	probably benign	0.10
R0013:Htt	UTSW	5	34820104	missense	probably benign	0.25
R0049:Htt	UTSW	5	34908662	missense	probably damaging	0.97
R0049:Htt	UTSW	5	34908662	missense	probably damaging	0.97
R0056:Htt	UTSW	5	34826078	splice site	probably benign
R0207:Htt	UTSW	5	34896908	missense	probably benign	0.11
R0329:Htt	UTSW	5	34817134	splice site	probably benign
R0494:Htt	UTSW	5	34821844	missense	possibly damaging	0.73
R0548:Htt	UTSW	5	34870746	missense	probably damaging	1.00
R0601:Htt	UTSW	5	34846003	missense	probably benign	0.08
R0799:Htt	UTSW	5	34817753	missense	probably benign	0.00
R0947:Htt	UTSW	5	34898924	missense	probably damaging	1.00
R1053:Htt	UTSW	5	34851217	critical splice acceptor site	probably null
R1147:Htt	UTSW	5	34851252	missense	probably damaging	0.98
R1147:Htt	UTSW	5	34851252	missense	probably damaging	0.98
R1478:Htt	UTSW	5	34803827	missense	probably damaging	0.99
R1573:Htt	UTSW	5	34864374	splice site	probably benign
R1677:Htt	UTSW	5	34828574	missense	probably damaging	1.00
R1792:Htt	UTSW	5	34907199	missense	probably damaging	1.00
R1816:Htt	UTSW	5	34803740	missense	probably benign	0.01
R1833:Htt	UTSW	5	34905748	splice site	probably benign
R1837:Htt	UTSW	5	34819023	missense	probably benign	0.00
R1846:Htt	UTSW	5	34848944	missense	probably damaging	0.98
R1875:Htt	UTSW	5	34794112	missense	probably benign	0.05
R1899:Htt	UTSW	5	34907085	missense	probably benign	0.01
R2013:Htt	UTSW	5	34852871	missense	probably damaging	0.99
R2062:Htt	UTSW	5	34825982	missense	probably benign	0.00
R2064:Htt	UTSW	5	34825982	missense	probably benign	0.00
R2067:Htt	UTSW	5	34825982	missense	probably benign	0.00
R2068:Htt	UTSW	5	34825982	missense	probably benign	0.00
R2131:Htt	UTSW	5	34877109	missense	possibly damaging	0.50
R2162:Htt	UTSW	5	34821718	missense	probably benign	0.44
R2169:Htt	UTSW	5	34877475	missense	probably benign	0.08
R2345:Htt	UTSW	5	34826004	missense	possibly damaging	0.80
R2433:Htt	UTSW	5	34907541	missense	possibly damaging	0.65
R3027:Htt	UTSW	5	34820095	missense	possibly damaging	0.85
R3123:Htt	UTSW	5	34804531	missense	probably benign
R3717:Htt	UTSW	5	34811522	splice site	probably benign
R3758:Htt	UTSW	5	34895970	missense	probably damaging	0.97
R3805:Htt	UTSW	5	34877204	splice site	probably null
R3833:Htt	UTSW	5	34821718	missense	probably benign	0.44
R4066:Htt	UTSW	5	34878847	missense	probably benign
R4272:Htt	UTSW	5	34849069	missense	possibly damaging	0.96
R4625:Htt	UTSW	5	34829785	missense	probably damaging	0.99
R4634:Htt	UTSW	5	34875948	missense	probably benign	0.06
R4655:Htt	UTSW	5	34906132	missense	probably benign	0.06
R4679:Htt	UTSW	5	34820080	missense	probably benign
R4684:Htt	UTSW	5	34852765	missense	probably damaging	1.00
R4832:Htt	UTSW	5	34824840	missense	probably benign	0.01
R4833:Htt	UTSW	5	34852225	missense	probably damaging	0.98
R4973:Htt	UTSW	5	34813023	missense	probably damaging	0.99
R5095:Htt	UTSW	5	34824395	missense	possibly damaging	0.89
R5132:Htt	UTSW	5	34905679	missense	possibly damaging	0.89
R5351:Htt	UTSW	5	34803833	missense	probably damaging	0.99
R5361:Htt	UTSW	5	34907584	missense	possibly damaging	0.47
R5399:Htt	UTSW	5	34877151	missense	probably damaging	0.98
R5462:Htt	UTSW	5	34885507	nonsense	probably null
R5552:Htt	UTSW	5	34821774	missense	probably benign
R5566:Htt	UTSW	5	34849075	missense	probably damaging	1.00
R5595:Htt	UTSW	5	34905397	missense	probably damaging	0.96
R5617:Htt	UTSW	5	34870806	missense	possibly damaging	0.77
R5835:Htt	UTSW	5	34813190	missense	probably benign	0.16
R5891:Htt	UTSW	5	34870823	missense	possibly damaging	0.62
R6158:Htt	UTSW	5	34907086	missense	possibly damaging	0.86
R6159:Htt	UTSW	5	34804676	missense	probably benign	0.08
R6169:Htt	UTSW	5	34907473	missense	probably damaging	1.00
R6242:Htt	UTSW	5	34846012	missense	probably damaging	1.00
R6274:Htt	UTSW	5	34852087	missense	possibly damaging	0.81
R6280:Htt	UTSW	5	34870759	missense	probably benign	0.00
R6294:Htt	UTSW	5	34821826	missense	probably benign
R6331:Htt	UTSW	5	34895887	missense	possibly damaging	0.89
R6448:Htt	UTSW	5	34875992	missense	probably benign	0.05
R6474:Htt	UTSW	5	34824895	missense	probably benign	0.06
R6592:Htt	UTSW	5	34877044	missense	possibly damaging	0.92
R6818:Htt	UTSW	5	34782767	missense	probably damaging	0.99
R6830:Htt	UTSW	5	34834326	missense	possibly damaging	0.82
R6920:Htt	UTSW	5	34877100	missense	probably null	1.00
R6962:Htt	UTSW	5	34899771	critical splice acceptor site	probably null
R7057:Htt	UTSW	5	34821723	missense	probably null	0.05
R7144:Htt	UTSW	5	34846006	missense	probably damaging	1.00
R7166:Htt	UTSW	5	34852894	missense	probably benign	0.42
R7329:Htt	UTSW	5	34829755	missense	probably benign	0.03
R7378:Htt	UTSW	5	34803799	missense	probably benign	0.04
R7418:Htt	UTSW	5	34790353	missense	possibly damaging	0.55
R7495:Htt	UTSW	5	34811477	missense	probably benign	0.00
R7554:Htt	UTSW	5	34864740	missense	probably damaging	0.97
R7575:Htt	UTSW	5	34905643	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATCTGAGTGTGCACAGCCTG -3'
(R):5'- GCGGAAAGATGCTACTTCTTTC -3'

Sequencing Primer
(F):5'- ACAGCCTGTGTTTCTCAGTC -3'
(R):5'- GGAAAGATGCTACTTCTTTCATGTCC -3'

Posted On

2015-02-05