Mutagenetix > Incidental Mutation

Incidental Mutation 'R6818:Htt'

537420

Institutional Source

Beutler Lab

Gene Symbol

Htt

Ensembl Gene

ENSMUSG00000029104

Gene Name

huntingtin

Synonyms

HD, Hdh, htt, huntingtin, IT15

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6818 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

34761740-34912534 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 34782767 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 77 (K77E)

Ref Sequence

ENSEMBL: ENSMUSP00000078945 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000080036
AA Change: K77E

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000078945
Gene: ENSMUSG00000029104
AA Change: K77E

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

97% (59/61)

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb5	T	A	12: 118,901,354		probably null	Het
Acot4	A	C	12: 84,042,009	E210D	probably damaging	Het
Adamts9	A	C	6: 92,905,191	S476A	probably damaging	Het
Ak1	T	A	2: 32,630,373	M61K	probably damaging	Het
Ambp	G	T	4: 63,154,006	S17*	probably null	Het
Anxa6	T	A	11: 54,979,500	M662L	probably benign	Het
Atp11b	T	C	3: 35,814,180	I467T	possibly damaging	Het
B3gat1	G	T	9: 26,751,702		probably benign	Het
Bccip	T	G	7: 133,717,759	I193S	probably damaging	Het
Ccdc170	A	G	10: 4,541,782	E401G	probably damaging	Het
Cldn16	A	G	16: 26,477,507	T78A	probably damaging	Het
Cldn24	G	T	8: 47,822,722	A194S	probably benign	Het
Cltc	A	G	11: 86,704,228	V1348A	possibly damaging	Het
Clvs1	T	C	4: 9,282,014		probably null	Het
Csmd1	C	T	8: 16,185,327	D1161N	probably damaging	Het
Cuzd1	A	G	7: 131,316,665	V181A	probably damaging	Het
Dhx30	A	G	9: 110,088,031	I435T	probably damaging	Het
Dip2b	T	C	15: 100,193,954	V858A	probably benign	Het
Dnmt3b	C	T	2: 153,686,284	T822M	probably damaging	Het
Dock10	A	T	1: 80,615,365	F97I	possibly damaging	Het
Dock8	T	C	19: 25,169,501		probably null	Het
Dvl2	T	C	11: 70,009,273	L631P	probably damaging	Het
Faf2	T	A	13: 54,641,606		probably null	Het
Fat2	T	A	11: 55,309,341	H969L	probably benign	Het
Fsip2	T	A	2: 82,985,200	V3759E	probably benign	Het
Gm10037	A	G	13: 67,833,867	Q66R	possibly damaging	Het
Gm10985	A	C	3: 53,845,253	Y19S	probably damaging	Het
Gm973	T	C	1: 59,630,169	L793P	probably damaging	Het
Gm996	C	CTCTA	2: 25,579,721		probably null	Het
H2-M1	A	G	17: 36,670,435	I236T	probably damaging	Het
Hif1a	A	T	12: 73,945,563	R765*	probably null	Het
Ift172	G	T	5: 31,265,960	Q826K	probably benign	Het
Inafm1	C	T	7: 16,273,161	A44T	probably damaging	Het
Kctd4	A	G	14: 75,963,308	T240A	probably damaging	Het
Klk1	A	T	7: 44,229,459	I124F	probably damaging	Het
Kremen1	T	C	11: 5,195,051	T442A	probably benign	Het
Mei4	T	A	9: 82,025,521	D202E	probably benign	Het
Mest	T	A	6: 30,746,287	D284E	probably damaging	Het
Nsfl1c	T	A	2: 151,503,020	Y95*	probably null	Het
Olfr121	T	A	17: 37,752,424	V190D	possibly damaging	Het
Olfr1282	T	G	2: 111,335,314	I255L	probably benign	Het
Olfr1349	T	C	7: 6,514,551	M293V	probably damaging	Het
Olfr316	T	A	11: 58,757,957	C97*	probably null	Het
Pgm2	T	A	4: 99,963,566	I220N	probably damaging	Het
Pirt	T	A	11: 66,925,893	V10E	possibly damaging	Het
Prl7d1	C	A	13: 27,714,471	M19I	probably benign	Het
Samhd1	T	C	2: 157,107,497	N490D	probably benign	Het
Scn2a	C	A	2: 65,688,669	S413*	probably null	Het
Serpinb6e	A	T	13: 33,832,354		probably null	Het
Slitrk5	A	G	14: 111,680,294	D450G	probably benign	Het
Tchh	A	G	3: 93,443,411	T53A	probably damaging	Het
Tmem44	A	T	16: 30,543,221		probably null	Het
Tpm3-rs7	A	G	14: 113,315,016	E114G	possibly damaging	Het
Treml2	A	G	17: 48,302,897	Y119C	probably damaging	Het
Ubxn1	T	A	19: 8,873,881		probably null	Het
Vmn2r84	A	T	10: 130,386,278	M691K	probably benign	Het
Vmn2r97	A	T	17: 18,947,931	I816F	possibly damaging	Het
Was	GCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTC	GCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTC	X: 8,086,211		probably benign	Het
Wfdc2	T	C	2: 164,563,150		probably null	Het
Zscan4-ps3	T	C	7: 11,613,059	S341P	probably 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
R3125: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
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
R7763:Htt	UTSW	5	34852190	missense	probably damaging	1.00
R7782:Htt	UTSW	5	34882992	missense	probably benign	0.03
R7850:Htt	UTSW	5	34852287	splice site	probably null
R7870:Htt	UTSW	5	34898547	missense	possibly damaging	0.77
R7871:Htt	UTSW	5	34864649	missense	probably benign	0.00
R7879:Htt	UTSW	5	34823908	missense	probably benign
R7992:Htt	UTSW	5	34829881	critical splice donor site	probably null
R8058:Htt	UTSW	5	34820100	missense	probably benign
R8168:Htt	UTSW	5	34882956	missense	probably benign	0.00
R8188:Htt	UTSW	5	34761943	missense	probably benign	0.03
R8262:Htt	UTSW	5	34895960	missense	probably benign
R8343:Htt	UTSW	5	34905724	missense	probably damaging	1.00
R8353:Htt	UTSW	5	34877155	missense	possibly damaging	0.49
R8769:Htt	UTSW	5	34820289	missense	probably benign	0.05
R8808:Htt	UTSW	5	34889447	missense	probably benign	0.10
R8825:Htt	UTSW	5	34825960	missense	probably benign	0.24
R8843:Htt	UTSW	5	34889465	missense	possibly damaging	0.92
R8856:Htt	UTSW	5	34903331	missense	probably benign	0.44
R8882:Htt	UTSW	5	34821717	missense	probably benign
R8898:Htt	UTSW	5	34819032	missense	probably benign	0.01
R8964:Htt	UTSW	5	34905376	missense	probably benign	0.09
R8987:Htt	UTSW	5	34820024	missense	probably benign	0.18
R8991:Htt	UTSW	5	34905718	missense	probably damaging	1.00
R9005:Htt	UTSW	5	34817751	missense	possibly damaging	0.92
R9019:Htt	UTSW	5	34866576	missense	probably damaging	1.00
R9057:Htt	UTSW	5	34852110	missense	possibly damaging	0.86
R9157:Htt	UTSW	5	34829827	missense	probably null	0.89
R9205:Htt	UTSW	5	34819023	missense	probably benign	0.00
R9223:Htt	UTSW	5	34905348	missense	probably benign	0.01
R9243:Htt	UTSW	5	34898932	splice site	probably benign
R9329:Htt	UTSW	5	34832613	missense	possibly damaging	0.69
R9355:Htt	UTSW	5	34895903	missense	probably benign
R9402:Htt	UTSW	5	34848980	missense	probably damaging	1.00
R9446:Htt	UTSW	5	34761928	missense	probably benign
R9716:Htt	UTSW	5	34854675	missense	probably damaging	1.00
Z1177:Htt	UTSW	5	34852231	missense	probably null	0.87

Predicted Primers

PCR Primer
(F):5'- AGTGTCGTGTGAGGAAGCTC -3'
(R):5'- GGTTACAGGTATATCCACCACCAC -3'

Sequencing Primer
(F):5'- GGAAGCTCTTAGTAGACCTCATCTG -3'
(R):5'- AGATGGCTCAGCACTGGC -3'

Posted On

2018-10-18