Mutagenetix > Incidental Mutation

Incidental Mutation 'R7284:Hmgcr'

565899

Institutional Source

Beutler Lab

Gene Symbol

Hmgcr

Ensembl Gene

ENSMUSG00000021670

Gene Name

3-hydroxy-3-methylglutaryl-Coenzyme A reductase

Synonyms

Red, 3-hydroxy-3-methylglutaryl-CoA reductase, HMG-CoAR

MMRRC Submission

045392-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7284 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

96785475-96807444 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 96789173 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glycine at position 716 (V716G)

Ref Sequence

ENSEMBL: ENSMUSP00000022176 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022176] [ENSMUST00000168855] [ENSMUST00000169202] [ENSMUST00000170287]

AlphaFold

Q01237

Predicted Effect

probably damaging
Transcript: ENSMUST00000022176
AA Change: V716G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: V716G

Domain	Start	End	E-Value	Type
transmembrane domain	20	37	N/A	INTRINSIC
Pfam:Patched	56	342	2.7e-11	PFAM
Pfam:Sterol-sensing	85	234	3.4e-20	PFAM
Pfam:HMG-CoA_red	490	870	2.2e-150	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000168855

Predicted Effect

SMART Domains

Protein: ENSMUSP00000132155
Gene: ENSMUSG00000021670
AA Change: V178G

Domain	Start	End	E-Value	Type
Pfam:HMG-CoA_red	35	219	8.8e-76	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000169945
AA Change: V46G

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000128642
Gene: ENSMUSG00000021670
AA Change: V46G

Domain	Start	End	E-Value	Type
Pfam:HMG-CoA_red	1	96	1.8e-37	PFAM
Pfam:HMG-CoA_red	96	148	2.8e-17	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000170287
AA Change: V716G

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: V716G

Domain	Start	End	E-Value	Type
transmembrane domain	20	37	N/A	INTRINSIC
Pfam:Patched	56	347	1.4e-11	PFAM
Pfam:Sterol-sensing	85	234	7.4e-20	PFAM
Pfam:HMG-CoA_red	488	819	1.3e-148	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.3%

Validation Efficiency

99% (77/78)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
PHENOTYPE: Inactivation of both copies of this gene results in early embryonic lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2900092C05Rik	G	T	7: 12,246,605 (GRCm39)	E34*	probably null	Het
4933421I07Rik	C	T	7: 42,097,404 (GRCm39)	R30H	probably damaging	Het
AB124611	C	A	9: 21,450,400 (GRCm39)	Q158K	probably benign	Het
Abcc3	C	T	11: 94,247,873 (GRCm39)	A1207T	probably benign	Het
Abcc9	A	T	6: 142,628,643 (GRCm39)	L367Q	probably damaging	Het
Aftph	T	C	11: 20,676,812 (GRCm39)	K266E	probably benign	Het
Akap9	T	A	5: 4,006,246 (GRCm39)	D190E	probably damaging	Het
Angel1	G	T	12: 86,767,298 (GRCm39)	D359E	probably damaging	Het
Ano6	T	C	15: 95,846,184 (GRCm39)	I474T	probably damaging	Het
Atp2c1	A	T	9: 105,398,008 (GRCm39)		probably null	Het
Best1	T	C	19: 9,963,737 (GRCm39)		probably null	Het
Bhlha9	A	G	11: 76,563,492 (GRCm39)	S40G	probably benign	Het
Cabin1	G	A	10: 75,530,668 (GRCm39)	R178C		Het
Ccnb1ip1	A	G	14: 51,029,736 (GRCm39)	Y109H	probably damaging	Het
Col14a1	T	C	15: 55,381,715 (GRCm39)	S1763P	probably damaging	Het
Dars1	T	C	1: 128,300,004 (GRCm39)	T327A	probably benign	Het
Dhx8	T	C	11: 101,645,648 (GRCm39)	Y889H	probably damaging	Het
Dlg4	T	A	11: 69,932,908 (GRCm39)	Y523*	probably null	Het
Dnah10	A	T	5: 124,909,662 (GRCm39)	D4484V	probably benign	Het
Dnah9	A	T	11: 65,881,302 (GRCm39)	M2591K	probably damaging	Het
Dock2	T	C	11: 34,180,672 (GRCm39)	E1715G	probably benign	Het
Dym	A	G	18: 75,252,242 (GRCm39)	Y336C	possibly damaging	Het
Ezh2	A	G	6: 47,521,453 (GRCm39)	M439T	probably benign	Het
Folr1	T	G	7: 101,508,677 (GRCm39)	N83H	possibly damaging	Het
Ganab	T	C	19: 8,889,904 (GRCm39)	L656P	probably damaging	Het
Gmnc	T	C	16: 26,779,542 (GRCm39)	H161R	probably benign	Het
Gria4	A	G	9: 4,472,017 (GRCm39)	Y491H	probably damaging	Het
Heatr3	T	A	8: 88,883,402 (GRCm39)	C412S	possibly damaging	Het
Igsf9	A	G	1: 172,324,479 (GRCm39)	D799G	probably damaging	Het
Ikbkb	T	C	8: 23,158,976 (GRCm39)	T501A	probably benign	Het
Kbtbd3	C	T	9: 4,330,690 (GRCm39)	R355*	probably null	Het
Kcna7	T	A	7: 45,058,652 (GRCm39)	I313N	probably damaging	Het
Kirrel1	A	C	3: 86,990,694 (GRCm39)	D709E	probably benign	Het
Klb	T	A	5: 65,540,821 (GRCm39)	S971R	probably benign	Het
Krtap4-13	A	T	11: 99,700,238 (GRCm39)	C140*	probably null	Het
Lacc1	A	T	14: 77,268,309 (GRCm39)	L334Q	probably damaging	Het
Map6d1	T	A	16: 20,059,775 (GRCm39)	R97*	probably null	Het
Mgat5b	T	C	11: 116,835,746 (GRCm39)	S129P	probably damaging	Het
Mmp1a	TG	TGG	9: 7,465,083 (GRCm38)		probably null	Het
Myh9	G	A	15: 77,671,796 (GRCm39)	R432C	probably damaging	Het
Ncf4	A	G	15: 78,144,902 (GRCm39)	T236A	probably benign	Het
Neb	T	C	2: 52,148,804 (GRCm39)	D2581G	probably damaging	Het
Nid1	T	A	13: 13,663,675 (GRCm39)	M778K	probably benign	Het
Npas2	A	G	1: 39,363,548 (GRCm39)	D209G	probably benign	Het
Nploc4	C	T	11: 120,307,196 (GRCm39)	V181I	possibly damaging	Het
Nrcam	A	T	12: 44,610,817 (GRCm39)	I506F	probably damaging	Het
Or52w1	T	A	7: 105,017,752 (GRCm39)	M73K	probably damaging	Het
Or5h27	A	G	16: 59,006,331 (GRCm39)	*172Q	probably null	Het
Or6c3b	T	C	10: 129,527,220 (GRCm39)	N230S	probably benign	Het
Pask	T	A	1: 93,248,391 (GRCm39)	Q970L	probably benign	Het
Pfkfb4	T	C	9: 108,840,308 (GRCm39)	I308T	possibly damaging	Het
Pla2g4d	A	T	2: 120,114,617 (GRCm39)	L38Q	probably damaging	Het
Pld1	A	G	3: 28,185,882 (GRCm39)	T1036A	possibly damaging	Het
Pom121l2	A	G	13: 22,166,775 (GRCm39)	T349A	probably damaging	Het
Ppp1r13b	A	G	12: 111,801,400 (GRCm39)	I551T	possibly damaging	Het
Prps1l1	A	G	12: 35,035,317 (GRCm39)	N144S	possibly damaging	Het
Prss56	A	G	1: 87,113,123 (GRCm39)	N179S	probably null	Het
Prune2	T	C	19: 17,097,250 (GRCm39)	L918P	probably damaging	Het
Ptprz1	C	T	6: 23,000,097 (GRCm39)	T729I	probably damaging	Het
Relch	T	A	1: 105,662,308 (GRCm39)	H942Q	probably benign	Het
Rrp7a	T	C	15: 83,006,071 (GRCm39)	T60A	probably damaging	Het
Snx27	A	G	3: 94,431,498 (GRCm39)	Y299H	probably damaging	Het
Spaca3	G	T	11: 80,754,847 (GRCm39)	R96L	possibly damaging	Het
Stat1	A	G	1: 52,188,081 (GRCm39)	N495S	probably benign	Het
Tas2r130	T	C	6: 131,607,270 (GRCm39)	N175S	probably benign	Het
Tcaf2	A	G	6: 42,606,472 (GRCm39)	L494P	probably damaging	Het
Tdrd12	C	A	7: 35,179,561 (GRCm39)		probably null	Het
Thbs1	A	G	2: 117,949,837 (GRCm39)	N604S	probably damaging	Het
Togaram1	T	C	12: 65,055,454 (GRCm39)	F1482L	probably benign	Het
Trhr2	A	T	8: 123,087,114 (GRCm39)	S109T	probably damaging	Het
Trpc3	A	T	3: 36,678,562 (GRCm39)	M841K	probably damaging	Het
Tubgcp5	C	T	7: 55,473,315 (GRCm39)	R798C	probably benign	Het
Xirp2	T	A	2: 67,347,173 (GRCm39)	M3138K	probably benign	Het
Zdhhc4	G	A	5: 143,307,646 (GRCm39)	T125I	probably benign	Het
Zfp239	T	A	6: 117,848,716 (GRCm39)	C151*	probably null	Het
Zfp473	C	T	7: 44,382,627 (GRCm39)	E569K	not run	Het
Zzef1	T	A	11: 72,777,516 (GRCm39)	D1782E	probably damaging	Het

Other mutations in Hmgcr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00557:Hmgcr	APN	13	96,795,786 (GRCm39)	missense	probably benign
IGL01369:Hmgcr	APN	13	96,803,030 (GRCm39)	missense	probably null	1.00
IGL01575:Hmgcr	APN	13	96,793,103 (GRCm39)	missense	possibly damaging	0.56
IGL02183:Hmgcr	APN	13	96,799,635 (GRCm39)	missense	probably damaging	1.00
IGL02515:Hmgcr	APN	13	96,803,020 (GRCm39)	splice site	probably benign
IGL02716:Hmgcr	APN	13	96,796,520 (GRCm39)	critical splice acceptor site	probably null
IGL03278:Hmgcr	APN	13	96,793,270 (GRCm39)	splice site	probably benign
IGL03367:Hmgcr	APN	13	96,802,361 (GRCm39)	missense	probably damaging	0.98
PIT4131001:Hmgcr	UTSW	13	96,795,562 (GRCm39)	missense	probably damaging	1.00
PIT4504001:Hmgcr	UTSW	13	96,799,605 (GRCm39)	missense	possibly damaging	0.95
R0003:Hmgcr	UTSW	13	96,788,653 (GRCm39)	missense	probably damaging	1.00
R0017:Hmgcr	UTSW	13	96,788,597 (GRCm39)	splice site	probably benign
R0017:Hmgcr	UTSW	13	96,788,597 (GRCm39)	splice site	probably benign
R0217:Hmgcr	UTSW	13	96,788,488 (GRCm39)	missense	probably damaging	1.00
R0511:Hmgcr	UTSW	13	96,796,651 (GRCm39)	splice site	probably null
R0707:Hmgcr	UTSW	13	96,787,151 (GRCm39)	unclassified	probably benign
R1301:Hmgcr	UTSW	13	96,795,528 (GRCm39)	missense	probably damaging	0.97
R2203:Hmgcr	UTSW	13	96,793,141 (GRCm39)	missense	probably damaging	1.00
R2204:Hmgcr	UTSW	13	96,793,141 (GRCm39)	missense	probably damaging	1.00
R2433:Hmgcr	UTSW	13	96,802,393 (GRCm39)	missense	probably damaging	1.00
R2938:Hmgcr	UTSW	13	96,799,576 (GRCm39)	missense	probably damaging	0.99
R3159:Hmgcr	UTSW	13	96,802,355 (GRCm39)	missense	probably damaging	1.00
R3737:Hmgcr	UTSW	13	96,787,571 (GRCm39)	missense	probably damaging	1.00
R3752:Hmgcr	UTSW	13	96,799,624 (GRCm39)	missense	probably damaging	1.00
R3837:Hmgcr	UTSW	13	96,795,597 (GRCm39)	missense	probably benign	0.19
R3838:Hmgcr	UTSW	13	96,795,597 (GRCm39)	missense	probably benign	0.19
R3839:Hmgcr	UTSW	13	96,795,597 (GRCm39)	missense	probably benign	0.19
R4034:Hmgcr	UTSW	13	96,787,571 (GRCm39)	missense	probably damaging	1.00
R4035:Hmgcr	UTSW	13	96,787,571 (GRCm39)	missense	probably damaging	1.00
R4210:Hmgcr	UTSW	13	96,796,729 (GRCm39)	missense	probably damaging	1.00
R4783:Hmgcr	UTSW	13	96,802,701 (GRCm39)	missense	probably damaging	1.00
R4820:Hmgcr	UTSW	13	96,796,700 (GRCm39)	missense	probably damaging	1.00
R5090:Hmgcr	UTSW	13	96,787,098 (GRCm39)	missense	probably benign
R5113:Hmgcr	UTSW	13	96,793,240 (GRCm39)	missense	probably benign	0.00
R5209:Hmgcr	UTSW	13	96,803,020 (GRCm39)	splice site	probably benign
R5354:Hmgcr	UTSW	13	96,791,404 (GRCm39)	missense	probably benign	0.26
R5571:Hmgcr	UTSW	13	96,803,171 (GRCm39)	missense	probably benign	0.11
R5804:Hmgcr	UTSW	13	96,802,695 (GRCm39)	missense	probably damaging	0.98
R5886:Hmgcr	UTSW	13	96,796,691 (GRCm39)	missense	probably damaging	1.00
R6340:Hmgcr	UTSW	13	96,802,366 (GRCm39)	missense	probably damaging	1.00
R6638:Hmgcr	UTSW	13	96,795,490 (GRCm39)	missense	probably benign
R6699:Hmgcr	UTSW	13	96,796,717 (GRCm39)	missense	probably damaging	1.00
R7024:Hmgcr	UTSW	13	96,795,418 (GRCm39)	missense	probably benign	0.10
R7061:Hmgcr	UTSW	13	96,802,656 (GRCm39)	missense	possibly damaging	0.64
R7286:Hmgcr	UTSW	13	96,803,105 (GRCm39)	missense	probably damaging	1.00
R7705:Hmgcr	UTSW	13	96,793,231 (GRCm39)	missense	probably benign	0.01
R7709:Hmgcr	UTSW	13	96,799,605 (GRCm39)	missense	possibly damaging	0.95
R9034:Hmgcr	UTSW	13	96,795,885 (GRCm39)	missense	probably damaging	1.00
R9158:Hmgcr	UTSW	13	96,792,170 (GRCm39)	nonsense	probably null
R9253:Hmgcr	UTSW	13	96,796,645 (GRCm39)	missense	probably damaging	1.00
R9474:Hmgcr	UTSW	13	96,796,403 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGGTTGCAGCATTCTCATAATG -3'
(R):5'- CTGCGTTACAACTGTTAAGGTGG -3'

Sequencing Primer
(F):5'- AAAACTTACTTTCAGCCCTGGC -3'
(R):5'- GTTACAACTGTTAAGGTGGTCAGAAC -3'

Posted On

2019-06-26