Mutagenetix > Incidental Mutations

Incidental Mutation 'R3838:Hmgcr'

277018

Institutional Source

Beutler Lab

Gene Symbol

Hmgcr

Ensembl Gene

ENSMUSG00000021670

Gene Name

3-hydroxy-3-methylglutaryl-Coenzyme A reductase

Synonyms

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

MMRRC Submission

040779-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R3838 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

96648967-96670936 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 96659089 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 324 (I324T)

Ref Sequence

ENSEMBL: ENSMUSP00000128939 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022176] [ENSMUST00000168855] [ENSMUST00000169196] [ENSMUST00000169202] [ENSMUST00000170287]

Predicted Effect

probably benign
Transcript: ENSMUST00000022176
AA Change: I324T

PolyPhen 2 Score 0.122 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: I324T

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

noncoding transcript
Transcript: ENSMUST00000163201

Predicted Effect

probably benign
Transcript: ENSMUST00000168855

Predicted Effect

probably benign
Transcript: ENSMUST00000169196

SMART Domains

Protein: ENSMUSP00000132749
Gene: ENSMUSG00000021670

Domain	Start	End	E-Value	Type
transmembrane domain	20	37	N/A	INTRINSIC
transmembrane domain	57	79	N/A	INTRINSIC
Pfam:Sterol-sensing	85	210	4.7e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000169202

SMART Domains

Protein: ENSMUSP00000132155
Gene: ENSMUSG00000021670

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

Predicted Effect

probably benign
Transcript: ENSMUST00000170287
AA Change: I324T

PolyPhen 2 Score 0.190 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: I324T

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

Meta Mutation Damage Score

0.3729

Coding Region Coverage

1x: 99.3%
3x: 98.8%
10x: 97.8%
20x: 96.4%

Validation Efficiency

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700042G07Rik	A	G	4: 116,173,521	T41A	probably benign	Het
4930486L24Rik	A	G	13: 60,845,227	Y213H	probably damaging	Het
Alg8	C	T	7: 97,388,545	H379Y	probably damaging	Het
Arhgef25	T	C	10: 127,189,736	T12A	probably benign	Het
Arid4a	A	G	12: 71,075,785	E980G	possibly damaging	Het
Aspm	C	T	1: 139,478,054	H1560Y	probably benign	Het
Atg10	A	T	13: 90,937,380	I150K	probably damaging	Het
Bud13	A	C	9: 46,290,192	Q387P	possibly damaging	Het
Champ1	A	G	8: 13,879,939	Y699C	probably damaging	Het
Clstn1	A	G	4: 149,638,333	E476G	probably damaging	Het
Col2a1	T	C	15: 97,988,976	D345G	unknown	Het
Col2a1	A	T	15: 98,000,581		probably benign	Het
Col9a2	C	G	4: 121,054,258	R599G	probably damaging	Het
Dnajb2	G	A	1: 75,241,480		probably null	Het
Dock4	G	T	12: 40,794,624		probably null	Het
Epx	A	T	11: 87,874,830	L101Q	probably damaging	Het
F13a1	A	T	13: 37,047,424	N21K	probably damaging	Het
Fam13c	C	T	10: 70,542,648	S336L	probably damaging	Het
Fam35a	T	C	14: 34,245,368	D77G	probably benign	Het
Foxj3	T	A	4: 119,616,624	H215Q	possibly damaging	Het
Gcnt4	A	T	13: 96,947,014	R273*	probably null	Het
Gpam	T	C	19: 55,080,458	N450S	probably benign	Het
Hivep2	C	A	10: 14,128,969	T437K	probably benign	Het
Hmcn2	T	C	2: 31,413,407	L3020P	probably damaging	Het
Ighmbp2	T	C	19: 3,271,658	Y367C	probably benign	Het
Lrrc14b	A	G	13: 74,363,545	C139R	possibly damaging	Het
Lsamp	A	T	16: 42,134,312	E174V	possibly damaging	Het
Mid1ip1	T	C	X: 10,718,381	V51A	possibly damaging	Het
Mrc2	G	A	11: 105,348,431		probably null	Het
Msn	C	A	X: 96,160,199	Q303K	probably damaging	Het
Myh7b	A	G	2: 155,632,989	K1816E	probably damaging	Het
Nap1l1	T	A	10: 111,495,322		probably null	Het
Nme2	T	A	11: 93,949,977	E252D	probably benign	Het
Ntpcr	G	A	8: 125,737,372	V79M	probably damaging	Het
Ogdh	C	T	11: 6,338,627	R235*	probably null	Het
Olfr1490	A	G	19: 13,654,957	D176G	probably benign	Het
Olfr825	C	A	10: 130,162,406	E307*	probably null	Het
Olfr959	A	G	9: 39,572,971	V96A	probably benign	Het
Pcdh20	T	C	14: 88,468,463	N467S	probably benign	Het
Pkhd1	G	A	1: 20,534,629	T1154I	possibly damaging	Het
Polq	G	T	16: 37,078,349	R2157I	probably damaging	Het
Reep6	C	A	10: 80,335,889	A533E	probably damaging	Het
Senp2	T	C	16: 22,009,735	S32P	probably damaging	Het
Sept11	T	A	5: 93,148,399	I52N	probably damaging	Het
Slc17a4	C	T	13: 23,901,769	R387H	probably benign	Het
Spdye4b	C	T	5: 143,192,329	T11I	probably benign	Het
Srrt	C	T	5: 137,302,125		probably null	Het
Sspo	T	A	6: 48,480,820	C3085S	probably damaging	Het
Stim1	C	T	7: 102,411,296	T182I	possibly damaging	Het
Thbs2	C	A	17: 14,687,851	V217L	probably benign	Het
Thpo	G	A	16: 20,728,748	R38C	probably damaging	Het
Tmem210	A	G	2: 25,288,432	E35G	possibly damaging	Het
Trim12c	T	A	7: 104,340,868		probably benign	Het
Tvp23b	A	G	11: 62,883,629	H33R	possibly damaging	Het
Usp14	A	G	18: 10,024,532		probably null	Het
Vmn2r73	A	G	7: 85,858,050	W685R	probably benign	Het
Zfp618	G	A	4: 63,133,564	A861T	probably benign	Het
Zfp715	A	G	7: 43,299,756	V260A	probably benign	Het

Other mutations in Hmgcr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00557:Hmgcr	APN	13	96659278	missense	probably benign
IGL01369:Hmgcr	APN	13	96666522	missense	probably null	1.00
IGL01575:Hmgcr	APN	13	96656595	missense	possibly damaging	0.56
IGL02183:Hmgcr	APN	13	96663127	missense	probably damaging	1.00
IGL02515:Hmgcr	APN	13	96666512	splice site	probably benign
IGL02716:Hmgcr	APN	13	96660012	critical splice acceptor site	probably null
IGL03278:Hmgcr	APN	13	96656762	splice site	probably benign
IGL03367:Hmgcr	APN	13	96665853	missense	probably damaging	0.98
PIT4131001:Hmgcr	UTSW	13	96659054	missense	probably damaging	1.00
PIT4504001:Hmgcr	UTSW	13	96663097	missense	possibly damaging	0.95
R0003:Hmgcr	UTSW	13	96652145	missense	probably damaging	1.00
R0017:Hmgcr	UTSW	13	96652089	splice site	probably benign
R0017:Hmgcr	UTSW	13	96652089	splice site	probably benign
R0217:Hmgcr	UTSW	13	96651980	missense	probably damaging	1.00
R0511:Hmgcr	UTSW	13	96660143	unclassified	probably null
R0707:Hmgcr	UTSW	13	96650643	unclassified	probably benign
R1301:Hmgcr	UTSW	13	96659020	missense	probably damaging	0.97
R2203:Hmgcr	UTSW	13	96656633	missense	probably damaging	1.00
R2204:Hmgcr	UTSW	13	96656633	missense	probably damaging	1.00
R2433:Hmgcr	UTSW	13	96665885	missense	probably damaging	1.00
R2938:Hmgcr	UTSW	13	96663068	missense	probably damaging	0.99
R3159:Hmgcr	UTSW	13	96665847	missense	probably damaging	1.00
R3737:Hmgcr	UTSW	13	96651063	missense	probably damaging	1.00
R3752:Hmgcr	UTSW	13	96663116	missense	probably damaging	1.00
R3837:Hmgcr	UTSW	13	96659089	missense	probably benign	0.19
R3839:Hmgcr	UTSW	13	96659089	missense	probably benign	0.19
R4034:Hmgcr	UTSW	13	96651063	missense	probably damaging	1.00
R4035:Hmgcr	UTSW	13	96651063	missense	probably damaging	1.00
R4210:Hmgcr	UTSW	13	96660221	missense	probably damaging	1.00
R4783:Hmgcr	UTSW	13	96666193	missense	probably damaging	1.00
R4820:Hmgcr	UTSW	13	96660192	missense	probably damaging	1.00
R5090:Hmgcr	UTSW	13	96650590	missense	probably benign
R5113:Hmgcr	UTSW	13	96656732	missense	probably benign	0.00
R5209:Hmgcr	UTSW	13	96666512	splice site	probably benign
R5354:Hmgcr	UTSW	13	96654896	missense	probably benign	0.26
R5571:Hmgcr	UTSW	13	96666663	missense	probably benign	0.11
R5804:Hmgcr	UTSW	13	96666187	missense	probably damaging	0.98
R5886:Hmgcr	UTSW	13	96660183	missense	probably damaging	1.00
R6340:Hmgcr	UTSW	13	96665858	missense	probably damaging	1.00
R6638:Hmgcr	UTSW	13	96658982	missense	probably benign
R6699:Hmgcr	UTSW	13	96660209	missense	probably damaging	1.00
R7024:Hmgcr	UTSW	13	96658910	missense	probably benign	0.10
R7061:Hmgcr	UTSW	13	96666148	missense	possibly damaging	0.64
R7284:Hmgcr	UTSW	13	96652665	missense	probably damaging	1.00
R7286:Hmgcr	UTSW	13	96666597	missense	probably damaging	1.00
R7705:Hmgcr	UTSW	13	96656723	missense	probably benign	0.01
R7709:Hmgcr	UTSW	13	96663097	missense	possibly damaging	0.95

Predicted Primers

PCR Primer
(F):5'- TCTACTGACGAAAGCTTCTGG -3'
(R):5'- GCAGGCTAAGGTTTCCTTGG -3'

Sequencing Primer
(F):5'- TGGTTCCTTCTCACAAGCAGAGG -3'
(R):5'- TCTGGACGAAGATGTGTCCAAG -3'

Posted On

2015-04-06