Mutagenetix > Incidental Mutation

Incidental Mutation 'R9474:Hmgcr'

715669

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9474 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

96648967-96670936 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 96659895 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Arginine at position 260 (M260R)

Ref Sequence

ENSEMBL: ENSMUSP00000022176 (fasta)

Gene Model

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

AlphaFold

Q01237

Predicted Effect

probably damaging
Transcript: ENSMUST00000022176
AA Change: M260R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: M260R

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

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 damaging
Transcript: ENSMUST00000170287
AA Change: M260R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: M260R

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: 99.6%
20x: 98.6%

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610008E11Rik	C	A	10: 79,067,731	K250N	probably damaging	Het
9530077C05Rik	T	C	9: 22,431,719	M303T	probably damaging	Het
Adam5	A	T	8: 24,747,524	D623E	possibly damaging	Het
Akt3	T	C	1: 177,025,386	Y473C	probably damaging	Het
Ankib1	A	G	5: 3,755,617	Y217H	probably damaging	Het
Clca4b	T	A	3: 144,911,166	T908S	probably benign	Het
Clec7a	G	A	6: 129,463,163	Q160*	probably null	Het
Cntnap4	T	A	8: 112,733,471	I152N	probably damaging	Het
Ctdspl	C	T	9: 119,037,377	A179V	probably damaging	Het
Ddx43	T	C	9: 78,406,386	S200P	probably damaging	Het
Dip2c	A	G	13: 9,494,927	D84G	unknown	Het
Dmbt1	G	A	7: 131,074,257	R625H	unknown	Het
Dusp9	TAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAG	TAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAG	X: 73,640,611		probably benign	Het
E2f7	C	T	10: 110,767,189	T355I	probably damaging	Het
E2f7	C	A	10: 110,779,057	L541M	probably damaging	Het
Elovl5	T	A	9: 77,982,725	S273T	possibly damaging	Het
Emc1	T	A	4: 139,366,394	L605Q	probably damaging	Het
Fras1	T	A	5: 96,739,265	D2635E	probably benign	Het
Gabrb1	G	A	5: 72,108,347	G195E	probably damaging	Het
Galm	A	G	17: 80,150,132	D199G	possibly damaging	Het
Galntl6	T	G	8: 57,777,325	S20R	probably damaging	Het
Gm21671	A	T	5: 25,953,138	I72N	probably damaging	Het
Grb14	T	G	2: 64,938,400	Y189S	probably damaging	Het
Hk2	T	A	6: 82,728,914	I803F	probably damaging	Het
Hmcn1	G	A	1: 150,630,720	R3779W	probably damaging	Het
Hsbp1l1	T	A	18: 80,233,424	K68N	possibly damaging	Het
Inhba	A	C	13: 16,017,678	E128A	probably benign	Het
Itpr3	G	A	17: 27,118,677		probably benign	Het
Klhl3	G	A	13: 58,019,459	P364S	probably damaging	Het
Lhpp	T	C	7: 132,641,583	L176P	probably damaging	Het
Lrp1b	C	A	2: 40,601,587	A223S	probably damaging	Het
Lrp3	A	G	7: 35,204,064	F286L	probably damaging	Het
Lrrc7	T	C	3: 158,135,391	T1337A	probably benign	Het
Magi2	A	G	5: 20,195,021	D17G	probably benign	Het
Map3k21	T	C	8: 125,924,164	S302P	probably damaging	Het
Mbtd1	A	G	11: 93,925,685	D386G	probably benign	Het
Mfsd2b	A	T	12: 4,866,820	D306E	possibly damaging	Het
Muc20	T	C	16: 32,794,083	E308G	probably damaging	Het
Myh13	G	A	11: 67,364,886	S34N		Het
Nebl	C	A	2: 17,369,610	G894*	probably null	Het
Nelfa	A	G	5: 33,898,751	Y523H	probably damaging	Het
Ninj1	A	G	13: 49,187,600	D13G	probably benign	Het
Ninl	A	T	2: 150,940,806	S170T	probably benign	Het
Nlrp4c	G	A	7: 6,065,627	V176M	possibly damaging	Het
Nobox	G	A	6: 43,307,181	R144C	probably damaging	Het
Oas1a	G	A	5: 120,899,254	L237F	probably damaging	Het
Olfr1099	A	G	2: 86,959,413	M15T	probably benign	Het
Olfr1153	T	C	2: 87,896,349	M50T	probably benign	Het
Olfr1254	A	C	2: 89,789,162	Y63*	probably null	Het
Olfr1348	A	G	7: 6,502,151	L25P	probably benign	Het
Olfr1356	T	C	10: 78,847,057	N286S	probably damaging	Het
Olfr625-ps1	A	T	7: 103,683,270	Y184F	probably damaging	Het
Orai1	A	G	5: 123,029,238	N158S	probably damaging	Het
Pa2g4	C	A	10: 128,563,098	V121L	probably benign	Het
Pclo	T	C	5: 14,521,236	S212P	possibly damaging	Het
Plce1	G	A	19: 38,777,893	E2121K	possibly damaging	Het
Plg	A	G	17: 12,403,137	Y448C	probably damaging	Het
Plppr4	A	T	3: 117,323,217	N330K	probably damaging	Het
Pou2f2	A	G	7: 25,094,822	L373S	probably benign	Het
Rnpep	A	G	1: 135,283,603	F136L	probably benign	Het
Rp1	A	G	1: 4,092,615		probably null	Het
Shank1	G	A	7: 44,312,918	S71N	unknown	Het
Slc5a4a	GCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGC	GCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGCCTTGC	10: 76,150,404		probably benign	Het
Slc5a5	T	C	8: 70,884,952	D574G	probably benign	Het
Slc7a15	T	A	12: 8,538,794	N251I	probably damaging	Het
Susd4	T	C	1: 182,892,100	S427P	probably benign	Het
Tarbp1	T	A	8: 126,429,040	T1320S	probably benign	Het
Tbpl2	C	T	2: 24,094,638	V166I	probably benign	Het
Thbs1	T	C	2: 118,120,037		probably null	Het
Tnfsf13b	A	G	8: 10,031,648	Y270C	probably damaging	Het
Vps11	G	T	9: 44,348,993	C857*	probably null	Het
Vsig10	G	A	5: 117,325,039	R110H	probably benign	Het
Wee2	T	A	6: 40,455,110	Y204*	probably null	Het
Zfpm2	T	A	15: 41,103,471	S1117R	probably damaging	Het
Zscan5b	A	G	7: 6,231,473	N166S	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	splice site	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
R3838: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
R9034:Hmgcr	UTSW	13	96659377	missense	probably damaging	1.00
R9158:Hmgcr	UTSW	13	96655662	nonsense	probably null
R9253:Hmgcr	UTSW	13	96660137	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGTCTGTTCAGGAGAGCAAG -3'
(R):5'- AGTAGTACTTCCCATGCTGCC -3'

Sequencing Primer
(F):5'- TTGTATCCCAGCACTCAGGG -3'
(R):5'- ATGCTGCCCCTCTCCTTAG -3'

Posted On

2022-06-15