Mutagenetix > Incidental Mutation

Incidental Mutation 'R4783:Hmgcr'

366754

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

042416-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4783 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

96785475-96807444 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 96802701 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Methionine at position 66 (T66M)

Ref Sequence

ENSEMBL: ENSMUSP00000022176 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022176] [ENSMUST00000168855] [ENSMUST00000169196] [ENSMUST00000169966] [ENSMUST00000170287] [ENSMUST00000171537]

AlphaFold

Q01237

Predicted Effect

probably damaging
Transcript: ENSMUST00000022176
AA Change: T66M

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

SMART Domains

Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: T66M

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

noncoding transcript
Transcript: ENSMUST00000168374

Predicted Effect

probably benign
Transcript: ENSMUST00000168855

Predicted Effect

probably damaging
Transcript: ENSMUST00000169196
AA Change: T66M

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000132749
Gene: ENSMUSG00000021670
AA Change: T66M

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 damaging
Transcript: ENSMUST00000169966
AA Change: T66M

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

SMART Domains

Protein: ENSMUSP00000128294
Gene: ENSMUSG00000021670
AA Change: T66M

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
transmembrane domain	57	79	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000170287
AA Change: T66M

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

SMART Domains

Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: T66M

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000171537
AA Change: T76M

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

SMART Domains

Protein: ENSMUSP00000126959
Gene: ENSMUSG00000021670
AA Change: T76M

Domain	Start	End	E-Value	Type
transmembrane domain	20	42	N/A	INTRINSIC
transmembrane domain	67	89	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000172440

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.6%

Validation Efficiency

100% (99/99)

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: 95 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3110082J24Rik	G	A	5: 30,310,198 (GRCm39)	R54*	probably null	Het
Acsl6	A	T	11: 54,227,819 (GRCm39)	M350L	probably damaging	Het
Adgrv1	T	C	13: 81,243,564 (GRCm39)	T6279A	probably damaging	Het
Ago3	A	T	4: 126,262,296 (GRCm39)	M418K	probably benign	Het
Ascc2	G	A	11: 4,596,653 (GRCm39)	R58H	probably benign	Het
Brinp3	A	G	1: 146,603,378 (GRCm39)		probably benign	Het
Carmil3	T	C	14: 55,738,778 (GRCm39)		probably null	Het
Ccdc47	T	A	11: 106,094,430 (GRCm39)	H7L	probably benign	Het
Ccndbp1	A	T	2: 120,839,003 (GRCm39)	T5S	probably benign	Het
Cdr2	A	T	7: 120,557,644 (GRCm39)	F294I	probably benign	Het
Chd8	C	A	14: 52,442,825 (GRCm39)	C575F	probably damaging	Het
Ctsll3	G	A	13: 60,948,209 (GRCm39)	T156I	probably damaging	Het
Dgcr8	G	A	16: 18,076,174 (GRCm39)	R4*	probably null	Het
Dnah1	T	A	14: 30,985,436 (GRCm39)	K3818N	probably damaging	Het
Dok2	C	T	14: 71,015,314 (GRCm39)	P347L	probably benign	Het
Elf1	T	A	14: 79,818,183 (GRCm39)	N567K	probably benign	Het
Emsy	T	C	7: 98,295,686 (GRCm39)	N72S	possibly damaging	Het
Fam76a	A	G	4: 132,643,501 (GRCm39)	Y78H	probably damaging	Het
Fam76a	A	T	4: 132,629,428 (GRCm39)		probably null	Het
Fbn1	A	T	2: 125,166,839 (GRCm39)	C2026S	probably damaging	Het
Fbxo4	T	C	15: 3,998,523 (GRCm39)	T312A	probably benign	Het
Fhip1a	G	T	3: 85,595,877 (GRCm39)	T115K	probably damaging	Het
Flnb	A	T	14: 7,905,701 (GRCm38)	E1150D	probably benign	Het
Galt	T	C	4: 41,758,189 (GRCm39)	V318A	probably damaging	Het
Git1	T	G	11: 77,390,663 (GRCm39)	L133R	probably damaging	Het
Gm11168	G	A	9: 3,006,915 (GRCm39)	M213I	probably benign	Het
Gm7233	A	G	14: 43,037,423 (GRCm39)	E25G	probably benign	Het
Golga2	T	A	2: 32,187,168 (GRCm39)	N89K	probably damaging	Het
Grin1	T	A	2: 25,182,393 (GRCm39)	H956L	possibly damaging	Het
Hlcs	C	T	16: 94,069,398 (GRCm39)	V164I	possibly damaging	Het
Ifi206	A	T	1: 173,308,432 (GRCm39)	H521Q	probably benign	Het
Lgals3bp	G	A	11: 118,284,340 (GRCm39)	T413I	probably damaging	Het
Lrrc7	A	G	3: 157,832,850 (GRCm39)		probably null	Het
Mapk11	T	C	15: 89,033,691 (GRCm39)	Y9C	probably damaging	Het
Mccc1	C	A	3: 36,030,022 (GRCm39)	M429I	probably damaging	Het
Metrnl	A	G	11: 121,598,750 (GRCm39)	E40G	probably benign	Het
Mrgpra1	A	G	7: 46,985,218 (GRCm39)	S154P	probably damaging	Het
Myh13	A	T	11: 67,232,096 (GRCm39)	I459F	probably damaging	Het
Nalf1	T	C	8: 9,258,026 (GRCm39)	Y374C	probably damaging	Het
Nedd4l	C	A	18: 65,305,998 (GRCm39)	D424E	probably damaging	Het
Nid1	C	T	13: 13,674,326 (GRCm39)	R902W	probably damaging	Het
Nphp4	G	A	4: 152,639,003 (GRCm39)	R878K	probably benign	Het
Numa1	A	G	7: 101,662,773 (GRCm39)	T1997A	probably damaging	Het
Nutm1	G	A	2: 112,079,281 (GRCm39)	A878V	probably benign	Het
Nxf1	G	A	19: 8,744,162 (GRCm39)	A339T	probably benign	Het
Oas1b	C	A	5: 120,952,578 (GRCm39)	Q90K	probably benign	Het
Optn	T	C	2: 5,059,438 (GRCm39)	M27V	probably benign	Het
Or1r1	A	G	11: 73,874,834 (GRCm39)	F200S	probably damaging	Het
Or2t35	A	C	14: 14,407,729 (GRCm38)	Y167S	possibly damaging	Het
Or4f56	A	T	2: 111,703,395 (GRCm39)	D268E	possibly damaging	Het
Or5ac17	G	T	16: 59,036,222 (GRCm39)	F251L	probably damaging	Het
Or5d45	A	G	2: 88,153,500 (GRCm39)	I183T	probably damaging	Het
Or5g29	A	G	2: 85,421,282 (GRCm39)	T133A	probably benign	Het
Or5h18	G	T	16: 58,848,260 (GRCm39)	D3E	probably benign	Het
Oxgr1	T	C	14: 120,259,776 (GRCm39)	I144V	probably benign	Het
Pax5	T	A	4: 44,570,086 (GRCm39)	T127S	probably damaging	Het
Pcsk2	T	C	2: 143,529,599 (GRCm39)		probably null	Het
Pdxk	A	G	10: 78,300,626 (GRCm39)	V19A	possibly damaging	Het
Pik3c2a	A	T	7: 116,017,060 (GRCm39)	S232R	probably damaging	Het
Ppip5k1	T	C	2: 121,171,329 (GRCm39)	D620G	possibly damaging	Het
Ppp4r4	T	A	12: 103,557,117 (GRCm39)		probably null	Het
Psmd1	A	G	1: 86,006,434 (GRCm39)	N267D	probably damaging	Het
Pudp	A	G	18: 50,701,136 (GRCm39)	V199A	probably damaging	Het
Rasal3	T	A	17: 32,615,755 (GRCm39)	D361V	probably damaging	Het
Rbm12	T	C	2: 155,938,484 (GRCm39)	D596G	possibly damaging	Het
Rbm6	T	C	9: 107,730,102 (GRCm39)	D182G	probably damaging	Het
Rif1	T	C	2: 52,002,759 (GRCm39)	V2071A	probably damaging	Het
Rilp	C	T	11: 75,401,467 (GRCm39)	A110V	possibly damaging	Het
Rprd2	A	G	3: 95,681,645 (GRCm39)	V332A	probably benign	Het
Sbpl	T	A	17: 24,172,304 (GRCm39)	D205V	unknown	Het
Scn9a	T	C	2: 66,370,967 (GRCm39)	I538V	probably benign	Het
Serpina1d	T	C	12: 103,734,083 (GRCm39)	S74G	possibly damaging	Het
Serpina3n	T	C	12: 104,375,369 (GRCm39)	I147T	possibly damaging	Het
Serpinb8	A	G	1: 107,532,472 (GRCm39)	N188S	probably benign	Het
Sipa1l3	A	G	7: 29,077,066 (GRCm39)	V902A	probably damaging	Het
Slc25a47	T	A	12: 108,821,260 (GRCm39)	L123Q	probably damaging	Het
Slc30a2	A	T	4: 134,071,317 (GRCm39)		probably null	Het
Slc66a1	G	T	4: 139,027,312 (GRCm39)	H343Q	probably benign	Het
Snx13	T	A	12: 35,148,285 (GRCm39)	D271E	probably damaging	Het
Tbc1d9b	A	G	11: 50,062,125 (GRCm39)	N1211S	probably benign	Het
Tdrd3	T	A	14: 87,709,537 (GRCm39)	I67N	probably damaging	Het
Thbs1	T	C	2: 117,945,273 (GRCm39)	V282A	probably benign	Het
Tmc8	A	G	11: 117,682,431 (GRCm39)		probably null	Het
Trim11	T	A	11: 58,879,750 (GRCm39)	F284Y	probably null	Het
Ttn	G	T	2: 76,552,141 (GRCm39)	Y29419*	probably null	Het
Ttn	A	G	2: 76,599,947 (GRCm39)	Y19076H	probably damaging	Het
Ubr4	T	C	4: 139,149,044 (GRCm39)	S448P	possibly damaging	Het
Ugt2b34	T	C	5: 87,039,332 (GRCm39)	E443G	probably damaging	Het
Usp29	A	G	7: 6,964,390 (GRCm39)	T78A	probably damaging	Het
Vmn1r227	A	G	17: 20,955,396 (GRCm39)		noncoding transcript	Het
Vmn1r85	A	T	7: 12,818,788 (GRCm39)	W119R	probably damaging	Het
Vmn2r12	A	T	5: 109,234,379 (GRCm39)	V611E	probably damaging	Het
Vmn2r97	A	T	17: 19,149,550 (GRCm39)	M313L	probably benign	Het
Zap70	T	C	1: 36,818,254 (GRCm39)	Y314H	probably damaging	Het
Zfp667	T	A	7: 6,308,684 (GRCm39)	F451I	possibly 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
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
R7284:Hmgcr	UTSW	13	96,789,173 (GRCm39)	missense	probably damaging	1.00
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'- AGAGTACTAACTGCTGAATGAACC -3'
(R):5'- TCACTCCCTTGAGAAATACAGC -3'

Sequencing Primer
(F):5'- TGAACCCAACACTCTTTCAGTAGTG -3'
(R):5'- GGTCCTTGTTTGAACGC -3'

Posted On

2015-12-29