Incidental Mutation 'R4034:Hmgcr'
ID 313639
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 040962-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4034 (G1)
Quality Score 225
Status Not validated
Chromosome 13
Chromosomal Location 96785475-96807444 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to G at 96787571 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Phenylalanine at position 852 (L852F)
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: L852F

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: L852F

DomainStartEndE-ValueType
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: ENSMUST00000169202
SMART Domains Protein: ENSMUSP00000132155
Gene: ENSMUSG00000021670

DomainStartEndE-ValueType
Pfam:HMG-CoA_red 35 219 8.8e-76 PFAM
Predicted Effect unknown
Transcript: ENSMUST00000169945
AA Change: L129F
SMART Domains Protein: ENSMUSP00000128642
Gene: ENSMUSG00000021670
AA Change: L129F

DomainStartEndE-ValueType
Pfam:HMG-CoA_red 1 96 1.8e-37 PFAM
Pfam:HMG-CoA_red 96 148 2.8e-17 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000170287
SMART Domains Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670

DomainStartEndE-ValueType
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 0.6467 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 94.7%
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: 28 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
9930111J21Rik2 A T 11: 48,910,108 (GRCm39) L775* probably null Het
Aarsd1 C T 11: 101,302,158 (GRCm39) V301I probably damaging Het
Arap1 A T 7: 101,049,484 (GRCm39) Y982F possibly damaging Het
Aspa T C 11: 73,199,597 (GRCm39) K227E possibly damaging Het
Ccdc168 A G 1: 44,098,026 (GRCm39) V1024A probably benign Het
Ccdc88c G A 12: 100,896,783 (GRCm39) A1389V possibly damaging Het
Cngb1 C A 8: 95,991,078 (GRCm39) C708F possibly damaging Het
Csn1s2a A G 5: 87,929,746 (GRCm39) Q115R probably benign Het
Cwf19l2 A T 9: 3,456,803 (GRCm39) H712L probably benign Het
Eml6 C A 11: 29,753,137 (GRCm39) V925L probably benign Het
Fbll1 G A 11: 35,688,505 (GRCm39) H253Y possibly damaging Het
Ltbp2 A T 12: 84,851,248 (GRCm39) C836S probably damaging Het
Mroh9 A G 1: 162,908,122 (GRCm39) probably null Het
Muc5ac G A 7: 141,353,581 (GRCm39) probably null Het
Or2y1 A G 11: 49,386,287 (GRCm39) D309G possibly damaging Het
Pgm5 T A 19: 24,839,021 (GRCm39) I45F probably damaging Het
Ppl T C 16: 4,924,721 (GRCm39) T115A probably benign Het
Sgpp1 A G 12: 75,762,964 (GRCm39) Y406H probably damaging Het
Srsf4 C T 4: 131,627,413 (GRCm39) probably benign Het
St18 G A 1: 6,925,697 (GRCm39) probably null Het
Tcerg1 T A 18: 42,652,598 (GRCm39) N75K unknown Het
Tmco4 T C 4: 138,748,172 (GRCm39) Y251H probably damaging Het
Usp42 C T 5: 143,701,194 (GRCm39) S943N probably benign Het
Utp20 C T 10: 88,598,668 (GRCm39) V103I probably benign Het
Vmn1r14 G A 6: 57,211,310 (GRCm39) R252H possibly damaging Het
Wapl T C 14: 34,459,871 (GRCm39) V1013A possibly damaging Het
Zfp37 G A 4: 62,109,933 (GRCm39) T414I probably damaging Het
Zfp423 A G 8: 88,507,972 (GRCm39) C666R probably damaging Het
Other mutations in Hmgcr
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- TGTCAGAAGACCACAAGGCC -3'
(R):5'- CCAGCGTTTCTAATGGAGTTTAGGG -3'

Sequencing Primer
(F):5'- TCAGTAGCCTGGAACTTGCCAAG -3'
(R):5'- GAGTTTAGGGCTCCTTCTCCG -3'
Posted On 2015-04-30