Incidental Mutation 'R2204:Hmgcr'
ID 238929
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 040206-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2204 (G1)
Quality Score 225
Status Not validated
Chromosome 13
Chromosomal Location 96785475-96807444 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 96793141 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Proline at position 497 (L497P)
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: L497P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: L497P

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 noncoding transcript
Transcript: ENSMUST00000163201
Predicted Effect probably benign
Transcript: ENSMUST00000168855
Predicted Effect probably benign
Transcript: ENSMUST00000169196
SMART Domains Protein: ENSMUSP00000132749
Gene: ENSMUSG00000021670

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000169202
AA Change: L12P

PolyPhen 2 Score 0.886 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000132155
Gene: ENSMUSG00000021670
AA Change: L12P

DomainStartEndE-ValueType
Pfam:HMG-CoA_red 35 219 8.8e-76 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000169945
SMART Domains Protein: ENSMUSP00000128642
Gene: ENSMUSG00000021670

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 damaging
Transcript: ENSMUST00000170287
AA Change: L497P

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: L497P

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
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.8%
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: 62 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A630076J17Rik A G 3: 107,140,943 (GRCm39) probably benign Het
Abca1 G A 4: 53,090,291 (GRCm39) T386I probably damaging Het
Acsf3 C T 8: 123,540,383 (GRCm39) S527F probably damaging Het
Adamts7 A T 9: 90,062,729 (GRCm39) K394N probably damaging Het
Ankrd2 C A 19: 42,032,558 (GRCm39) A273E probably damaging Het
Ankrd26 T A 6: 118,500,843 (GRCm39) H876L possibly damaging Het
Atg16l1 A C 1: 87,694,737 (GRCm39) Q138P probably benign Het
Bap1 T C 14: 30,978,658 (GRCm39) V23A probably benign Het
Cartpt A T 13: 100,037,133 (GRCm39) S4T probably benign Het
Cdan1 C A 2: 120,551,241 (GRCm39) C1093F probably damaging Het
Ceacam11 C T 7: 17,709,273 (GRCm39) T157I possibly damaging Het
Cfap45 T C 1: 172,359,728 (GRCm39) V76A probably benign Het
Chil3 T C 3: 106,071,562 (GRCm39) D34G probably benign Het
Chrnb4 G A 9: 54,951,132 (GRCm39) R44C probably damaging Het
Col6a4 T C 9: 105,937,331 (GRCm39) D1395G probably damaging Het
Cpa1 A G 6: 30,641,818 (GRCm39) D214G probably damaging Het
Cttnbp2 T G 6: 18,408,693 (GRCm39) D976A probably benign Het
Elapor1 C T 3: 108,382,359 (GRCm39) G270E probably damaging Het
Espl1 A G 15: 102,214,340 (GRCm39) E693G probably damaging Het
Fat1 G T 8: 45,476,737 (GRCm39) A1928S probably damaging Het
Fiz1 C T 7: 5,011,685 (GRCm39) E278K probably benign Het
Flnc C T 6: 29,459,507 (GRCm39) P2536S probably damaging Het
Gm6370 T A 5: 146,430,539 (GRCm39) D241E probably benign Het
Hlcs T C 16: 94,032,011 (GRCm39) T451A probably benign Het
Hmgcs2 T A 3: 98,198,499 (GRCm39) I134N probably damaging Het
Ifit1bl1 C T 19: 34,571,741 (GRCm39) E239K probably benign Het
Ift52 G A 2: 162,873,150 (GRCm39) S221N probably benign Het
Knstrn T A 2: 118,661,456 (GRCm39) probably null Het
Map3k14 T A 11: 103,130,280 (GRCm39) K212N possibly damaging Het
Ndufb7 A G 8: 84,297,528 (GRCm39) H61R probably damaging Het
Nop56 T A 2: 130,119,488 (GRCm39) I51N probably damaging Het
Nudt5 A T 2: 5,860,794 (GRCm39) I22F possibly damaging Het
Or10j2 T A 1: 173,097,703 (GRCm39) probably null Het
Or4p23 C G 2: 88,576,953 (GRCm39) G93A probably benign Het
Or7d11 T C 9: 19,966,507 (GRCm39) N84S possibly damaging Het
P3h4 G A 11: 100,304,832 (GRCm39) A185V probably benign Het
Pdcl A T 2: 37,242,056 (GRCm39) N231K probably benign Het
Plcb4 T C 2: 135,844,514 (GRCm39) I144T probably benign Het
Pramel32 A T 4: 88,546,355 (GRCm39) L329Q probably damaging Het
Prrc2b C A 2: 32,113,476 (GRCm39) Q1970K probably damaging Het
Robo4 CGG CG 9: 37,322,786 (GRCm39) probably null Het
Sars2 T C 7: 28,449,099 (GRCm39) V302A possibly damaging Het
Shroom3 G T 5: 93,090,945 (GRCm39) V1151F probably damaging Het
Spata31d1d A G 13: 59,879,435 (GRCm39) C34R possibly damaging Het
Speg A T 1: 75,407,121 (GRCm39) T3137S probably benign Het
Ssh3 A G 19: 4,319,101 (GRCm39) L3P probably damaging Het
Stard9 GAAA GAA 2: 120,529,012 (GRCm39) probably null Het
Stoml2 G T 4: 43,030,243 (GRCm39) Y119* probably null Het
Susd1 A G 4: 59,349,843 (GRCm39) L531P possibly damaging Het
Taco1 C T 11: 105,962,760 (GRCm39) A149V probably benign Het
Tenm3 T C 8: 49,127,585 (GRCm39) E31G probably benign Het
Tmc1 A T 19: 20,918,269 (GRCm39) L2M probably benign Het
Tmem39b A C 4: 129,587,716 (GRCm39) S32A probably benign Het
Tnfsf14 T C 17: 57,497,638 (GRCm39) D198G possibly damaging Het
Trabd2b T C 4: 114,460,191 (GRCm39) L443P probably damaging Het
Trip4 T A 9: 65,771,547 (GRCm39) I328F probably damaging Het
Trpc3 A G 3: 36,704,298 (GRCm39) F553S possibly damaging Het
Tssk2 A G 16: 17,716,603 (GRCm39) D2G possibly damaging Het
Ttn T C 2: 76,601,985 (GRCm39) N18559S possibly damaging Het
Vmn1r23 T C 6: 57,903,604 (GRCm39) D58G probably benign Het
Zbtb47 A G 9: 121,591,703 (GRCm39) T8A possibly damaging Het
Zfyve27 C A 19: 42,171,885 (GRCm39) A139D 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
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
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'- GTTGGACTTTCCCAGGGATG -3'
(R):5'- TGTGAACAGCTCTGCACTGTG -3'

Sequencing Primer
(F):5'- ACTTTCCCAGGGATGATTATAAAATC -3'
(R):5'- GCTCTTCTGCTCATGAACTGC -3'
Posted On 2014-10-02