Incidental Mutation 'R4820:Hmgcr'
ID 370168
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 042436-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4820 (G1)
Quality Score 225
Status Validated
Chromosome 13
Chromosomal Location 96785475-96807444 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 96796700 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glycine to Serine at position 197 (G197S)
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: G197S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: G197S

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 damaging
Transcript: ENSMUST00000169196
AA Change: G197S

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000132749
Gene: ENSMUSG00000021670
AA Change: G197S

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 probably benign
Transcript: ENSMUST00000169202
SMART Domains Protein: ENSMUSP00000132155
Gene: ENSMUSG00000021670

DomainStartEndE-ValueType
Pfam:HMG-CoA_red 35 219 8.8e-76 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000170287
AA Change: G197S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: G197S

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 0.2153 question?
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 98.3%
  • 10x: 96.5%
  • 20x: 92.9%
Validation Efficiency 96% (104/108)
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930488N24Rik T C 17: 14,326,481 (GRCm39) noncoding transcript Het
5730455P16Rik A T 11: 80,266,346 (GRCm39) S132T possibly damaging Het
Aadacl3 T A 4: 144,184,527 (GRCm39) H77L probably damaging Het
Actr5 T A 2: 158,467,426 (GRCm39) V122D probably damaging Het
Adamts7 A G 9: 90,071,739 (GRCm39) D678G possibly damaging Het
Alpk1 T A 3: 127,464,708 (GRCm39) D1190V probably benign Het
Apbb1ip A T 2: 22,765,265 (GRCm39) N649Y unknown Het
Atp6v0a1 A G 11: 100,933,776 (GRCm39) I522V probably benign Het
Brd10 T C 19: 29,695,809 (GRCm39) N1228S possibly damaging Het
Cars1 T C 7: 143,124,301 (GRCm39) D375G probably damaging Het
Catspere1 A T 1: 177,687,441 (GRCm39) noncoding transcript Het
Ccdc87 A G 19: 4,890,579 (GRCm39) D357G probably damaging Het
Cd101 A T 3: 100,929,471 (GRCm39) S8T probably benign Het
Cfap65 C T 1: 74,966,791 (GRCm39) A299T probably benign Het
Cic T C 7: 24,971,157 (GRCm39) V296A possibly damaging Het
Col7a1 T A 9: 108,797,675 (GRCm39) S1686T possibly damaging Het
Ctbp2 A C 7: 132,615,423 (GRCm39) L504R probably damaging Het
Cttnbp2nl T C 3: 104,918,640 (GRCm39) K67E probably benign Het
Cyp2c50 C T 19: 40,102,024 (GRCm39) P480S probably damaging Het
Dcdc5 A C 2: 106,166,420 (GRCm39) noncoding transcript Het
Defb2 G T 8: 22,333,317 (GRCm39) E31* probably null Het
Dhrs1 T A 14: 55,977,083 (GRCm39) N244I possibly damaging Het
Dop1b A G 16: 93,589,978 (GRCm39) I134V probably benign Het
Eif1ad11 A T 12: 87,994,158 (GRCm39) I129F unknown Het
Etl4 A G 2: 20,811,496 (GRCm39) D1193G possibly damaging Het
Ezh1 A C 11: 101,094,594 (GRCm39) S399R probably damaging Het
Fam161a T C 11: 22,970,076 (GRCm39) S26P probably damaging Het
Fcgbp C A 7: 27,813,383 (GRCm39) S2306Y probably damaging Het
Fras1 T C 5: 96,876,512 (GRCm39) I2415T probably benign Het
Gas2l3 A G 10: 89,252,907 (GRCm39) L246P probably damaging Het
Gdf15 C T 8: 71,082,246 (GRCm39) V287M probably damaging Het
Gm7742 T C 17: 21,420,235 (GRCm39) noncoding transcript Het
Grin2d T C 7: 45,507,363 (GRCm39) D446G probably damaging Het
Hemk1 A G 9: 107,205,385 (GRCm39) F107L probably benign Het
Ift52 G A 2: 162,873,108 (GRCm39) G207D probably benign Het
Il17re A G 6: 113,442,816 (GRCm39) T275A probably benign Het
Iqcf3 T C 9: 106,430,788 (GRCm39) probably benign Het
Kcna1 A G 6: 126,619,099 (GRCm39) I407T probably damaging Het
Kcnrg T A 14: 61,845,386 (GRCm39) M142K probably benign Het
Lhx9 C A 1: 138,766,105 (GRCm39) V237L probably benign Het
Lipo3 A C 19: 33,560,497 (GRCm39) I56S probably damaging Het
Loxhd1 C G 18: 77,472,663 (GRCm39) P1060R probably damaging Het
Map2k4 A C 11: 65,587,201 (GRCm39) probably benign Het
Methig1 A G 15: 100,251,416 (GRCm39) K109R possibly damaging Het
Mmrn1 G A 6: 60,950,027 (GRCm39) V326I probably benign Het
Myo15a G A 11: 60,367,741 (GRCm39) R167H probably damaging Het
Ncoa7 G A 10: 30,524,472 (GRCm39) T142M probably damaging Het
Nfkb2 C A 19: 46,296,493 (GRCm39) Q254K probably damaging Het
Nherf1 A G 11: 115,070,918 (GRCm39) E290G probably benign Het
Nol6 G T 4: 41,121,508 (GRCm39) P278Q probably damaging Het
Nptxr T A 15: 79,677,027 (GRCm39) D285V probably damaging Het
Oosp3 T C 19: 11,688,997 (GRCm39) W82R probably damaging Het
Or6b3 A T 1: 92,438,812 (GRCm39) *313K probably null Het
Or6n1 A G 1: 173,916,742 (GRCm39) I45M possibly damaging Het
Pa2g4 G T 10: 128,395,199 (GRCm39) T322K probably damaging Het
Parp16 C A 9: 65,145,175 (GRCm39) F291L probably damaging Het
Pdzd9 A T 7: 120,267,619 (GRCm39) D65E probably damaging Het
Pgap3 A G 11: 98,281,300 (GRCm39) W238R probably damaging Het
Pgf G A 12: 85,218,538 (GRCm39) H67Y probably benign Het
Pik3cb T C 9: 98,955,679 (GRCm39) T413A probably benign Het
Plcxd2 A T 16: 45,800,700 (GRCm39) C175S probably benign Het
Pou2f1 A T 1: 165,719,517 (GRCm39) probably benign Het
Ppfia1 T G 7: 144,052,106 (GRCm39) N846T probably benign Het
Ppid T A 3: 79,502,504 (GRCm39) probably null Het
Prkcq G A 2: 11,231,797 (GRCm39) probably null Het
Ptgds T C 2: 25,359,058 (GRCm39) K66E probably benign Het
Ptpmt1 A G 2: 90,748,283 (GRCm39) noncoding transcript Het
Rab3il1 G A 19: 10,004,034 (GRCm39) G51D probably benign Het
Rdx T C 9: 51,974,891 (GRCm39) V9A probably damaging Het
Rpl7l1 T C 17: 47,089,014 (GRCm39) N239S probably benign Het
Rrbp1 C A 2: 143,806,685 (GRCm39) A978S possibly damaging Het
Rsf1 GCGGCGGCG GCGGCGGCGCCGGCGGCG 7: 97,229,126 (GRCm39) probably benign Het
Scn3a A T 2: 65,291,622 (GRCm39) I1708N probably damaging Het
Serinc1 A G 10: 57,401,466 (GRCm39) I109T possibly damaging Het
Shroom1 G A 11: 53,355,966 (GRCm39) V339I probably benign Het
Slc30a8 T A 15: 52,169,880 (GRCm39) C36S probably benign Het
Slco1b2 A G 6: 141,631,158 (GRCm39) I597M probably benign Het
Snx27 A G 3: 94,427,518 (GRCm39) F228S probably damaging Het
Spata31f1a T A 4: 42,851,815 (GRCm39) I114F probably damaging Het
Speer4e2 G T 5: 15,026,225 (GRCm39) T144K probably benign Het
Stim1 T A 7: 102,064,571 (GRCm39) F214I probably damaging Het
Svep1 T C 4: 58,082,664 (GRCm39) T1987A probably benign Het
Tamm41 A G 6: 115,002,378 (GRCm39) I18T possibly damaging Het
Tmem150b T A 7: 4,726,871 (GRCm39) D79V probably damaging Het
Tmem167 T A 13: 90,252,548 (GRCm39) I68N probably benign Het
Traf3 A G 12: 111,227,204 (GRCm39) E339G possibly damaging Het
Tspan12 G A 6: 21,795,660 (GRCm39) P177S probably damaging Het
Ttn A G 2: 76,783,562 (GRCm39) I810T probably benign Het
Ulk1 T C 5: 110,939,996 (GRCm39) T407A probably benign Het
Uroc1 G A 6: 90,334,600 (GRCm39) probably null Het
Vmn2r-ps69 T C 7: 84,959,584 (GRCm39) noncoding transcript Het
Wdr59 T C 8: 112,207,446 (GRCm39) N476S probably benign Het
Zfp472 A G 17: 33,196,416 (GRCm39) M164V probably benign Het
Zfp608 T C 18: 55,120,756 (GRCm39) N277S probably benign Het
Zfp831 T C 2: 174,547,097 (GRCm39) C1427R possibly 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
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
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'- CAAATTGGACGACCCTCACG -3'
(R):5'- GCCATAGATCATCTTTGTGTTGC -3'

Sequencing Primer
(F):5'- ACCCTCACGGCTTTCACGAG -3'
(R):5'- AGATCATCTTTGTGTTGCTAATTTTG -3'
Posted On 2016-02-04