Incidental Mutation 'R0206:Mvk'
ID 35452
Institutional Source Beutler Lab
Gene Symbol Mvk
Ensembl Gene ENSMUSG00000041939
Gene Name mevalonate kinase
Synonyms 2310010A05Rik
MMRRC Submission 038459-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0206 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 114582330-114598652 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 114597035 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Methionine at position 334 (T334M)
Ref Sequence ENSEMBL: ENSMUSP00000107858 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000043760] [ENSMUST00000112239] [ENSMUST00000125650] [ENSMUST00000139420]
AlphaFold Q9R008
Predicted Effect probably damaging
Transcript: ENSMUST00000043760
AA Change: T322M

PolyPhen 2 Score 0.958 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000036971
Gene: ENSMUSG00000041939
AA Change: T322M

DomainStartEndE-ValueType
low complexity region 108 118 N/A INTRINSIC
Pfam:GHMP_kinases_N 130 212 7.6e-26 PFAM
Pfam:GHMP_kinases_C 291 365 2.1e-6 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000112239
AA Change: T334M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000107858
Gene: ENSMUSG00000041939
AA Change: T334M

DomainStartEndE-ValueType
low complexity region 120 130 N/A INTRINSIC
Pfam:GHMP_kinases_N 142 224 1.6e-25 PFAM
Pfam:GHMP_kinases_C 303 377 8.2e-8 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000125120
Predicted Effect probably benign
Transcript: ENSMUST00000125650
SMART Domains Protein: ENSMUSP00000114611
Gene: ENSMUSG00000041939

DomainStartEndE-ValueType
low complexity region 120 130 N/A INTRINSIC
Pfam:GHMP_kinases_N 142 224 1.3e-27 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000139420
SMART Domains Protein: ENSMUSP00000142376
Gene: ENSMUSG00000041939

DomainStartEndE-ValueType
PDB:2R42|A 1 62 6e-30 PDB
SCOP:d1kvka1 2 31 1e-10 SMART
Meta Mutation Damage Score 0.6467 question?
Coding Region Coverage
  • 1x: 98.2%
  • 3x: 97.1%
  • 10x: 94.6%
  • 20x: 89.0%
Validation Efficiency 99% (83/84)
MGI Phenotype FUNCTION: This gene encodes mevalonate kinase, a key enzyme involved in the biosynthesis of cholesterol and non-sterol isoprenes. The complete lack of encoded protein is lethal to mouse embryos. Mice lacking one allele of this gene exhibit increased levels of mevalonate in spleen, heart and kidney, as well as increased levels of serum immunoglobulins A and D. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Allele List at MGI
Other mutations in this stock
Total: 76 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A530064D06Rik G A 17: 48,470,486 (GRCm39) T165I probably benign Het
Aadacl2fm1 C T 3: 59,840,110 (GRCm39) R61C probably damaging Het
Acsl5 A G 19: 55,269,001 (GRCm39) K221E probably benign Het
Adam26a A C 8: 44,023,455 (GRCm39) F12V possibly damaging Het
Adgrb2 T C 4: 129,886,352 (GRCm39) L164P probably damaging Het
Aldh1l1 T C 6: 90,546,848 (GRCm39) F384L possibly damaging Het
Arhgef5 A G 6: 43,250,275 (GRCm39) E342G probably damaging Het
Btbd8 A G 5: 107,652,906 (GRCm39) T304A probably benign Het
Cacna1b A G 2: 24,497,492 (GRCm39) S2140P probably damaging Het
Camsap2 G C 1: 136,208,738 (GRCm39) P918R probably damaging Het
Cdca3 C T 6: 124,809,514 (GRCm39) probably benign Het
Cenpj G T 14: 56,801,427 (GRCm39) A182E probably benign Het
Cit A T 5: 116,132,089 (GRCm39) N1782Y possibly damaging Het
Cmya5 A G 13: 93,232,065 (GRCm39) S1008P probably damaging Het
Csgalnact2 T G 6: 118,091,347 (GRCm39) Q197P probably benign Het
D630045J12Rik A G 6: 38,116,385 (GRCm39) M1745T probably damaging Het
Ddt A G 10: 75,608,719 (GRCm39) M1T probably null Het
Dnah11 A C 12: 118,007,509 (GRCm39) N2156K probably damaging Het
Dock3 G T 9: 106,874,195 (GRCm39) Y425* probably null Het
Eng A T 2: 32,569,005 (GRCm39) T511S probably benign Het
Gabra6 C T 11: 42,207,906 (GRCm39) W188* probably null Het
Gnptab A T 10: 88,275,372 (GRCm39) H1111L probably damaging Het
H2-M10.4 A G 17: 36,771,375 (GRCm39) W268R probably damaging Het
Hrct1 C A 4: 43,727,384 (GRCm39) T8K possibly damaging Het
Il2ra T C 2: 11,686,828 (GRCm39) probably benign Het
Inhca A G 9: 103,159,861 (GRCm39) C5R probably damaging Het
Inpp5k T C 11: 75,521,969 (GRCm39) I15T probably benign Het
Ipcef1 A G 10: 6,870,062 (GRCm39) S113P probably damaging Het
Kctd8 A T 5: 69,498,508 (GRCm39) V46E probably damaging Het
Klk1b9 T A 7: 43,628,854 (GRCm39) N119K possibly damaging Het
Krtap9-3 C A 11: 99,488,663 (GRCm39) C73F probably damaging Het
Loxhd1 T A 18: 77,492,562 (GRCm39) F1334L possibly damaging Het
Me3 A T 7: 89,498,868 (GRCm39) T483S probably benign Het
Med1 A G 11: 98,046,515 (GRCm39) probably benign Het
Med13 A G 11: 86,191,682 (GRCm39) probably benign Het
Mxra8 T A 4: 155,927,053 (GRCm39) I329N probably damaging Het
Mybphl T C 3: 108,282,731 (GRCm39) V207A probably damaging Het
Myom1 T C 17: 71,344,292 (GRCm39) S266P probably damaging Het
Nr2f2 G C 7: 70,009,923 (GRCm39) P52R probably damaging Het
Or1d2 A T 11: 74,255,968 (GRCm39) I158F probably benign Het
Or2ag12 A G 7: 106,276,781 (GRCm39) V304A probably benign Het
Or52b1 A T 7: 104,979,090 (GRCm39) M103K possibly damaging Het
Or5b105 G A 19: 13,080,642 (GRCm39) R3C possibly damaging Het
Or5m3 T C 2: 85,838,636 (GRCm39) I172T probably damaging Het
Or6f1 T C 7: 85,970,854 (GRCm39) Y102C probably benign Het
Pcdhb18 T C 18: 37,623,240 (GRCm39) I190T possibly damaging Het
Pgbd1 A C 13: 21,618,651 (GRCm39) L2R probably damaging Het
Pkp4 A G 2: 59,096,780 (GRCm39) I61V probably damaging Het
Pold4 T G 19: 4,282,593 (GRCm39) Y58* probably null Het
Pomgnt1 T C 4: 116,015,757 (GRCm39) probably null Het
Prex2 T A 1: 11,355,368 (GRCm39) D1556E probably damaging Het
Psmd1 T C 1: 86,061,463 (GRCm39) V891A possibly damaging Het
Psme3ip1 A G 8: 95,314,639 (GRCm39) F73S probably damaging Het
Rlig1 T A 10: 100,422,056 (GRCm39) K69* probably null Het
Rmdn2 T A 17: 79,957,716 (GRCm39) probably benign Het
Ryr2 A G 13: 11,691,137 (GRCm39) probably benign Het
Scgb2b27 C A 7: 33,711,562 (GRCm39) E96* probably null Het
Sec16b G T 1: 157,380,505 (GRCm39) G359* probably null Het
Slc1a3 A G 15: 8,738,040 (GRCm39) probably benign Het
Slc28a1 A T 7: 80,767,454 (GRCm39) probably benign Het
Slc35d1 T C 4: 103,065,351 (GRCm39) T177A probably damaging Het
Snx33 G A 9: 56,833,508 (GRCm39) S187L probably damaging Het
Spg11 C T 2: 121,886,177 (GRCm39) probably null Het
Spint1 T C 2: 119,078,826 (GRCm39) probably benign Het
Spta1 A G 1: 174,020,526 (GRCm39) H545R probably damaging Het
Tinag A G 9: 76,907,134 (GRCm39) I367T probably damaging Het
Tln1 C T 4: 43,549,151 (GRCm39) V644M probably damaging Het
Tnfrsf21 C T 17: 43,349,104 (GRCm39) H239Y probably benign Het
Ube4b T C 4: 149,483,094 (GRCm39) H58R probably benign Het
Ush2a A C 1: 188,263,958 (GRCm39) I1612L probably damaging Het
Usp28 A G 9: 48,939,569 (GRCm39) Y275C probably damaging Het
Vmn2r6 T C 3: 64,447,333 (GRCm39) T578A probably benign Het
Vps13c A G 9: 67,846,444 (GRCm39) probably benign Het
Vwf T C 6: 125,614,419 (GRCm39) F1100S probably damaging Het
Zfp318 G T 17: 46,709,945 (GRCm39) R556L probably benign Het
Zkscan1 T A 5: 138,099,448 (GRCm39) C391S probably damaging Het
Other mutations in Mvk
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00493:Mvk APN 5 114,583,502 (GRCm39) missense probably benign 0.00
IGL01615:Mvk APN 5 114,584,353 (GRCm39) missense probably benign 0.41
IGL02735:Mvk APN 5 114,588,880 (GRCm39) missense probably benign 0.00
R1474:Mvk UTSW 5 114,598,157 (GRCm39) missense probably damaging 0.99
R2511:Mvk UTSW 5 114,588,459 (GRCm39) nonsense probably null
R4377:Mvk UTSW 5 114,591,022 (GRCm39) intron probably benign
R4861:Mvk UTSW 5 114,598,258 (GRCm39) intron probably benign
R4902:Mvk UTSW 5 114,594,060 (GRCm39) missense probably benign 0.05
R5073:Mvk UTSW 5 114,591,013 (GRCm39) intron probably benign
R5355:Mvk UTSW 5 114,590,499 (GRCm39) missense probably damaging 1.00
R5411:Mvk UTSW 5 114,597,034 (GRCm39) missense probably benign 0.00
R5637:Mvk UTSW 5 114,594,003 (GRCm39) missense possibly damaging 0.47
R5687:Mvk UTSW 5 114,588,826 (GRCm39) missense probably damaging 1.00
R6778:Mvk UTSW 5 114,590,441 (GRCm39) missense probably benign 0.01
R7402:Mvk UTSW 5 114,594,039 (GRCm39) missense possibly damaging 0.79
R8305:Mvk UTSW 5 114,588,840 (GRCm39) missense probably damaging 1.00
Z1088:Mvk UTSW 5 114,596,995 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- AGAGAGCGTGAGCTGTCCCAAATC -3'
(R):5'- ATGAGCTTTTCAGCCACAGGCTCC -3'

Sequencing Primer
(F):5'- GAACAGATGACCCCTCTTCTAG -3'
(R):5'- acagggacacagggagg -3'
Genotyping

Genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the mutation.
 

PCR Primers

R02060016_PCR_F: 5’- AGAGAGCGTGAGCTGTCCCAAATC-3’

R02060016_PCR_R: 5’- ATGAGCTTTTCAGCCACAGGCTCC-3’

Sequencing Primers

R02060016_SEQ_F: 5’- GAACAGATGACCCCTCTTCTAG-3’
 

R02060016_SEQ_R: 5’- acagggacacagggagg-3’
 

PCR program

1) 94°C             2:00

2) 94°C             0:30

3) 55°C             0:30

4) 72°C             1:00

5) repeat steps (2-4) 40X

6) 72°C             10:00

7) 4°C               hold

The following sequence of 488 nucleotides is amplified (NCBI RefSeq: NC_000071, chromosome 5:29637356-29637764):

agagagcgtg agctgtccca aatcagcagc tgccaggtgg acaggcaacc tgggatgcga       

cagagggctc gccctgggtg ggcccaggca ggaacagatg acccctcttc taggagctga      

tagacatgaa ccagcaccat ctgaatgctc tcggggtggg ccacaactcc ctggaccagc       

tctgccaagt aacggcagca cacggactgc acagcaagct gacgggcgct ggcggtggcg      

gctgtggcat caccctcctg aagccaggta cgtgatatgc ggcctgctag gtgtctggtt      

gccagtgtga actgtggtgg agggtccgca ggagaatccc ctagaggggg gaagacttga      

gctctgctct gtggccttga gcaagtgagt tgacctccct gtgtccctgt gggaaagcat      

ggatgatagc aggtagacta ctggaccatt gctccccgcc aggaggagcc tgtggctgaa      

aagctcat

Primer binding sites are underlined and the sequencing primer is highlighted; the mutated nucleotide is shown in red text.
Posted On 2013-05-09