Mutagenetix > Incidental Mutation

Incidental Mutation 'R5355:Mvk'

424034

Institutional Source

Beutler Lab

Gene Symbol

Mvk

Ensembl Gene

ENSMUSG00000041939

Gene Name

mevalonate kinase

Synonyms

2310010A05Rik

MMRRC Submission

042934-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5355 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

114582330-114598652 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 114590499 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Alanine at position 7 (S7A)

Ref Sequence

ENSEMBL: ENSMUSP00000142376 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000043760] [ENSMUST00000112239] [ENSMUST00000124260] [ENSMUST00000125650] [ENSMUST00000137167] [ENSMUST00000139420]

AlphaFold

Q9R008

Predicted Effect

probably damaging
Transcript: ENSMUST00000043760
AA Change: S201A

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

SMART Domains

Protein: ENSMUSP00000036971
Gene: ENSMUSG00000041939
AA Change: S201A

Domain	Start	End	E-Value	Type
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: S213A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000107858
Gene: ENSMUSG00000041939
AA Change: S213A

Domain	Start	End	E-Value	Type
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

probably damaging
Transcript: ENSMUST00000124260
AA Change: S213A

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

SMART Domains

Protein: ENSMUSP00000143347
Gene: ENSMUSG00000041939
AA Change: S213A

Domain	Start	End	E-Value	Type
low complexity region	120	130	N/A	INTRINSIC
Pfam:GHMP_kinases_N	142	224	5.9e-25	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125120

Predicted Effect

probably damaging
Transcript: ENSMUST00000125650
AA Change: S213A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000114611
Gene: ENSMUSG00000041939
AA Change: S213A

Domain	Start	End	E-Value	Type
low complexity region	120	130	N/A	INTRINSIC
Pfam:GHMP_kinases_N	142	224	1.3e-27	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000137167
AA Change: S201A

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

SMART Domains

Protein: ENSMUSP00000142758
Gene: ENSMUSG00000041939
AA Change: S201A

Domain	Start	End	E-Value	Type
low complexity region	108	118	N/A	INTRINSIC
Pfam:GHMP_kinases_N	130	212	5.2e-25	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000139420
AA Change: S7A

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

SMART Domains

Protein: ENSMUSP00000142376
Gene: ENSMUSG00000041939
AA Change: S7A

Domain	Start	End	E-Value	Type
PDB:2R42\|A	1	62	6e-30	PDB
SCOP:d1kvka1	2	31	1e-10	SMART

Meta Mutation Damage Score

0.9377

Coding Region Coverage

1x: 99.4%
3x: 98.8%
10x: 97.6%
20x: 96.2%

Validation Efficiency

94% (50/53)

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: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1a	T	C	5: 8,776,873 (GRCm39)	L857P	probably damaging	Het
Adam12	T	C	7: 133,489,671 (GRCm39)	*582W	probably null	Het
Adra1d	A	G	2: 131,403,007 (GRCm39)	V361A	probably damaging	Het
Ank2	A	G	3: 126,737,698 (GRCm39)		probably benign	Het
Atxn10	T	A	15: 85,346,515 (GRCm39)	N424K	probably damaging	Het
C8b	A	G	4: 104,637,860 (GRCm39)	T111A	probably benign	Het
Ccdc168	A	C	1: 44,097,139 (GRCm39)	C1320G	possibly damaging	Het
Cdc45	C	T	16: 18,614,647 (GRCm39)	R205H	probably damaging	Het
Cdr2l	T	C	11: 115,284,396 (GRCm39)	V244A	possibly damaging	Het
Col11a2	A	G	17: 34,270,775 (GRCm39)	M468V	probably benign	Het
Col4a2	G	A	8: 11,495,984 (GRCm39)	R1535H	probably damaging	Het
Cryab	A	T	9: 50,664,751 (GRCm39)	S59C	probably damaging	Het
Cuzd1	G	A	7: 130,917,853 (GRCm39)	T249I	probably damaging	Het
Disp2	G	A	2: 118,617,392 (GRCm39)	V129M	probably benign	Het
Dlg2	G	T	7: 91,099,011 (GRCm39)	R31L	probably benign	Het
Dthd1	A	C	5: 62,996,730 (GRCm39)	L488F	probably damaging	Het
Dusp29	G	A	14: 21,727,091 (GRCm39)	R186W	probably benign	Het
Fat2	T	G	11: 55,172,992 (GRCm39)	I2574L	probably damaging	Het
Fchsd1	C	T	18: 38,092,926 (GRCm39)		probably benign	Het
Fryl	T	C	5: 73,231,247 (GRCm39)	D1610G	probably damaging	Het
Gm10330	T	A	12: 23,830,131 (GRCm39)	N17Y	probably damaging	Het
Gm4787	T	A	12: 81,424,239 (GRCm39)	R640*	probably null	Het
H2bc13	A	T	13: 21,900,030 (GRCm39)	I95N	probably damaging	Het
Ift88	T	A	14: 57,675,699 (GRCm39)	S71T	probably benign	Het
Isoc2b	A	G	7: 4,852,357 (GRCm39)		probably benign	Het
Itgb2	G	T	10: 77,393,886 (GRCm39)	R442L	probably benign	Het
Lama5	A	T	2: 179,823,444 (GRCm39)	N2658K	possibly damaging	Het
Lemd3	A	T	10: 120,769,538 (GRCm39)	I598K	probably damaging	Het
Lrp2	A	T	2: 69,285,182 (GRCm39)	C3825*	probably null	Het
Mep1a	T	C	17: 43,788,037 (GRCm39)	D673G	probably damaging	Het
Met	A	G	6: 17,491,361 (GRCm39)	Y41C	probably damaging	Het
Mfn2	A	G	4: 147,979,035 (GRCm39)	V99A	probably damaging	Het
Mmadhc	A	G	2: 50,181,436 (GRCm39)	I78T	probably benign	Het
Mmp9	C	A	2: 164,792,912 (GRCm39)	P389T	possibly damaging	Het
Nlrp1a	T	A	11: 71,015,077 (GRCm39)	T58S	probably benign	Het
Nlrp1c-ps	C	A	11: 71,148,839 (GRCm39)		noncoding transcript	Het
Nr1h3	A	G	2: 91,022,253 (GRCm39)	I125T	possibly damaging	Het
Or2a55-ps1	C	T	6: 43,071,598 (GRCm39)		noncoding transcript	Het
Or8k39	A	T	2: 86,563,680 (GRCm39)	I92K	probably damaging	Het
Parn	A	G	16: 13,485,886 (GRCm39)	I3T	possibly damaging	Het
Parp8	A	G	13: 116,998,740 (GRCm39)		probably null	Het
Parva	T	C	7: 112,143,475 (GRCm39)		probably null	Het
Pwp2	A	C	10: 78,011,378 (GRCm39)	I672M	possibly damaging	Het
Sfswap	C	T	5: 129,616,810 (GRCm39)	T418I	probably benign	Het
Slc6a3	A	G	13: 73,709,078 (GRCm39)	Y334C	probably damaging	Het
Slc7a13	C	A	4: 19,839,267 (GRCm39)	T290K	probably benign	Het
Spry2	A	G	14: 106,130,712 (GRCm39)	L158P	probably damaging	Het
Usp25	A	G	16: 76,847,342 (GRCm39)	E150G	probably damaging	Het
Zfp747	A	G	7: 126,973,769 (GRCm39)	F134L	possibly damaging	Het
Zp3r	A	G	1: 130,524,518 (GRCm39)	F175S	probably benign	Het
Zscan22	C	A	7: 12,640,435 (GRCm39)	N67K	probably benign	Het

Other mutations in Mvk

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R0206:Mvk	UTSW	5	114,597,035 (GRCm39)	missense	probably damaging	1.00
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
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'- CATTGTCACCTTAGGCCGAGAG -3'
(R):5'- GGAGTTCCTATTTCCCAGCC -3'

Sequencing Primer
(F):5'- ATCTGAGTCCCTGTGCCCAG -3'
(R):5'- TTAGAAGCCCCTAACTGG -3'

Posted On

2016-08-04