Mutagenetix > Incidental Mutation

Incidental Mutation 'R9136:Mthfd1'

694040

Institutional Source

Beutler Lab

Gene Symbol

Mthfd1

Ensembl Gene

ENSMUSG00000021048

Gene Name

methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthase

Synonyms

E430024A07Rik, Mthfd, DCS

MMRRC Submission

068931-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9136 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

76302072-76366577 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 76350649 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Arginine at position 677 (M677R)

Ref Sequence

ENSEMBL: ENSMUSP00000021443 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021443] [ENSMUST00000220046] [ENSMUST00000220321]

AlphaFold

Q922D8

Predicted Effect

probably damaging
Transcript: ENSMUST00000021443
AA Change: M677R

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000021443
Gene: ENSMUSG00000021048
AA Change: M677R

Domain	Start	End	E-Value	Type
Pfam:THF_DHG_CYH	6	125	1.7e-36	PFAM
Pfam:THF_DHG_CYH_C	128	295	1.1e-67	PFAM
Pfam:FTHFS	317	935	4.1e-259	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000220046
AA Change: M497R

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)

Predicted Effect

probably benign
Transcript: ENSMUST00000220321

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (71/71)

MGI Phenotype

FUNCTION: This gene encodes a trifunctional cytoplasmic enzyme. The encoded protein functions as a methylenetetrahydrofolate dehydrogenase, a methenyltetrahydrofolate cyclohydrolase, and a formyltetrahydrofolate synthase. The encoded enzyme functions in de novo synthesis of purines and thymidylate and in regeneration of methionine from homocysteine. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a gene trapped allele exhibit embryonic lethality. Mice heterozygous for a gene trap allele exhibit altered amino acid levels and nucleotide metabolism related to dietary folate and choline concentrations. [provided by MGI curators]

Allele List at MGI

All alleles(57) : Targeted, other(2) Gene trapped(54) Radiation induced(1)

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca3	A	G	17: 24,596,807 (GRCm39)	Q420R	probably benign	Het
Abcb9	T	C	5: 124,228,176 (GRCm39)	T22A	possibly damaging	Het
Acsl5	A	T	19: 55,266,400 (GRCm39)	K109N	probably benign	Het
Agpat3	T	C	10: 78,120,893 (GRCm39)	N95S	probably damaging	Het
Akna	C	T	4: 63,310,392 (GRCm39)	D451N	probably damaging	Het
Ankrd17	A	T	5: 90,392,278 (GRCm39)	D1797E	probably damaging	Het
Ano2	A	G	6: 125,959,962 (GRCm39)	N691S	probably damaging	Het
Arrdc1	A	T	2: 24,817,193 (GRCm39)		probably benign	Het
Ccdc63	G	A	5: 122,259,146 (GRCm39)	R251W	probably damaging	Het
Cd70	T	C	17: 57,453,152 (GRCm39)	T171A	possibly damaging	Het
Cenpf	A	T	1: 189,403,352 (GRCm39)	S382T	probably benign	Het
Cox5b-ps	A	C	13: 21,685,587 (GRCm39)	M1R	probably null	Het
Ddx19b	G	T	8: 111,734,906 (GRCm39)	D487E	probably benign	Het
Dlgap4	G	A	2: 156,588,075 (GRCm39)	E640K	possibly damaging	Het
Dtnbp1	A	T	13: 45,084,546 (GRCm39)	F198Y	possibly damaging	Het
Epha10	T	C	4: 124,796,427 (GRCm39)	Y379H		Het
Eral1	A	G	11: 77,964,960 (GRCm39)	I411T		Het
Exd1	C	T	2: 119,359,385 (GRCm39)	G193E	probably damaging	Het
Fat3	C	A	9: 15,833,738 (GRCm39)	A105S		Het
Fbp2	C	T	13: 63,002,840 (GRCm39)	V71M	possibly damaging	Het
Gm10801	C	CGTA	2: 98,494,152 (GRCm39)		probably null	Het
Grm5	G	A	7: 87,689,254 (GRCm39)	V542I	possibly damaging	Het
Hdc	C	T	2: 126,439,786 (GRCm39)		probably null	Het
Hspe1	G	T	1: 55,128,314 (GRCm39)	K36N	probably damaging	Het
Hypk	T	A	2: 121,287,636 (GRCm39)	L17*	probably null	Het
Il18rap	C	T	1: 40,582,177 (GRCm39)	T366M	probably benign	Het
Immt	C	T	6: 71,851,403 (GRCm39)	T588I	probably damaging	Het
Kat2b	T	A	17: 53,936,364 (GRCm39)	S179T	probably benign	Het
Krtap19-5	C	T	16: 88,693,246 (GRCm39)	G22D	unknown	Het
Lipk	A	G	19: 33,999,830 (GRCm39)	D153G	probably damaging	Het
Lnpep	A	G	17: 17,750,090 (GRCm39)	V1000A	probably benign	Het
Map3k7cl	T	C	16: 87,391,227 (GRCm39)	L117P	probably damaging	Het
Meikin	A	G	11: 54,285,464 (GRCm39)	E167G	possibly damaging	Het
Miox	A	G	15: 89,220,740 (GRCm39)	Y215C	probably damaging	Het
Ncoa7	G	A	10: 30,567,628 (GRCm39)	S350L	probably benign	Het
Nox4	G	A	7: 87,025,448 (GRCm39)	R525Q	probably benign	Het
Nrg3	A	T	14: 38,119,262 (GRCm39)	N403K	possibly damaging	Het
Nup210	T	C	6: 91,020,830 (GRCm39)	T955A	possibly damaging	Het
Odf2l	C	A	3: 144,851,698 (GRCm39)	T82K		Het
Or10ag56	A	G	2: 87,139,219 (GRCm39)	I49V	possibly damaging	Het
Or1m1	T	C	9: 18,666,175 (GRCm39)	Y252C	probably damaging	Het
Or4c108	T	A	2: 88,804,113 (GRCm39)	M41L	probably benign	Het
Or8w1	A	G	2: 87,465,341 (GRCm39)	V250A	probably benign	Het
Otud7b	T	A	3: 96,059,815 (GRCm39)		probably benign	Het
Pcm1	C	T	8: 41,732,825 (GRCm39)	S694L	probably benign	Het
Pex11b	T	C	3: 96,551,259 (GRCm39)	L248P	probably damaging	Het
Pira13	A	T	7: 3,826,285 (GRCm39)	I236N		Het
Ppp3cb	T	C	14: 20,581,867 (GRCm39)	I49M	probably benign	Het
Prorp	C	T	12: 55,350,727 (GRCm39)	P12L	probably benign	Het
Prr14l	A	C	5: 32,986,080 (GRCm39)	C1138W		Het
Prss1	T	G	6: 41,438,280 (GRCm39)		probably benign	Het
Psg22	T	A	7: 18,460,811 (GRCm39)	I480K	probably damaging	Het
Rgs21	A	C	1: 144,412,653 (GRCm39)	F57C		Het
Rngtt	T	A	4: 33,404,218 (GRCm39)	D468E	probably damaging	Het
Rorb	A	T	19: 18,934,686 (GRCm39)	V313E	probably damaging	Het
Sdk2	A	G	11: 113,697,203 (GRCm39)	F1736S	probably damaging	Het
Sertad2	A	T	11: 20,598,425 (GRCm39)	E207V	probably benign	Het
Slitrk1	T	C	14: 109,148,981 (GRCm39)	I577V		Het
Sos2	C	A	12: 69,633,446 (GRCm39)	E1143D	possibly damaging	Het
Spen	T	C	4: 141,249,623 (GRCm39)	D55G	unknown	Het
Stoml1	C	A	9: 58,168,236 (GRCm39)	Q316K	possibly damaging	Het
Synpo2l	C	T	14: 20,715,857 (GRCm39)	A243T	probably damaging	Het
Tenm4	A	T	7: 96,473,125 (GRCm39)	I974F	possibly damaging	Het
Trp53bp1	T	A	2: 121,067,092 (GRCm39)	I545F	possibly damaging	Het
Unc13a	T	C	8: 72,104,994 (GRCm39)	D756G	possibly damaging	Het
Uqcrc1	A	G	9: 108,776,973 (GRCm39)	N393D	possibly damaging	Het
Vcl	T	A	14: 21,057,344 (GRCm39)	D505E	probably benign	Het
Vwf	A	T	6: 125,576,356 (GRCm39)		probably benign	Het
Wdr11	A	G	7: 129,204,816 (GRCm39)	H207R		Het
Zc3h7b	A	G	15: 81,653,312 (GRCm39)	D72G	probably damaging	Het
Zfp507	A	T	7: 35,475,883 (GRCm39)	D813E	probably damaging	Het
Zfp704	T	C	3: 9,509,324 (GRCm39)	S374G	probably benign	Het
Zfp97	G	A	17: 17,365,215 (GRCm39)	C238Y	probably benign	Het

Other mutations in Mthfd1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00591:Mthfd1	APN	12	76,347,213 (GRCm39)	missense	possibly damaging	0.79
IGL01996:Mthfd1	APN	12	76,350,679 (GRCm39)	missense	probably damaging	1.00
IGL02399:Mthfd1	APN	12	76,364,406 (GRCm39)	missense	probably damaging	1.00
IGL02529:Mthfd1	APN	12	76,350,483 (GRCm39)	missense	probably benign	0.02
3-1:Mthfd1	UTSW	12	76,361,174 (GRCm39)	critical splice acceptor site	probably null
R0062:Mthfd1	UTSW	12	76,344,363 (GRCm39)	splice site	probably benign
R0062:Mthfd1	UTSW	12	76,344,363 (GRCm39)	splice site	probably benign
R0732:Mthfd1	UTSW	12	76,340,948 (GRCm39)	missense	probably damaging	1.00
R1572:Mthfd1	UTSW	12	76,317,193 (GRCm39)	nonsense	probably null
R1918:Mthfd1	UTSW	12	76,361,750 (GRCm39)	missense	probably damaging	1.00
R2008:Mthfd1	UTSW	12	76,344,293 (GRCm39)	missense	probably damaging	1.00
R2280:Mthfd1	UTSW	12	76,327,266 (GRCm39)	missense	probably benign	0.37
R2857:Mthfd1	UTSW	12	76,335,699 (GRCm39)	missense	probably damaging	0.99
R2859:Mthfd1	UTSW	12	76,335,699 (GRCm39)	missense	probably damaging	0.99
R2997:Mthfd1	UTSW	12	76,361,810 (GRCm39)	missense	probably benign	0.01
R3034:Mthfd1	UTSW	12	76,336,244 (GRCm39)	missense	probably benign	0.04
R3153:Mthfd1	UTSW	12	76,358,737 (GRCm39)	missense	probably benign
R3412:Mthfd1	UTSW	12	76,350,523 (GRCm39)	splice site	probably null
R4135:Mthfd1	UTSW	12	76,329,648 (GRCm39)	splice site	probably null
R4245:Mthfd1	UTSW	12	76,348,047 (GRCm39)	missense	probably damaging	0.99
R4498:Mthfd1	UTSW	12	76,361,764 (GRCm39)	missense	probably damaging	1.00
R4573:Mthfd1	UTSW	12	76,340,912 (GRCm39)	critical splice acceptor site	probably null
R5022:Mthfd1	UTSW	12	76,341,148 (GRCm39)	missense	probably damaging	1.00
R5022:Mthfd1	UTSW	12	76,348,102 (GRCm39)	missense	probably damaging	1.00
R5037:Mthfd1	UTSW	12	76,340,914 (GRCm39)	missense	probably damaging	1.00
R5455:Mthfd1	UTSW	12	76,348,062 (GRCm39)	missense	probably benign	0.20
R5879:Mthfd1	UTSW	12	76,340,992 (GRCm39)	missense	probably benign	0.00
R5902:Mthfd1	UTSW	12	76,337,826 (GRCm39)	missense	probably benign	0.01
R6119:Mthfd1	UTSW	12	76,350,447 (GRCm39)	missense	probably damaging	1.00
R6199:Mthfd1	UTSW	12	76,350,454 (GRCm39)	missense	probably damaging	1.00
R6199:Mthfd1	UTSW	12	76,335,685 (GRCm39)	missense	probably damaging	1.00
R6931:Mthfd1	UTSW	12	76,350,472 (GRCm39)	missense	probably benign
R7405:Mthfd1	UTSW	12	76,358,648 (GRCm39)	missense	probably damaging	0.98
R7658:Mthfd1	UTSW	12	76,317,209 (GRCm39)	missense	probably damaging	1.00
R8053:Mthfd1	UTSW	12	76,327,282 (GRCm39)	missense	probably damaging	1.00
R8493:Mthfd1	UTSW	12	76,340,929 (GRCm39)	missense	probably damaging	1.00
R8914:Mthfd1	UTSW	12	76,329,710 (GRCm39)	missense	probably benign	0.00
R9002:Mthfd1	UTSW	12	76,350,754 (GRCm39)	missense	probably benign	0.00
R9003:Mthfd1	UTSW	12	76,350,754 (GRCm39)	missense	probably benign	0.00
R9004:Mthfd1	UTSW	12	76,350,754 (GRCm39)	missense	probably benign	0.00
R9019:Mthfd1	UTSW	12	76,350,754 (GRCm39)	missense	probably benign	0.00
R9103:Mthfd1	UTSW	12	76,350,517 (GRCm39)	missense	probably damaging	1.00
X0012:Mthfd1	UTSW	12	76,361,182 (GRCm39)	missense	possibly damaging	0.75
Z1176:Mthfd1	UTSW	12	76,350,741 (GRCm39)	missense	possibly damaging	0.95

Predicted Primers

PCR Primer
(F):5'- CTTTCGCCAACATTGCACACG -3'
(R):5'- GGCAGACCCAGAGATATGTC -3'

Sequencing Primer
(F):5'- ATCATTGCAGACCGGATTGC -3'
(R):5'- CATGAAATTTCCTTCAAGCACCTGG -3'

Posted On

2022-01-20