Mutagenetix > Incidental Mutation

Incidental Mutation 'R7126:Mthfd2'

552321

Institutional Source

Beutler Lab

Gene Symbol

Mthfd2

Ensembl Gene

ENSMUSG00000005667

Gene Name

methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase

Synonyms

NMDMC

MMRRC Submission

045213-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7126 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

83282673-83302890 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 83290472 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 53 (V53A)

Ref Sequence

ENSEMBL: ENSMUSP00000005810 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005810] [ENSMUST00000203847] [ENSMUST00000204472]

AlphaFold

P18155

Predicted Effect

probably benign
Transcript: ENSMUST00000005810
AA Change: V53A

PolyPhen 2 Score 0.023 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000005810
Gene: ENSMUSG00000005667
AA Change: V53A

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
Pfam:THF_DHG_CYH	39	155	8.1e-45	PFAM
Pfam:THF_DHG_CYH_C	158	332	7.7e-65	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000203847
AA Change: V53A

PolyPhen 2 Score 0.796 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000145266
Gene: ENSMUSG00000005667
AA Change: V53A

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
Pfam:THF_DHG_CYH	39	108	2e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000204472
AA Change: V34A

PolyPhen 2 Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000145222
Gene: ENSMUSG00000005667
AA Change: V34A

Domain	Start	End	E-Value	Type
Pfam:THF_DHG_CYH	20	97	2.2e-20	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

97% (73/75)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. The enzyme functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate. Formation of the enzyme-magnesium complex allows binding of NAD. Alternative splicing results in two different transcripts, one protein-coding and the other not protein-coding. This gene has a pseudogene on chromosome 7. [provided by RefSeq, Mar 2009]
PHENOTYPE: Mice homozygous for disruptions in this gene die as embryos before E15.5. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810062G17Rik	T	C	3: 36,535,988 (GRCm39)	C85R	unknown	Het
3110082I17Rik	G	T	5: 139,347,005 (GRCm39)	H153Q	unknown	Het
Acadsb	T	C	7: 131,039,177 (GRCm39)	I316T	probably benign	Het
Acsbg2	A	T	17: 57,153,633 (GRCm39)	N523K	probably damaging	Het
Ahnak	C	T	19: 8,979,723 (GRCm39)	P336S	possibly damaging	Het
Ankdd1b	A	G	13: 96,566,370 (GRCm39)	V277A	possibly damaging	Het
Aspm	A	G	1: 139,408,541 (GRCm39)	Y2476C	probably benign	Het
Atg13	G	A	2: 91,510,765 (GRCm39)	R321W	probably damaging	Het
B4galt2	A	G	4: 117,734,735 (GRCm39)	F211S	probably damaging	Het
Baiap3	T	A	17: 25,464,119 (GRCm39)	T913S	possibly damaging	Het
Btbd18	A	T	2: 84,496,546 (GRCm39)	E61D	possibly damaging	Het
Btnl9	G	T	11: 49,060,082 (GRCm39)	S555R	probably damaging	Het
Cbs	T	A	17: 31,838,113 (GRCm39)	M379L	probably benign	Het
Chd9	G	A	8: 91,741,853 (GRCm39)	G1614D	unknown	Het
Cmya5	G	A	13: 93,226,448 (GRCm39)	P2880L	probably benign	Het
Cnnm1	T	C	19: 43,473,292 (GRCm39)	S729P	probably damaging	Het
Cox16	T	A	12: 81,518,940 (GRCm39)	E70D	probably benign	Het
Cp	A	G	3: 20,034,788 (GRCm39)	H699R	probably damaging	Het
Cyp2d26	T	C	15: 82,678,209 (GRCm39)	N56D	probably benign	Het
Dennd4c	A	G	4: 86,725,667 (GRCm39)	Y707C	probably damaging	Het
Dnah5	A	T	15: 28,349,983 (GRCm39)	E2555D	probably benign	Het
Ess2	T	C	16: 17,729,154 (GRCm39)	T6A	unknown	Het
Filip1	A	G	9: 79,805,577 (GRCm39)	L59P	possibly damaging	Het
Fsip2	A	G	2: 82,813,485 (GRCm39)	N3268S	possibly damaging	Het
Gja10	A	T	4: 32,601,014 (GRCm39)	C457S	probably benign	Het
Gm4779	TCGGGGCCGGGGCCGGGGCCG	TCGGGGCCGGGGCCGGGGCCGGGGCCG	X: 100,837,777 (GRCm39)		probably benign	Het
Gm47959	G	A	1: 82,978,503 (GRCm39)	G57S	unknown	Het
Grep1	C	T	17: 23,939,538 (GRCm39)	V8I	probably benign	Het
Grid2	T	A	6: 64,053,794 (GRCm39)	V331E	probably damaging	Het
Inpp4a	C	A	1: 37,413,353 (GRCm39)	H123Q	probably benign	Het
Ireb2	T	A	9: 54,793,851 (GRCm39)	Y260*	probably null	Het
Itpr2	G	A	6: 146,259,294 (GRCm39)	Q628*	probably null	Het
Kbtbd11	G	A	8: 15,078,759 (GRCm39)	A453T	probably damaging	Het
Kcnj2	A	G	11: 110,963,648 (GRCm39)	T347A	probably damaging	Het
Kif19b	A	T	5: 140,477,073 (GRCm39)	D874V	probably benign	Het
Klhl12	A	G	1: 134,395,521 (GRCm39)	H161R	probably damaging	Het
Krt78	T	C	15: 101,856,871 (GRCm39)	E412G	probably damaging	Het
Lzic	A	G	4: 149,573,132 (GRCm39)	I95V	probably damaging	Het
Mme	C	T	3: 63,276,322 (GRCm39)	P700S	probably damaging	Het
Mroh2a	G	T	1: 88,182,657 (GRCm39)	R1195L	possibly damaging	Het
Mtus1	A	G	8: 41,468,439 (GRCm39)	L210P	probably damaging	Het
Muc16	T	C	9: 18,552,512 (GRCm39)	T4594A	probably benign	Het
Niban1	T	A	1: 151,590,318 (GRCm39)	C537*	probably null	Het
Olfm5	A	T	7: 103,809,187 (GRCm39)	C208S	probably damaging	Het
Or10q1	T	A	19: 13,726,887 (GRCm39)	I139N	possibly damaging	Het
Or2ad1	A	T	13: 21,326,888 (GRCm39)	L113H	probably damaging	Het
Or7a39	T	C	10: 78,715,411 (GRCm39)	V135A	possibly damaging	Het
Parp12	T	C	6: 39,088,670 (GRCm39)	I189V	probably benign	Het
Plin1	T	C	7: 79,376,412 (GRCm39)		probably null	Het
Prl7a1	C	T	13: 27,826,402 (GRCm39)		probably null	Het
Ptpn23	T	C	9: 110,217,812 (GRCm39)	D711G	probably benign	Het
Rgs22	A	T	15: 36,103,954 (GRCm39)	I169N	probably damaging	Het
Scn7a	G	T	2: 66,587,630 (GRCm39)	H24Q	possibly damaging	Het
Scrt2	C	T	2: 151,935,006 (GRCm39)	P53L	probably damaging	Het
Sh3rf1	A	T	8: 61,802,458 (GRCm39)	I264L	probably benign	Het
Smarcd1	A	T	15: 99,607,206 (GRCm39)	D393V	probably damaging	Het
Spag17	T	G	3: 100,008,751 (GRCm39)	N1960K	probably benign	Het
Ssb	A	G	2: 69,696,845 (GRCm39)	T62A	possibly damaging	Het
Taar7b	T	A	10: 23,875,960 (GRCm39)	Y42N	possibly damaging	Het
Terf1	A	T	1: 15,883,363 (GRCm39)	I159L	probably benign	Het
Tff3	T	G	17: 31,346,410 (GRCm39)	N54T	probably benign	Het
Top2a	A	G	11: 98,905,818 (GRCm39)	L285P	probably benign	Het
Trim24	A	G	6: 37,896,392 (GRCm39)	Y283C	probably damaging	Het
Trim58	T	C	11: 58,531,405 (GRCm39)	C38R	probably damaging	Het
Trpa1	T	A	1: 14,960,648 (GRCm39)	T647S	probably benign	Het
Trpm4	A	T	7: 44,960,133 (GRCm39)		probably null	Het
Trpm6	C	T	19: 18,831,397 (GRCm39)	Q1421*	probably null	Het
Ubr2	A	T	17: 47,284,982 (GRCm39)		probably null	Het
Vmn1r46	T	G	6: 89,953,976 (GRCm39)	I275S	possibly damaging	Het
Vmn2r54	A	G	7: 12,366,088 (GRCm39)	F282S	possibly damaging	Het
Vmn2r57	A	G	7: 41,049,218 (GRCm39)	S844P	possibly damaging	Het
Vps13a	A	C	19: 16,688,243 (GRCm39)	C855G	probably benign	Het
Wdr31	T	A	4: 62,381,666 (GRCm39)	Q55L	probably benign	Het

Other mutations in Mthfd2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01825:Mthfd2	APN	6	83,287,493 (GRCm39)	missense	probably benign	0.12
IGL01844:Mthfd2	APN	6	83,288,792 (GRCm39)	critical splice donor site	probably null
IGL02936:Mthfd2	APN	6	83,288,342 (GRCm39)	missense	probably damaging	1.00
R0130:Mthfd2	UTSW	6	83,285,990 (GRCm39)	missense	probably damaging	0.99
R0862:Mthfd2	UTSW	6	83,290,376 (GRCm39)	missense	probably damaging	0.99
R1902:Mthfd2	UTSW	6	83,283,713 (GRCm39)	missense	probably damaging	1.00
R3431:Mthfd2	UTSW	6	83,288,330 (GRCm39)	missense	probably benign	0.30
R3732:Mthfd2	UTSW	6	83,290,457 (GRCm39)	missense	probably damaging	1.00
R4473:Mthfd2	UTSW	6	83,287,517 (GRCm39)	unclassified	probably benign
R5301:Mthfd2	UTSW	6	83,287,465 (GRCm39)	missense	probably damaging	1.00
R5730:Mthfd2	UTSW	6	83,294,441 (GRCm39)	missense	probably benign	0.35
R7594:Mthfd2	UTSW	6	83,283,665 (GRCm39)	missense	probably benign	0.00
R7602:Mthfd2	UTSW	6	83,288,830 (GRCm39)	missense	probably benign	0.01
R7916:Mthfd2	UTSW	6	83,286,455 (GRCm39)	missense	possibly damaging	0.79
R9709:Mthfd2	UTSW	6	83,283,665 (GRCm39)	missense	possibly damaging	0.62

Predicted Primers

PCR Primer
(F):5'- CTCAGAAAGAGGCATGGTGG -3'
(R):5'- GTGACCGCCCTTAATTACCTCC -3'

Sequencing Primer
(F):5'- TGGCACACACCAGGGGG -3'
(R):5'- ACCTGCAGAAATGAAGCC -3'

Posted On

2019-05-15