Mutagenetix > Incidental Mutation

Incidental Mutation 'R0130:Mthfd2'

60530

Institutional Source

Beutler Lab

Gene Symbol

Mthfd2

Ensembl Gene

ENSMUSG00000005667

Gene Name

methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase

Synonyms

NMDMC

MMRRC Submission

038415-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0130 (G1)

Quality Score

153

Status

Validated

Chromosome

Chromosomal Location

83282673-83302890 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 83285990 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 272 (I272F)

Ref Sequence

ENSEMBL: ENSMUSP00000005810 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005810] [ENSMUST00000039212] [ENSMUST00000113899] [ENSMUST00000204472] [ENSMUST00000203847]

AlphaFold

P18155

Predicted Effect

probably damaging
Transcript: ENSMUST00000005810
AA Change: I272F

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000005810
Gene: ENSMUSG00000005667
AA Change: I272F

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

probably benign
Transcript: ENSMUST00000039212

SMART Domains

Protein: ENSMUSP00000041007
Gene: ENSMUSG00000068323

Domain	Start	End	E-Value	Type
Pfam:Band_3_cyto	25	292	5.2e-102	PFAM
low complexity region	321	350	N/A	INTRINSIC
Pfam:HCO3_cotransp	364	884	1.1e-242	PFAM
transmembrane domain	891	913	N/A	INTRINSIC
low complexity region	936	951	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000113899

SMART Domains

Protein: ENSMUSP00000109532
Gene: ENSMUSG00000068323

Domain	Start	End	E-Value	Type
Pfam:Band_3_cyto	25	292	2.9e-102	PFAM
low complexity region	321	350	N/A	INTRINSIC
Pfam:HCO3_cotransp	364	884	5.3e-243	PFAM
transmembrane domain	891	913	N/A	INTRINSIC
low complexity region	936	951	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139802

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141044

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141193

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203375

Predicted Effect

probably benign
Transcript: ENSMUST00000204472

SMART Domains

Protein: ENSMUSP00000145222
Gene: ENSMUSG00000005667

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

Predicted Effect

probably benign
Transcript: ENSMUST00000203847

SMART Domains

Protein: ENSMUSP00000145266
Gene: ENSMUSG00000005667

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

Meta Mutation Damage Score

0.8795

Coding Region Coverage

1x: 99.0%
3x: 97.7%
10x: 93.4%
20x: 80.2%

Validation Efficiency

99% (84/85)

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcg8	A	T	17: 84,994,094 (GRCm39)	Y37F	probably damaging	Het
Ablim2	G	A	5: 35,966,520 (GRCm39)		probably benign	Het
Anxa9	A	G	3: 95,209,733 (GRCm39)	S129P	probably benign	Het
Apol7c	A	G	15: 77,410,562 (GRCm39)	I128T	possibly damaging	Het
Arfgef2	T	G	2: 166,677,639 (GRCm39)	I88S	probably damaging	Het
Arfip2	A	G	7: 105,288,205 (GRCm39)		probably benign	Het
Atp5mf	A	T	5: 145,124,992 (GRCm39)		probably benign	Het
Atp7b	C	T	8: 22,518,188 (GRCm39)	E205K	possibly damaging	Het
Atp8b5	T	A	4: 43,369,715 (GRCm39)		probably null	Het
Cd22	A	G	7: 30,569,389 (GRCm39)	Y402H	possibly damaging	Het
Cd248	A	G	19: 5,119,990 (GRCm39)	T613A	probably benign	Het
Cdcp2	C	T	4: 106,963,904 (GRCm39)		probably benign	Het
Cenpc1	A	T	5: 86,194,405 (GRCm39)	D120E	probably benign	Het
Chd3	T	A	11: 69,250,656 (GRCm39)	H691L	probably damaging	Het
Colec12	C	T	18: 9,858,921 (GRCm39)	P568L	unknown	Het
Cped1	T	A	6: 22,121,038 (GRCm39)	Y373N	probably benign	Het
Cr2	A	T	1: 194,848,539 (GRCm39)	V328D	probably damaging	Het
Ctnnd2	A	T	15: 30,922,059 (GRCm39)	E895V	probably damaging	Het
D630045J12Rik	A	T	6: 38,126,706 (GRCm39)		probably benign	Het
Dcdc2a	A	T	13: 25,371,655 (GRCm39)		probably benign	Het
Dync1h1	C	A	12: 110,585,108 (GRCm39)	T837K	probably benign	Het
Eif2ak3	C	A	6: 70,858,716 (GRCm39)		probably benign	Het
Epb41l5	A	C	1: 119,477,632 (GRCm39)	V705G	possibly damaging	Het
Fat2	T	A	11: 55,142,944 (GRCm39)	M4302L	probably benign	Het
Flnb	T	C	14: 7,901,951 (GRCm38)	V938A	probably damaging	Het
Frmd4a	T	C	2: 4,608,903 (GRCm39)	Y928H	probably damaging	Het
Fyn	C	T	10: 39,387,978 (GRCm39)	T78M	probably benign	Het
Gdap2	A	G	3: 100,109,311 (GRCm39)	T443A	probably damaging	Het
Gde1	A	T	7: 118,294,283 (GRCm39)	F63L	probably benign	Het
Gjc3	A	G	5: 137,956,202 (GRCm39)	S28P	probably benign	Het
Gm10250	G	A	15: 5,150,473 (GRCm39)		probably null	Het
Hp1bp3	C	T	4: 137,964,520 (GRCm39)	S348F	probably damaging	Het
Klhl23	T	C	2: 69,664,310 (GRCm39)	V553A	probably damaging	Het
Lman2l	G	T	1: 36,463,945 (GRCm39)	S171*	probably null	Het
Lrp1b	T	C	2: 41,401,520 (GRCm39)	D378G	probably damaging	Het
Map3k11	T	C	19: 5,740,843 (GRCm39)	L190P	probably damaging	Het
Mki67	T	A	7: 135,298,188 (GRCm39)	Q2282L	probably damaging	Het
Myom1	A	T	17: 71,352,750 (GRCm39)	D358V	probably damaging	Het
Nebl	T	C	2: 17,395,737 (GRCm39)		probably benign	Het
Nebl	T	A	2: 17,397,834 (GRCm39)	Q487H	possibly damaging	Het
Nlrp2	T	A	7: 5,325,417 (GRCm39)	N14Y	possibly damaging	Het
Or14a258	T	C	7: 86,035,514 (GRCm39)	Y118C	probably damaging	Het
Or1j11	T	A	2: 36,312,299 (GRCm39)	D296E	probably benign	Het
Or2z8	C	T	8: 72,812,244 (GRCm39)	T240M	probably damaging	Het
Or5ak22	T	A	2: 85,230,305 (GRCm39)	S191C	probably damaging	Het
Or8k40	T	C	2: 86,584,231 (GRCm39)	M284V	probably benign	Het
Pasd1	T	C	X: 70,983,161 (GRCm39)	C378R	possibly damaging	Het
Paxip1	C	T	5: 27,949,183 (GRCm39)		probably benign	Het
Pclo	A	G	5: 14,729,811 (GRCm39)		probably benign	Het
Pld2	T	G	11: 70,445,174 (GRCm39)	N591K	probably benign	Het
Plekha7	A	G	7: 115,769,939 (GRCm39)	M276T	probably damaging	Het
Prss39	T	A	1: 34,541,281 (GRCm39)		probably benign	Het
Prtg	A	G	9: 72,716,998 (GRCm39)	Y113C	probably damaging	Het
Rab38	T	A	7: 88,099,749 (GRCm39)	I88N	probably damaging	Het
Rbfox2	A	G	15: 76,976,057 (GRCm39)		probably benign	Het
Samd5	A	G	10: 9,550,683 (GRCm39)	W9R	probably damaging	Het
Sec14l1	A	T	11: 117,047,233 (GRCm39)	K637I	possibly damaging	Het
Sh2b1	A	T	7: 126,070,620 (GRCm39)	D360E	possibly damaging	Het
Sh3bp4	A	G	1: 89,073,036 (GRCm39)	N628S	possibly damaging	Het
Sim1	A	T	10: 50,784,057 (GRCm39)	I104F	probably damaging	Het
Smcp	T	A	3: 92,491,827 (GRCm39)	T7S	unknown	Het
Sp4	A	G	12: 118,264,551 (GRCm39)		probably benign	Het
Tectb	G	T	19: 55,170,393 (GRCm39)	K81N	probably damaging	Het
Thbs4	G	T	13: 92,890,918 (GRCm39)	H850N	probably benign	Het
Tiam1	T	C	16: 89,694,642 (GRCm39)	M272V	probably benign	Het
Trav13-3	T	A	14: 53,967,233 (GRCm39)		noncoding transcript	Het
Ubap2l	A	T	3: 89,928,680 (GRCm39)	S478T	possibly damaging	Het
Vmn2r85	A	G	10: 130,255,054 (GRCm39)		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
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
R7126:Mthfd2	UTSW	6	83,290,472 (GRCm39)	missense	probably benign	0.02
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

Posted On

2013-07-24