Incidental Mutation 'R4245:Mthfd1'
ID 320392
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 041061-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4245 (G1)
Quality Score 220
Status Validated
Chromosome 12
Chromosomal Location 76302072-76366577 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 76348047 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 564 (S564P)
Ref Sequence ENSEMBL: ENSMUSP00000021443 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021443] [ENSMUST00000220046]
AlphaFold Q922D8
Predicted Effect probably damaging
Transcript: ENSMUST00000021443
AA Change: S564P

PolyPhen 2 Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000021443
Gene: ENSMUSG00000021048
AA Change: S564P

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000218010
Predicted Effect noncoding transcript
Transcript: ENSMUST00000218331
Predicted Effect noncoding transcript
Transcript: ENSMUST00000218341
Predicted Effect noncoding transcript
Transcript: ENSMUST00000218513
Predicted Effect possibly damaging
Transcript: ENSMUST00000220046
AA Change: S384P

PolyPhen 2 Score 0.936 (Sensitivity: 0.80; Specificity: 0.94)
Meta Mutation Damage Score 0.8267 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.5%
Validation Efficiency 98% (47/48)
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930449A18Rik T A 3: 59,733,203 (GRCm39) noncoding transcript Het
Acacb A T 5: 114,368,845 (GRCm39) T1688S probably damaging Het
Actr1b T C 1: 36,740,911 (GRCm39) Y171C possibly damaging Het
C8a A G 4: 104,733,543 (GRCm39) V4A probably benign Het
Ccdc171 A G 4: 83,473,045 (GRCm39) D158G probably damaging Het
Ccdc184 T A 15: 98,066,750 (GRCm39) probably null Het
Cdc23 T C 18: 34,770,100 (GRCm39) probably benign Het
Dnah5 A G 15: 28,219,335 (GRCm39) N51S probably benign Het
Dock10 T A 1: 80,544,472 (GRCm39) E905V probably benign Het
Eepd1 T C 9: 25,505,920 (GRCm39) I460T probably benign Het
Fen1 T A 19: 10,177,731 (GRCm39) I238F probably damaging Het
Fhdc1 C A 3: 84,352,133 (GRCm39) V1031F probably benign Het
Gm5493 A G 17: 22,966,199 (GRCm39) E28G probably benign Het
Jakmip2 A G 18: 43,710,501 (GRCm39) V234A probably benign Het
Map3k6 T C 4: 132,979,258 (GRCm39) Y1204H possibly damaging Het
Mpeg1 C A 19: 12,440,272 (GRCm39) Q577K probably damaging Het
Mtmr11 T A 3: 96,075,393 (GRCm39) C358S probably damaging Het
Muc4 T C 16: 32,753,802 (GRCm38) I1226T probably benign Het
Myo18b G A 5: 112,840,261 (GRCm39) H2511Y possibly damaging Het
Ndufs6 A T 13: 73,468,512 (GRCm39) D62E probably damaging Het
Or5af2 T C 11: 58,708,604 (GRCm39) Y257H probably damaging Het
Or7e178 T C 9: 20,225,629 (GRCm39) I196V possibly damaging Het
Pcdhga1 T A 18: 37,796,605 (GRCm39) D536E probably damaging Het
Phactr3 G A 2: 177,924,982 (GRCm39) probably null Het
Ptgir A G 7: 16,640,794 (GRCm39) M29V possibly damaging Het
Ptk2 C T 15: 73,103,825 (GRCm39) G749D probably benign Het
Rab3il1 A T 19: 10,007,518 (GRCm39) D222V probably damaging Het
Radil T C 5: 142,529,546 (GRCm39) D50G probably damaging Het
Rfx7 A G 9: 72,499,051 (GRCm39) T72A possibly damaging Het
Scn7a T C 2: 66,572,345 (GRCm39) I209V probably benign Het
Sf3a1 C T 11: 4,117,774 (GRCm39) R179C probably damaging Het
Spata31e2 T C 1: 26,721,161 (GRCm39) N1340D probably benign Het
Styxl2 T C 1: 165,928,685 (GRCm39) E309G probably damaging Het
Tg T C 15: 66,568,318 (GRCm39) V1335A possibly damaging Het
Thnsl1 A G 2: 21,217,059 (GRCm39) E271G probably benign Het
Vill T A 9: 118,900,359 (GRCm39) probably benign Het
Vmn2r79 A G 7: 86,651,624 (GRCm39) D341G possibly damaging Het
Wdr59 T C 8: 112,216,996 (GRCm39) N272D possibly damaging Het
Zar1 T C 5: 72,737,736 (GRCm39) E121G possibly damaging Het
Zfp985 A G 4: 147,667,396 (GRCm39) K88R probably damaging Het
Zscan29 C T 2: 120,995,275 (GRCm39) probably null Het
Other mutations in Mthfd1
AlleleSourceChrCoordTypePredicted EffectPPH 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
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 76,348,102 (GRCm39) missense probably damaging 1.00
R5022:Mthfd1 UTSW 12 76,341,148 (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
R9136:Mthfd1 UTSW 12 76,350,649 (GRCm39) missense probably damaging 0.97
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'- AATGATAGCTCACTGGCCATGC -3'
(R):5'- AATCACTGAAAGACCCCGGG -3'

Sequencing Primer
(F):5'- CCTCCATGAGCTGGGATTATAAGC -3'
(R):5'- CTGAAAGACCCCGGGATGCTAG -3'
Posted On 2015-06-12