Incidental Mutation 'R5301:Mthfd2'
ID 404242
Institutional Source Beutler Lab
Gene Symbol Mthfd2
Ensembl Gene ENSMUSG00000005667
Gene Name methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase
Synonyms NMDMC
MMRRC Submission 042884-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5301 (G1)
Quality Score 225
Status Validated
Chromosome 6
Chromosomal Location 83282673-83302890 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 83287465 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glycine to Valine at position 200 (G200V)
Ref Sequence ENSEMBL: ENSMUSP00000005810 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005810] [ENSMUST00000203847] [ENSMUST00000204472]
AlphaFold P18155
Predicted Effect probably damaging
Transcript: ENSMUST00000005810
AA Change: G200V

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000005810
Gene: ENSMUSG00000005667
AA Change: G200V

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000139802
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141044
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141193
Predicted Effect noncoding transcript
Transcript: ENSMUST00000203375
Predicted Effect noncoding transcript
Transcript: ENSMUST00000203437
Predicted Effect probably benign
Transcript: ENSMUST00000203847
SMART Domains Protein: ENSMUSP00000145266
Gene: ENSMUSG00000005667

DomainStartEndE-ValueType
signal peptide 1 20 N/A INTRINSIC
Pfam:THF_DHG_CYH 39 108 2e-13 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000204472
SMART Domains Protein: ENSMUSP00000145222
Gene: ENSMUSG00000005667

DomainStartEndE-ValueType
Pfam:THF_DHG_CYH 20 97 2.2e-20 PFAM
Meta Mutation Damage Score 0.9744 question?
Coding Region Coverage
  • 1x: 99.4%
  • 3x: 98.8%
  • 10x: 97.7%
  • 20x: 96.3%
Validation Efficiency 93% (52/56)
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: 53 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca4 T C 3: 121,896,502 (GRCm39) V578A probably damaging Het
Abcb11 T C 2: 69,117,191 (GRCm39) I486V probably damaging Het
Abcc9 G A 6: 142,536,207 (GRCm39) T1509I probably benign Het
Akr1c20 T A 13: 4,573,279 (GRCm39) D12V probably damaging Het
Asb1 A G 1: 91,482,475 (GRCm39) Y66C probably damaging Het
Atg14 G A 14: 47,805,656 (GRCm39) R70C probably damaging Het
Bcl10 A G 3: 145,636,342 (GRCm39) D80G probably damaging Het
Bdnf T C 2: 109,553,884 (GRCm39) V46A probably benign Het
Cyp11a1 A G 9: 57,926,544 (GRCm39) probably benign Het
Cyp3a44 A G 5: 145,725,326 (GRCm39) S292P probably damaging Het
Desi2 A G 1: 178,071,952 (GRCm39) I85M probably benign Het
Dnah2 C T 11: 69,349,746 (GRCm39) R2399Q probably benign Het
Dock10 T C 1: 80,625,973 (GRCm39) D49G probably benign Het
Epcam T A 17: 87,944,305 (GRCm39) L20Q possibly damaging Het
Ercc4 T C 16: 12,948,550 (GRCm39) V589A probably damaging Het
Fcgbp A T 7: 27,793,099 (GRCm39) K1034N possibly damaging Het
Fras1 C T 5: 96,805,125 (GRCm39) L1256F possibly damaging Het
Gata5 T C 2: 179,975,786 (GRCm39) Y126C probably damaging Het
Gja1 T C 10: 56,264,475 (GRCm39) L278P probably damaging Het
Gm11596 C A 11: 99,683,847 (GRCm39) R91L unknown Het
Gm29125 A T 1: 80,362,154 (GRCm39) noncoding transcript Het
Hcrtr1 G T 4: 130,031,463 (GRCm39) probably null Het
Ifi207 G A 1: 173,556,977 (GRCm39) S587L possibly damaging Het
Ino80d T C 1: 63,113,578 (GRCm39) T291A probably benign Het
Itgb3 A G 11: 104,524,480 (GRCm39) probably null Het
Kif26b A G 1: 178,358,233 (GRCm39) S115G unknown Het
Klc3 T C 7: 19,130,274 (GRCm39) Y301C probably damaging Het
Klhl18 G C 9: 110,265,195 (GRCm39) N335K possibly damaging Het
Meioc A T 11: 102,570,871 (GRCm39) R867S probably damaging Het
Mplkipl1 C T 19: 61,164,364 (GRCm39) G24R unknown Het
Mroh2a A G 1: 88,186,386 (GRCm39) S64G probably benign Het
Nrap A G 19: 56,367,541 (GRCm39) I312T probably damaging Het
Nrp1 T G 8: 129,160,678 (GRCm39) probably null Het
Obscn A G 11: 59,026,234 (GRCm39) L323P probably damaging Het
Or11g1 T C 14: 50,651,030 (GRCm39) S10P probably benign Het
Or1b1 C T 2: 36,995,210 (GRCm39) V151M probably benign Het
Or9i14 G A 19: 13,792,933 (GRCm39) T7I probably damaging Het
Pkn2 A C 3: 142,544,967 (GRCm39) probably null Het
Ppp1r18 A G 17: 36,179,237 (GRCm39) R371G probably benign Het
Prkar2b A C 12: 32,025,927 (GRCm39) V31G probably damaging Het
Reg3b T A 6: 78,348,243 (GRCm39) M19K probably damaging Het
Sec14l2 G A 11: 4,068,727 (GRCm39) probably benign Het
Sgca C T 11: 94,854,157 (GRCm39) R104Q probably damaging Het
Slc17a6 A G 7: 51,308,519 (GRCm39) Y281C probably damaging Het
Sorcs2 A G 5: 36,196,734 (GRCm39) V637A probably damaging Het
Tdrd9 T A 12: 112,002,963 (GRCm39) probably null Het
Tmem181a T C 17: 6,346,070 (GRCm39) I229T possibly damaging Het
Tmpo A T 10: 90,985,650 (GRCm39) probably benign Het
Ttc41 T C 10: 86,555,384 (GRCm39) V280A probably benign Het
Vmn1r234 G T 17: 21,449,589 (GRCm39) V168F probably benign Het
Vmn2r96 T A 17: 18,817,950 (GRCm39) I701N probably damaging Het
Wnt16 T A 6: 22,297,848 (GRCm39) M238K probably damaging Het
Zfp607b A G 7: 27,403,172 (GRCm39) T543A probably benign Het
Other mutations in Mthfd2
AlleleSourceChrCoordTypePredicted EffectPPH 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
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 PCR Primer
(F):5'- CTCGTTGGGACTGTCTAAGC -3'
(R):5'- AAAGTTCTGTGTAAAGCGTGG -3'

Sequencing Primer
(F):5'- CAGAGACTAGTTCCAGGATCCTTG -3'
(R):5'- TGGTGGTAGGCAACAAGACATTTTC -3'
Posted On 2016-07-22