Incidental Mutation 'R7602:Mthfd2'
ID 588055
Institutional Source Beutler Lab
Gene Symbol Mthfd2
Ensembl Gene ENSMUSG00000005667
Gene Name methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase
Synonyms NMDMC
MMRRC Submission 045674-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7602 (G1)
Quality Score 225.009
Status Validated
Chromosome 6
Chromosomal Location 83282673-83302890 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 83288830 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Aspartic acid at position 125 (N125D)
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: N125D

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)
SMART Domains Protein: ENSMUSP00000005810
Gene: ENSMUSG00000005667
AA Change: N125D

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 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 0.0710 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.2%
Validation Efficiency 100% (58/58)
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: 59 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700025G04Rik A T 1: 151,856,266 (GRCm39) Y34N probably damaging Het
A2m T C 6: 121,618,966 (GRCm39) V237A probably damaging Het
A2m A T 6: 121,647,895 (GRCm39) D1129V possibly damaging Het
Aadacl2fm3 T C 3: 59,784,697 (GRCm39) I390T probably benign Het
Abca7 A G 10: 79,833,846 (GRCm39) probably null Het
Adam34l C T 8: 44,079,703 (GRCm39) G174R probably damaging Het
Ap3m2 T C 8: 23,282,770 (GRCm39) N256S probably benign Het
Atr C T 9: 95,789,436 (GRCm39) H1531Y possibly damaging Het
Carmil3 C T 14: 55,738,965 (GRCm39) A873V probably null Het
Casp8 A C 1: 58,872,898 (GRCm39) K258T probably benign Het
Cast A G 13: 74,885,084 (GRCm39) S222P probably benign Het
Cpsf7 C T 19: 10,512,737 (GRCm39) P274S probably damaging Het
Ddx24 A T 12: 103,382,519 (GRCm39) L688* probably null Het
Ddx59 A G 1: 136,361,559 (GRCm39) I475V probably benign Het
Dhx29 T A 13: 113,081,093 (GRCm39) S376T possibly damaging Het
Dhx57 G T 17: 80,582,290 (GRCm39) N438K probably benign Het
Dlk1 T A 12: 109,421,551 (GRCm39) probably null Het
Efcab15 T C 11: 103,091,004 (GRCm39) M114V probably benign Het
Epha6 T C 16: 59,595,931 (GRCm39) D920G probably damaging Het
Exo5 A T 4: 120,778,818 (GRCm39) V349E probably benign Het
Fam234b T C 6: 135,202,241 (GRCm39) V321A possibly damaging Het
Gbp3 A G 3: 142,274,822 (GRCm39) E383G probably benign Het
Gga2 T C 7: 121,596,553 (GRCm39) N408S probably benign Het
Gse1 T C 8: 121,296,043 (GRCm39) V532A unknown Het
Hnrnpul2 T C 19: 8,808,673 (GRCm39) Y712H probably damaging Het
Hpca T C 4: 129,014,019 (GRCm39) probably benign Het
Ifitm3 A G 7: 140,590,372 (GRCm39) F63L probably damaging Het
Inava G T 1: 136,153,135 (GRCm39) C252* probably null Het
Kank1 A T 19: 25,399,525 (GRCm39) T940S probably benign Het
Klhl9 C A 4: 88,640,646 (GRCm39) probably benign Het
Krt36 T C 11: 99,993,786 (GRCm39) M351V probably benign Het
Muc4 C G 16: 32,575,221 (GRCm39) Q1269E probably benign Het
Ncoa2 A G 1: 13,247,350 (GRCm39) S358P possibly damaging Het
Nmnat1 T C 4: 149,557,808 (GRCm39) H78R probably benign Het
Or10s1 T G 9: 39,986,455 (GRCm39) L288R probably damaging Het
Or5k1 T C 16: 58,617,343 (GRCm39) I289V possibly damaging Het
Or5m13b A T 2: 85,754,146 (GRCm39) Y178F probably damaging Het
Or9r3 A G 10: 129,948,179 (GRCm39) M160T probably benign Het
Pabpc4 A T 4: 123,186,685 (GRCm39) D302V possibly damaging Het
Pgap1 A T 1: 54,582,345 (GRCm39) S167R probably damaging Het
Phf12 T C 11: 77,914,109 (GRCm39) L517P probably benign Het
Rcan2 A G 17: 44,328,689 (GRCm39) D86G probably benign Het
Ryk T C 9: 102,775,715 (GRCm39) Y442H probably damaging Het
Scfd2 G T 5: 74,623,271 (GRCm39) Q421K probably benign Het
Sirpa G T 2: 129,451,072 (GRCm39) V111F probably damaging Het
Skint4 A T 4: 111,975,468 (GRCm39) T143S possibly damaging Het
Slc12a8 C A 16: 33,445,494 (GRCm39) H463N probably benign Het
Sp110 G A 1: 85,506,813 (GRCm39) R417C probably benign Het
Sptlc2 A G 12: 87,388,463 (GRCm39) Y340H probably damaging Het
Ssc5d T A 7: 4,945,745 (GRCm39) W926R possibly damaging Het
Tgfa A G 6: 86,246,944 (GRCm39) E82G probably damaging Het
Thrsp A G 7: 97,066,514 (GRCm39) I66T probably damaging Het
Ttn T C 2: 76,681,988 (GRCm39) E1003G unknown Het
Tube1 A T 10: 39,018,262 (GRCm39) H113L probably benign Het
Uri1 A G 7: 37,681,053 (GRCm39) V117A probably benign Het
Ush2a G A 1: 188,380,606 (GRCm39) C2305Y probably damaging Het
Zbtb7a T G 10: 80,980,010 (GRCm39) V68G probably damaging Het
Zfr T A 15: 12,159,763 (GRCm39) D686E possibly damaging Het
Zscan4f G A 7: 11,135,308 (GRCm39) S238N possibly damaging 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
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
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'- CTTTAAGCACTTCAAACAGTACCTC -3'
(R):5'- TACACCCTGGGCAGTCACTTAG -3'

Sequencing Primer
(F):5'- tgtgATGGGTGTTTTGCC -3'
(R):5'- TTTTCCCCCAGAGAAGAACTTAGTC -3'
Posted On 2019-10-24