Incidental Mutation 'R4473:Mthfd2'
ID 330457
Institutional Source Beutler Lab
Gene Symbol Mthfd2
Ensembl Gene ENSMUSG00000005667
Gene Name methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase
Synonyms NMDMC
MMRRC Submission 041730-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4473 (G1)
Quality Score 158
Status Validated
Chromosome 6
Chromosomal Location 83282673-83302890 bp(-) (GRCm39)
Type of Mutation unclassified
DNA Base Change (assembly) A to G at 83287517 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000145222 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005810] [ENSMUST00000203847] [ENSMUST00000204472]
AlphaFold P18155
Predicted Effect probably benign
Transcript: ENSMUST00000005810
SMART Domains Protein: ENSMUSP00000005810
Gene: ENSMUSG00000005667

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 0.0898 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 97.1%
  • 20x: 94.9%
Validation Efficiency 100% (36/36)
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: 31 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acot7 C A 4: 152,291,313 (GRCm39) T93K probably damaging Het
Actg1 G A 11: 120,239,085 (GRCm39) R2C probably benign Het
Alb T C 5: 90,611,912 (GRCm39) C114R probably damaging Het
Alpk1 T C 3: 127,473,667 (GRCm39) T779A probably damaging Het
Atp2a2 A T 5: 122,595,327 (GRCm39) S1008T probably benign Het
Corin T C 5: 72,496,400 (GRCm39) S510G probably damaging Het
D630003M21Rik G A 2: 158,055,382 (GRCm39) P585L probably damaging Het
Eddm3b A G 14: 51,354,236 (GRCm39) T75A probably benign Het
Elavl2 T C 4: 91,149,246 (GRCm39) probably null Het
Erc1 G T 6: 119,825,417 (GRCm39) probably null Het
Fancf A G 7: 51,511,948 (GRCm39) C19R probably benign Het
Fastkd2 T C 1: 63,770,833 (GRCm39) L63P probably damaging Het
Fmo1 A G 1: 162,677,732 (GRCm39) V128A possibly damaging Het
Ifnar1 T C 16: 91,292,058 (GRCm39) V133A probably damaging Het
Ighv1-49 A T 12: 115,018,959 (GRCm39) Y79N probably damaging Het
Klhl23 A G 2: 69,654,151 (GRCm39) E7G possibly damaging Het
Or5d35 T A 2: 87,855,464 (GRCm39) Y133N probably damaging Het
Parn A G 16: 13,482,549 (GRCm39) S100P probably benign Het
Podnl1 A T 8: 84,858,614 (GRCm39) I505F possibly damaging Het
Ppp6r3 G T 19: 3,561,978 (GRCm39) Q228K probably damaging Het
Pramel38 A G 5: 94,366,029 (GRCm39) N49S probably benign Het
Rab22a C T 2: 173,537,056 (GRCm39) T85M probably damaging Het
Siah1b G A X: 162,854,688 (GRCm39) P131S probably damaging Het
Skor2 C T 18: 76,947,156 (GRCm39) P293S unknown Het
Sox18 T C 2: 181,312,669 (GRCm39) K154R probably damaging Het
Tfpi A T 2: 84,288,426 (GRCm39) L10Q probably null Het
Trim66 A T 7: 109,081,202 (GRCm39) I239N probably damaging Het
Ttll1 T A 15: 83,376,810 (GRCm39) K304N probably damaging Het
Vmn1r5 G A 6: 56,962,633 (GRCm39) V103I probably benign Het
Vnn1 T C 10: 23,770,789 (GRCm39) W6R probably benign Het
Wdr35 A G 12: 9,065,995 (GRCm39) Y651C 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
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 PCR Primer
(F):5'- GTCACAGGATGGCTTTTGAGAG -3'
(R):5'- TTGGATTTGTGACCCAGGTC -3'

Sequencing Primer
(F):5'- ACAGGATGGCTTTTGAGAGTTATCAC -3'
(R):5'- TCTGATACACATTCTAAGACAGAGC -3'
Posted On 2015-07-21