Incidental Mutation 'R2026:Dhfr'
ID 220690
Institutional Source Beutler Lab
Gene Symbol Dhfr
Ensembl Gene ENSMUSG00000021707
Gene Name dihydrofolate reductase
Synonyms 8430436I03Rik
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2026 (G1)
Quality Score 225
Status Not validated
Chromosome 13
Chromosomal Location 92491291-92525561 bp(+) (GRCm39)
Type of Mutation nonsense
DNA Base Change (assembly) G to T at 92502279 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glycine to Stop codon at position 117 (G117*)
Ref Sequence ENSEMBL: ENSMUSP00000022218 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000022218]
AlphaFold P00375
PDB Structure Understanding the Role of Leu22 Variants in Methotrexate Resistance: Comparison of Wild-type and Leu22Arg Variant Mouse and Human Dihydrofolate Reductase [X-RAY DIFFRACTION]
New Insights into DHFR Interactions: Analysis of Pneumocystis carinii and Mouse DHFR Complexes with NADPH and Two Highly Potent Trimethoprim Derivatives [X-RAY DIFFRACTION]
Structural Analysis of a Holo Enzyme Complex of Mouse Dihydrofolate Reductase with NADPH and a Ternary Complex wtih the Potent and Selective Inhibitor 2,4-Diamino-6-(2'-hydroxydibenz[b,f]azepin-5-yl)methylpteridine [X-RAY DIFFRACTION]
Structural Analysis of a Holo Enzyme Complex of Mouse Dihydrofolate Reductase with NADPH and a Ternary Complex with the Potent and Selective Inhibitor 2.4-Diamino-6-(-2'-hydroxydibenz[b,f]azepin-5-yl)methylpteridine [X-RAY DIFFRACTION]
Alternate Binding Modes Observed for the E- and Z-isomers of 2,4-Diaminofuro[2,3d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase [X-RAY DIFFRACTION]
Alternate Binding Modes Observed for the E- and Z-Isomers of 2,4-Diaminofuro[2,3-d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase [X-RAY DIFFRACTION]
Predicted Effect probably null
Transcript: ENSMUST00000022218
AA Change: G117*
SMART Domains Protein: ENSMUSP00000022218
Gene: ENSMUSG00000021707
AA Change: G117*

DomainStartEndE-ValueType
Pfam:DHFR_1 4 185 3.9e-37 PFAM
Coding Region Coverage
  • 1x: 99.4%
  • 3x: 98.7%
  • 10x: 97.3%
  • 20x: 95.3%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit lethality soon after E14.5 with reduced size, pallor, impaired hematopoiesis and abnormal folic acid levels. Mice heterozygous for this allele exhibit abnormal folic acid levels, abnormal hemopoiesis and reduced endothelium-dependent vasorelaxation. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 68 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
6430548M08Rik A G 8: 120,880,205 (GRCm39) K269R probably benign Het
Abcc12 A G 8: 87,284,862 (GRCm39) V251A probably benign Het
Avil G A 10: 126,847,742 (GRCm39) G556S probably damaging Het
C3 T C 17: 57,525,562 (GRCm39) Y898C probably damaging Het
Cacng2 A G 15: 77,879,720 (GRCm39) F201L possibly damaging Het
Casp7 T A 19: 56,424,830 (GRCm39) I183N probably damaging Het
Cntn3 A T 6: 102,397,388 (GRCm39) W62R probably damaging Het
Ctrb1 T C 8: 112,415,317 (GRCm39) N119S probably benign Het
Cyp3a59 G A 5: 146,033,098 (GRCm39) V157M probably damaging Het
Dido1 A T 2: 180,330,974 (GRCm39) L158* probably null Het
Dlg2 C A 7: 91,614,931 (GRCm39) P290Q probably damaging Het
Dnah3 T A 7: 119,638,629 (GRCm39) Q1240L probably damaging Het
Exd1 A T 2: 119,350,786 (GRCm39) S492T probably benign Het
Fermt1 T C 2: 132,760,445 (GRCm39) I415M probably benign Het
Fsip2 A G 2: 82,819,788 (GRCm39) T5174A possibly damaging Het
Fuca2 T G 10: 13,388,391 (GRCm39) V389G probably damaging Het
Gm14412 A T 2: 177,008,898 (GRCm39) H50Q possibly damaging Het
Gm5129 G A 5: 29,940,732 (GRCm39) probably benign Het
Hif3a T C 7: 16,778,322 (GRCm39) R437G possibly damaging Het
Hook3 T C 8: 26,528,126 (GRCm39) E588G probably damaging Het
Hs1bp3 A G 12: 8,387,738 (GRCm39) E301G probably benign Het
Icam2 A G 11: 106,273,268 (GRCm39) F15L probably benign Het
Ice2 T C 9: 69,323,607 (GRCm39) S701P probably benign Het
Igf2bp1 A G 11: 95,864,996 (GRCm39) V151A possibly damaging Het
Lig4 A T 8: 10,022,436 (GRCm39) L448Q probably damaging Het
Man2b1 G C 8: 85,821,964 (GRCm39) W726C probably damaging Het
Mepe T C 5: 104,474,957 (GRCm39) S13P possibly damaging Het
Msh6 C T 17: 88,297,771 (GRCm39) H1264Y probably damaging Het
Ncoa1 A T 12: 4,317,647 (GRCm39) S1228R probably benign Het
Ndufa10 A G 1: 92,367,614 (GRCm39) Y339H probably damaging Het
Nup155 A T 15: 8,187,244 (GRCm39) H1391L probably damaging Het
Nutm2 A G 13: 50,628,856 (GRCm39) H640R probably benign Het
Or11i1 T C 3: 106,729,027 (GRCm39) I283V probably benign Het
Or2t1 T C 14: 14,328,891 (GRCm38) V260A probably benign Het
Or51ac3 T A 7: 103,214,084 (GRCm39) Y134F probably damaging Het
Or5b123 T A 19: 13,596,945 (GRCm39) C140S probably damaging Het
Or5w1b G T 2: 87,475,753 (GRCm39) A238E probably damaging Het
Or6c211 T A 10: 129,506,334 (GRCm39) D18V probably damaging Het
Pde1c C T 6: 56,157,175 (GRCm39) V162I probably damaging Het
Pdss2 A T 10: 43,269,871 (GRCm39) N238I possibly damaging Het
Pfas C T 11: 68,884,783 (GRCm39) G473E probably damaging Het
Pkn1 A G 8: 84,398,007 (GRCm39) V795A probably damaging Het
Polq A G 16: 36,883,107 (GRCm39) D1757G possibly damaging Het
Popdc3 T C 10: 45,190,951 (GRCm39) W21R probably damaging Het
Ptch1 T G 13: 63,672,773 (GRCm39) E944A probably benign Het
Ptpro T A 6: 137,420,592 (GRCm39) V1007D probably damaging Het
Pwwp4a G T X: 72,171,261 (GRCm39) G218C probably damaging Het
Rfc1 G T 5: 65,445,372 (GRCm39) T412K probably damaging Het
Sap130 T C 18: 31,831,627 (GRCm39) S706P possibly damaging Het
Scgn T C 13: 24,175,047 (GRCm39) probably benign Het
Smad7 T C 18: 75,527,225 (GRCm39) V357A probably damaging Het
Snrnp48 G T 13: 38,393,862 (GRCm39) A56S possibly damaging Het
Sptbn1 G T 11: 30,054,559 (GRCm39) A2178E probably benign Het
Syn2 C T 6: 115,255,212 (GRCm39) T508I probably benign Het
Tedc2 T A 17: 24,435,291 (GRCm39) E366V probably damaging Het
Tedc2 C A 17: 24,435,292 (GRCm39) E366* probably null Het
Tmtc4 T C 14: 123,158,677 (GRCm39) N682S probably benign Het
Trpm7 T C 2: 126,654,658 (GRCm39) K1427E probably benign Het
Trrap A G 5: 144,739,854 (GRCm39) I1118V possibly damaging Het
Tslp A T 18: 32,948,725 (GRCm39) I37L probably benign Het
Ttll3 G A 6: 113,375,731 (GRCm39) V297M probably damaging Het
Ttn T C 2: 76,540,713 (GRCm39) D34091G possibly damaging Het
Txndc11 CCCGCCGCCGCCGCCGC CCCGCCGCCGCCGC 16: 10,952,338 (GRCm39) probably benign Het
Ube3a T C 7: 58,953,474 (GRCm39) F803L probably damaging Het
Ubn1 A G 16: 4,882,514 (GRCm39) E325G probably damaging Het
Wfikkn2 A G 11: 94,129,779 (GRCm39) W121R possibly damaging Het
Zfp579 C A 7: 4,996,520 (GRCm39) E464* probably null Het
Zfp616 A T 11: 73,974,413 (GRCm39) L227F possibly damaging Het
Other mutations in Dhfr
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01659:Dhfr APN 13 92,492,178 (GRCm39) splice site probably null
R0546:Dhfr UTSW 13 92,504,692 (GRCm39) critical splice acceptor site probably null
R1465:Dhfr UTSW 13 92,504,815 (GRCm39) splice site probably benign
R4905:Dhfr UTSW 13 92,502,282 (GRCm39) missense probably damaging 1.00
R5109:Dhfr UTSW 13 92,491,788 (GRCm39) missense probably damaging 1.00
R7039:Dhfr UTSW 13 92,491,791 (GRCm39) missense probably benign 0.04
R7869:Dhfr UTSW 13 92,494,471 (GRCm39) nonsense probably null
R8905:Dhfr UTSW 13 92,494,467 (GRCm39) missense probably damaging 1.00
R9509:Dhfr UTSW 13 92,504,739 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GTACTAGCTGCTGCCAATTCG -3'
(R):5'- GTACATGAAGTATGATGCACCATC -3'

Sequencing Primer
(F):5'- GCTGCCAATTCGGATTATTTGAC -3'
(R):5'- GCACCATCATAATGTAATACAAGGTC -3'
Posted On 2014-08-25