Incidental Mutation 'R8943:Mthfd1l'
ID 681105
Institutional Source Beutler Lab
Gene Symbol Mthfd1l
Ensembl Gene ENSMUSG00000040675
Gene Name methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like
Synonyms 2410004L15Rik, Fthfsdc1
MMRRC Submission 068782-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R8943 (G1)
Quality Score 225.009
Status Validated
Chromosome 10
Chromosomal Location 3923118-4117081 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 3978466 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Leucine at position 442 (H442L)
Ref Sequence ENSEMBL: ENSMUSP00000112897 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000043735] [ENSMUST00000117291] [ENSMUST00000120585]
AlphaFold Q3V3R1
Predicted Effect probably damaging
Transcript: ENSMUST00000043735
AA Change: H442L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000036178
Gene: ENSMUSG00000040675
AA Change: H442L

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
low complexity region 30 41 N/A INTRINSIC
Pfam:THF_DHG_CYH 71 179 2.9e-15 PFAM
Pfam:THF_DHG_CYH_C 182 337 1.1e-27 PFAM
Pfam:FTHFS 358 977 1.2e-260 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000117291
AA Change: H442L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000112870
Gene: ENSMUSG00000040675
AA Change: H442L

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
low complexity region 30 41 N/A INTRINSIC
Pfam:THF_DHG_CYH 71 179 2.9e-15 PFAM
Pfam:THF_DHG_CYH_C 182 337 1.1e-27 PFAM
Pfam:FTHFS 358 977 1.2e-260 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000120585
AA Change: H442L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000112897
Gene: ENSMUSG00000040675
AA Change: H442L

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
low complexity region 30 41 N/A INTRINSIC
Pfam:THF_DHG_CYH 70 179 8e-17 PFAM
Pfam:THF_DHG_CYH_C 182 337 5.4e-28 PFAM
Pfam:FTHFS 359 977 7.2e-260 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.5%
Validation Efficiency 98% (50/51)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]
PHENOTYPE: Homozygous deletion of this gene causes embryonic lethality, delayed embryonic growth, craniofacial anomalies, and neural tube defects including craniorachischisis, exencephaly and/or a wavy neural tube. Maternal formate supplementation reduces the incidence of NTDs and improves embryonic growth. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2610021A01Rik T C 7: 41,275,667 (GRCm39) S457P probably damaging Het
Aak1 A G 6: 86,964,234 (GRCm39) N945S unknown Het
Actr1a C A 19: 46,369,438 (GRCm39) R192L possibly damaging Het
Adgrl2 T A 3: 148,534,119 (GRCm39) N1036I probably damaging Het
Ak5 A G 3: 152,361,511 (GRCm39) V137A probably damaging Het
Aldh1a2 T C 9: 71,169,055 (GRCm39) V179A probably damaging Het
Ap2b1 A T 11: 83,237,579 (GRCm39) I548F probably damaging Het
Arhgef10l A G 4: 140,292,550 (GRCm39) Y352H probably damaging Het
Atad5 C T 11: 79,986,524 (GRCm39) T537M possibly damaging Het
Atoh7 A G 10: 62,935,938 (GRCm39) K2E possibly damaging Het
BC061237 A G 14: 44,741,658 (GRCm39) I134V probably benign Het
Cadm1 T C 9: 47,701,136 (GRCm39) I141T probably damaging Het
Capn10 T C 1: 92,871,454 (GRCm39) S351P probably damaging Het
Cct6b T C 11: 82,654,959 (GRCm39) probably benign Het
Cd19 T C 7: 126,011,330 (GRCm39) T284A probably benign Het
Cfap53 A G 18: 74,432,253 (GRCm39) Y47C probably damaging Het
Cldn18 T C 9: 99,578,162 (GRCm39) M194V probably benign Het
Dgkb T A 12: 38,652,777 (GRCm39) Y721N probably damaging Het
Dmbt1 A G 7: 130,721,372 (GRCm39) Q1880R possibly damaging Het
Dock2 T C 11: 34,599,646 (GRCm39) N311S possibly damaging Het
Dpysl5 G T 5: 30,935,375 (GRCm39) M159I probably benign Het
Eif2b3 G A 4: 116,901,778 (GRCm39) G147E probably damaging Het
Fam193a A G 5: 34,597,796 (GRCm39) D531G probably benign Het
Fndc3b T C 3: 27,555,329 (GRCm39) probably benign Het
Foxe3 C A 4: 114,782,523 (GRCm39) A230S unknown Het
Gm5591 A T 7: 38,219,727 (GRCm39) V382E probably benign Het
Gm7995 A T 14: 42,132,228 (GRCm39) N21I probably damaging Het
Ipo8 G A 6: 148,676,547 (GRCm39) P981S probably benign Het
Kcnh8 A G 17: 53,104,486 (GRCm39) D161G probably benign Het
Krt71 A G 15: 101,645,180 (GRCm39) I377T possibly damaging Het
Krt75 A T 15: 101,476,767 (GRCm39) M374K probably benign Het
Krt9 TCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCC TCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCC 11: 100,079,903 (GRCm39) probably benign Het
Lpcat1 A G 13: 73,662,029 (GRCm39) T409A probably benign Het
Lrch1 A T 14: 75,032,808 (GRCm39) I514K probably benign Het
Mc4r A C 18: 66,993,110 (GRCm39) M1R probably null Het
Or5d38 T A 2: 87,954,718 (GRCm39) I204F probably damaging Het
Pdcd1lg2 T C 19: 29,423,553 (GRCm39) M199T probably benign Het
Pigg G A 5: 108,484,066 (GRCm39) V438M probably damaging Het
Pira12 T C 7: 3,898,365 (GRCm39) E319G probably benign Het
Ppfibp1 T A 6: 146,920,681 (GRCm39) probably null Het
Rbm15 T A 3: 107,239,372 (GRCm39) Y342F possibly damaging Het
Rhbdl1 A T 17: 26,054,116 (GRCm39) V278E probably damaging Het
Ryr3 T C 2: 112,465,669 (GRCm39) N4781S probably damaging Het
Scn7a A T 2: 66,525,206 (GRCm39) silent Het
Sfswap A G 5: 129,581,168 (GRCm39) R114G probably damaging Het
Sohlh2 C A 3: 55,104,282 (GRCm39) A258D possibly damaging Het
Sstr4 T A 2: 148,237,782 (GRCm39) V131D possibly damaging Het
Tenm2 T C 11: 36,834,861 (GRCm39) T45A probably damaging Het
Tmem131l A T 3: 83,831,479 (GRCm39) F818I probably damaging Het
Trappc6b A G 12: 59,097,149 (GRCm39) F58L probably damaging Het
Vmn1r229 A T 17: 21,035,418 (GRCm39) H221L possibly damaging Het
Vmn1r33 T A 6: 66,588,783 (GRCm39) Y257F probably damaging Het
Wdfy3 T C 5: 101,993,231 (GRCm39) probably benign Het
Zfp446 C T 7: 12,713,564 (GRCm39) Q177* probably null Het
Zup1 A G 10: 33,795,301 (GRCm39) *552Q probably null Het
Other mutations in Mthfd1l
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00932:Mthfd1l APN 10 3,989,971 (GRCm38) synonymous probably benign
IGL01013:Mthfd1l APN 10 3,980,716 (GRCm39) missense probably damaging 1.00
IGL01018:Mthfd1l APN 10 3,982,345 (GRCm39) splice site probably benign
IGL01018:Mthfd1l APN 10 3,928,708 (GRCm39) missense probably benign
IGL01018:Mthfd1l APN 10 3,957,800 (GRCm39) missense probably benign
IGL01068:Mthfd1l APN 10 3,978,428 (GRCm39) missense probably damaging 1.00
IGL01584:Mthfd1l APN 10 3,966,738 (GRCm39) missense probably damaging 0.97
IGL01609:Mthfd1l APN 10 3,968,567 (GRCm39) missense probably benign 0.00
IGL02272:Mthfd1l APN 10 3,991,812 (GRCm39) missense probably damaging 0.99
IGL02344:Mthfd1l APN 10 3,998,272 (GRCm39) splice site probably null
IGL02429:Mthfd1l APN 10 4,039,334 (GRCm39) missense probably damaging 1.00
IGL02503:Mthfd1l APN 10 4,033,824 (GRCm39) missense probably damaging 1.00
IGL02748:Mthfd1l APN 10 3,930,268 (GRCm39) critical splice donor site probably null
IGL02748:Mthfd1l APN 10 3,968,587 (GRCm39) missense possibly damaging 0.94
IGL03031:Mthfd1l APN 10 3,968,601 (GRCm39) critical splice donor site probably null
IGL03047:Mthfd1l APN 10 3,930,409 (GRCm39) splice site probably benign
IGL03215:Mthfd1l APN 10 3,991,826 (GRCm39) missense probably benign 0.14
IGL03367:Mthfd1l APN 10 4,056,536 (GRCm39) splice site probably benign
R0047:Mthfd1l UTSW 10 3,928,727 (GRCm39) splice site probably benign
R0047:Mthfd1l UTSW 10 3,928,727 (GRCm39) splice site probably benign
R0107:Mthfd1l UTSW 10 3,991,838 (GRCm39) missense probably benign
R0348:Mthfd1l UTSW 10 4,006,766 (GRCm39) missense probably damaging 1.00
R0496:Mthfd1l UTSW 10 4,040,006 (GRCm39) missense probably benign
R0658:Mthfd1l UTSW 10 3,997,976 (GRCm39) splice site probably null
R1177:Mthfd1l UTSW 10 3,935,661 (GRCm39) missense possibly damaging 0.82
R1676:Mthfd1l UTSW 10 4,033,877 (GRCm39) critical splice donor site probably null
R1703:Mthfd1l UTSW 10 4,098,093 (GRCm39) missense probably damaging 1.00
R1888:Mthfd1l UTSW 10 4,056,528 (GRCm39) missense probably damaging 1.00
R1888:Mthfd1l UTSW 10 4,056,528 (GRCm39) missense probably damaging 1.00
R1891:Mthfd1l UTSW 10 3,982,284 (GRCm39) nonsense probably null
R2014:Mthfd1l UTSW 10 3,997,894 (GRCm39) missense probably benign
R2061:Mthfd1l UTSW 10 4,053,288 (GRCm39) missense probably benign 0.00
R2197:Mthfd1l UTSW 10 3,978,399 (GRCm39) missense probably damaging 1.00
R2360:Mthfd1l UTSW 10 4,006,771 (GRCm39) missense probably damaging 1.00
R3085:Mthfd1l UTSW 10 4,040,007 (GRCm39) missense probably benign 0.00
R3176:Mthfd1l UTSW 10 4,098,025 (GRCm39) missense probably damaging 1.00
R3276:Mthfd1l UTSW 10 4,098,025 (GRCm39) missense probably damaging 1.00
R4065:Mthfd1l UTSW 10 3,982,242 (GRCm39) missense probably damaging 1.00
R4612:Mthfd1l UTSW 10 3,980,717 (GRCm39) missense probably damaging 1.00
R4803:Mthfd1l UTSW 10 3,957,840 (GRCm39) missense possibly damaging 0.52
R4883:Mthfd1l UTSW 10 3,957,775 (GRCm39) missense probably benign 0.11
R4932:Mthfd1l UTSW 10 3,930,241 (GRCm39) missense probably benign 0.00
R5507:Mthfd1l UTSW 10 4,056,432 (GRCm39) missense probably benign 0.20
R5687:Mthfd1l UTSW 10 3,940,002 (GRCm39) splice site probably null
R5694:Mthfd1l UTSW 10 3,985,239 (GRCm39) missense possibly damaging 0.90
R5727:Mthfd1l UTSW 10 4,053,302 (GRCm39) missense possibly damaging 0.86
R5908:Mthfd1l UTSW 10 4,039,392 (GRCm39) missense probably damaging 1.00
R5951:Mthfd1l UTSW 10 3,998,222 (GRCm39) missense probably damaging 1.00
R6330:Mthfd1l UTSW 10 3,930,234 (GRCm39) missense probably benign
R6583:Mthfd1l UTSW 10 3,997,937 (GRCm39) missense probably damaging 0.96
R6846:Mthfd1l UTSW 10 3,997,898 (GRCm39) missense probably damaging 1.00
R7105:Mthfd1l UTSW 10 4,053,261 (GRCm39) missense probably benign
R7456:Mthfd1l UTSW 10 4,039,998 (GRCm39) missense probably damaging 1.00
R7848:Mthfd1l UTSW 10 4,033,739 (GRCm39) missense possibly damaging 0.81
R8003:Mthfd1l UTSW 10 3,934,147 (GRCm39) missense probably benign 0.00
R8073:Mthfd1l UTSW 10 3,923,417 (GRCm39) missense probably benign 0.28
R8140:Mthfd1l UTSW 10 3,957,745 (GRCm39) nonsense probably null
R8478:Mthfd1l UTSW 10 4,098,064 (GRCm39) missense probably damaging 1.00
R8677:Mthfd1l UTSW 10 3,998,250 (GRCm39) missense possibly damaging 0.58
R9086:Mthfd1l UTSW 10 3,923,412 (GRCm39) missense probably benign 0.22
R9267:Mthfd1l UTSW 10 3,934,154 (GRCm39) missense probably benign
R9371:Mthfd1l UTSW 10 4,053,335 (GRCm39) missense possibly damaging 0.49
X0003:Mthfd1l UTSW 10 4,039,303 (GRCm39) missense probably damaging 0.99
Z1088:Mthfd1l UTSW 10 3,957,844 (GRCm39) missense probably benign 0.00
Predicted Primers PCR Primer
(F):5'- TGTGCTATACCTGGGAACACTC -3'
(R):5'- ACCCAGCTCTTTTGCAAAGC -3'

Sequencing Primer
(F):5'- TACATTGGGAGAACGCTGCTC -3'
(R):5'- CCAGCTCTTTTGCAAAGCATTTAAC -3'
Posted On 2021-08-31