Incidental Mutation 'PIT4480001:Mdh1'
ID 554874
Institutional Source Beutler Lab
Gene Symbol Mdh1
Ensembl Gene ENSMUSG00000020321
Gene Name malate dehydrogenase 1, NAD (soluble)
Synonyms Mor-2, B230377B03Rik, MDH-s, Mor2
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # PIT4480001 (G1)
Quality Score 225.009
Status Not validated
Chromosome 11
Chromosomal Location 21506692-21521934 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 21508538 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Leucine at position 268 (S268L)
Ref Sequence ENSEMBL: ENSMUSP00000099938 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000102874] [ENSMUST00000125302]
AlphaFold P14152
Predicted Effect probably damaging
Transcript: ENSMUST00000102874
AA Change: S268L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000099938
Gene: ENSMUSG00000020321
AA Change: S268L

DomainStartEndE-ValueType
Pfam:Ldh_1_N 5 153 7.3e-41 PFAM
Pfam:Ldh_1_C 156 331 1.2e-47 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000125302
SMART Domains Protein: ENSMUSP00000119816
Gene: ENSMUSG00000020321

DomainStartEndE-ValueType
Pfam:Ldh_1_N 5 153 5e-42 PFAM
Coding Region Coverage
  • 1x: 93.3%
  • 3x: 90.7%
  • 10x: 83.8%
  • 20x: 69.1%
Validation Efficiency
MGI Phenotype FUNCTION: This gene encodes an enzyme that catalyzes the NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate in many metabolic pathways, including the citric acid cycle. Two main isozymes are known to exist in eukaryotic cells: one is found in the mitochondrial matrix and the other in the cytoplasm. This gene encodes the cytosolic isozyme, which plays a key role in the malate-aspartate shuttle that allows malate to pass through the mitochondrial membrane to be transformed into oxaloacetate for further cellular processes. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. A pseudogene has been identified on chromosomes 12. [provided by RefSeq, Feb 2016]
PHENOTYPE: An ENU-induced mutation results in prenatal lethality in homozygotes and decreased enzyme activity in heterozygotes. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 58 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Actn3 G A 19: 4,917,605 (GRCm39) Q413* probably null Het
Ahnak2 C T 12: 112,740,358 (GRCm39) S1238N possibly damaging Het
Arsk T C 13: 76,210,484 (GRCm39) E521G probably damaging Het
Baiap2 A G 11: 119,887,913 (GRCm39) T356A probably benign Het
Baz1b G A 5: 135,246,819 (GRCm39) R756H probably damaging Het
Celsr1 G A 15: 85,916,615 (GRCm39) P453S probably damaging Het
Cep41 G A 6: 30,658,412 (GRCm39) P196S probably damaging Het
Cln5 T A 14: 103,309,214 (GRCm39) Y89* probably null Het
Cntnap3 A G 13: 64,905,024 (GRCm39) F919S probably damaging Het
Cntrl C T 2: 35,045,440 (GRCm39) H1383Y probably damaging Het
Cobl A G 11: 12,203,592 (GRCm39) S1037P probably benign Het
Col17a1 A T 19: 47,659,813 (GRCm39) S380T probably benign Het
Cyrib G A 15: 63,828,490 (GRCm39) T11I probably benign Het
Dagla A T 19: 10,238,022 (GRCm39) S323T probably benign Het
Dicer1 G T 12: 104,662,803 (GRCm39) Q1593K probably benign Het
Dnah6 T C 6: 73,078,863 (GRCm39) I2367V probably benign Het
Emc1 T C 4: 139,086,588 (GRCm39) S184P possibly damaging Het
Eps8l1 G A 7: 4,474,414 (GRCm39) S295N probably benign Het
Erbb4 A T 1: 68,114,702 (GRCm39) M914K probably damaging Het
Eva1a A G 6: 82,068,784 (GRCm39) E37G probably damaging Het
Fyco1 G T 9: 123,657,715 (GRCm39) Y820* probably null Het
Gipr T C 7: 18,896,859 (GRCm39) Y137C probably damaging Het
Gm5414 A G 15: 101,536,181 (GRCm39) V148A probably damaging Het
Gpn1 T C 5: 31,654,685 (GRCm39) V79A probably damaging Het
Grk2 G A 19: 4,337,437 (GRCm39) R617C possibly damaging Het
Inpp4b A C 8: 82,772,896 (GRCm39) E730A probably damaging Het
Inpp5f C T 7: 128,286,858 (GRCm39) T579I probably benign Het
Kif15 A T 9: 122,840,608 (GRCm39) M1201L probably benign Het
Ltbp3 A G 19: 5,801,254 (GRCm39) N631S possibly damaging Het
Mgat4e T A 1: 134,469,103 (GRCm39) T314S possibly damaging Het
Nsd1 A G 13: 55,361,731 (GRCm39) Q233R probably benign Het
Or11g1 T C 14: 50,651,372 (GRCm39) F124L probably benign Het
Or5w17 T C 2: 87,584,127 (GRCm39) D70G possibly damaging Het
Paqr5 T A 9: 61,863,438 (GRCm39) I295L probably benign Het
Peg10 C T 6: 4,756,560 (GRCm39) H379Y unknown Het
Phtf2 A T 5: 21,018,242 (GRCm39) I33N probably damaging Het
Plcb2 T C 2: 118,553,977 (GRCm39) M115V probably benign Het
Ppp2r3d A G 9: 101,003,576 (GRCm39) Y431H possibly damaging Het
Prph2 GT G 17: 47,222,039 (GRCm39) probably null Het
Psmd1 C T 1: 86,055,960 (GRCm39) P774L probably damaging Het
Ranbp17 A T 11: 33,247,340 (GRCm39) probably null Het
Rptn A G 3: 93,304,977 (GRCm39) D770G possibly damaging Het
Serac1 A G 17: 6,101,087 (GRCm39) L439P probably damaging Het
Slitrk6 TTTTAGTCTGTTCTACCAACACCTT TTT 14: 110,987,257 (GRCm39) probably null Het
Sox6 T C 7: 115,196,744 (GRCm39) I295M probably benign Het
Spata31h1 T C 10: 82,119,586 (GRCm39) M4475V probably benign Het
Sulf1 T A 1: 12,929,637 (GRCm39) D301E probably benign Het
Tas2r117 G A 6: 132,780,014 (GRCm39) V51I possibly damaging Het
Tbx2 C T 11: 85,725,561 (GRCm39) R171C probably damaging Het
Tgfbr1 A G 4: 47,402,955 (GRCm39) I320V probably benign Het
Tjp3 C A 10: 81,115,091 (GRCm39) G396W probably damaging Het
Tmprss2 T C 16: 97,400,460 (GRCm39) N4D possibly damaging Het
Tnfaip3 T C 10: 18,883,071 (GRCm39) N165D probably benign Het
Tnfrsf21 A T 17: 43,348,802 (GRCm39) Y138F probably benign Het
Utp4 T C 8: 107,632,817 (GRCm39) S267P probably benign Het
Wnk1 A T 6: 119,940,328 (GRCm39) L803* probably null Het
Zbbx T A 3: 75,043,794 (GRCm39) D35V probably damaging Het
Zscan12 T G 13: 21,552,744 (GRCm39) N189K possibly damaging Het
Other mutations in Mdh1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02171:Mdh1 APN 11 21,507,438 (GRCm39) utr 3 prime probably benign
IGL02273:Mdh1 APN 11 21,509,786 (GRCm39) missense probably benign 0.38
IGL03198:Mdh1 APN 11 21,514,168 (GRCm39) missense probably damaging 1.00
R0771:Mdh1 UTSW 11 21,507,550 (GRCm39) missense probably benign 0.27
R1016:Mdh1 UTSW 11 21,509,769 (GRCm39) missense probably benign 0.01
R3854:Mdh1 UTSW 11 21,509,281 (GRCm39) missense probably benign 0.31
R3855:Mdh1 UTSW 11 21,509,281 (GRCm39) missense probably benign 0.31
R3886:Mdh1 UTSW 11 21,509,832 (GRCm39) missense probably damaging 0.97
R4474:Mdh1 UTSW 11 21,516,624 (GRCm39) missense possibly damaging 0.49
R4507:Mdh1 UTSW 11 21,508,470 (GRCm39) missense probably benign 0.01
R4724:Mdh1 UTSW 11 21,512,957 (GRCm39) missense probably damaging 1.00
R4986:Mdh1 UTSW 11 21,508,545 (GRCm39) missense possibly damaging 0.85
R5472:Mdh1 UTSW 11 21,509,786 (GRCm39) missense probably benign 0.38
R7088:Mdh1 UTSW 11 21,508,484 (GRCm39) missense probably damaging 1.00
R8427:Mdh1 UTSW 11 21,514,138 (GRCm39) missense probably benign 0.00
R9717:Mdh1 UTSW 11 21,521,870 (GRCm39) unclassified probably benign
R9765:Mdh1 UTSW 11 21,512,926 (GRCm39) nonsense probably null
X0063:Mdh1 UTSW 11 21,512,870 (GRCm39) missense possibly damaging 0.92
Predicted Primers PCR Primer
(F):5'- CTTGCTTTCCAGAACAGTTTCAG -3'
(R):5'- CTGGAAGTGTAGATGAAGTGATATCTG -3'

Sequencing Primer
(F):5'- GCTTTCCAGAACAGTTTCAGTATTG -3'
(R):5'- AAGTGATATCTGTGACCCAGTG -3'
Posted On 2019-06-07