Incidental Mutation 'R5265:Mlh1'
ID 401667
Institutional Source Beutler Lab
Gene Symbol Mlh1
Ensembl Gene ENSMUSG00000032498
Gene Name mutL homolog 1
Synonyms colon cancer, nonpolyposis type 2, 1110035C23Rik
MMRRC Submission 042833-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R5265 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 111228228-111271791 bp(-) (GRCm38)
Type of Mutation start codon destroyed
DNA Base Change (assembly) A to C at 111271523 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Methionine to Arginine at position 1 (M1R)
Ref Sequence ENSEMBL: ENSMUSP00000035079 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000035079] [ENSMUST00000060711] [ENSMUST00000135218] [ENSMUST00000135807]
AlphaFold Q9JK91
Predicted Effect probably null
Transcript: ENSMUST00000035079
AA Change: M1R

PolyPhen 2 Score 0.933 (Sensitivity: 0.80; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: M1R

HATPase_c 23 158 4.57e-1 SMART
DNA_mis_repair 216 335 1.08e-44 SMART
low complexity region 363 375 N/A INTRINSIC
low complexity region 429 454 N/A INTRINSIC
Pfam:Mlh1_C 504 760 8.3e-100 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000060711
Predicted Effect noncoding transcript
Transcript: ENSMUST00000123869
Predicted Effect noncoding transcript
Transcript: ENSMUST00000134316
Predicted Effect probably null
Transcript: ENSMUST00000135218
AA Change: M1R

PolyPhen 2 Score 0.915 (Sensitivity: 0.81; Specificity: 0.94)
Predicted Effect probably benign
Transcript: ENSMUST00000135807
Predicted Effect noncoding transcript
Transcript: ENSMUST00000200053
Meta Mutation Damage Score 0.9702 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 97.0%
  • 20x: 94.7%
Validation Efficiency 100% (59/59)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+phenotype) found in HNPCC. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described, but their full-length natures have not been determined.[provided by RefSeq, Nov 2009]
PHENOTYPE: Homozygotes for targeted null mutations exhibit reduced pairing in meiotic prophase I and produce no mature germ cells. Mutants also display increased microsatellite instability and a predisposition for developing intestinal and other tumors. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700017B05Rik A G 9: 57,258,894 (GRCm38) W66R probably damaging Het
Adamts3 A G 5: 89,861,552 (GRCm38) V84A possibly damaging Het
Caap1 C A 4: 94,501,228 (GRCm38) E290* probably null Het
Cant1 G A 11: 118,408,050 (GRCm38) R296C probably damaging Het
Ccdc114 T A 7: 45,947,435 (GRCm38) D395E probably damaging Het
Cdh5 A T 8: 104,142,739 (GRCm38) H699L probably benign Het
Cfdp1 T C 8: 111,830,985 (GRCm38) T175A probably benign Het
Col4a4 C T 1: 82,493,591 (GRCm38) G681E unknown Het
Comtd1 G A 14: 21,848,793 (GRCm38) T27I probably benign Het
Copg1 T A 6: 87,892,270 (GRCm38) V155D probably damaging Het
Dag1 A G 9: 108,207,699 (GRCm38) Y748H possibly damaging Het
Dmwd T A 7: 19,080,281 (GRCm38) N285K possibly damaging Het
Dsp A G 13: 38,195,183 (GRCm38) E1968G possibly damaging Het
Ednra A G 8: 77,667,375 (GRCm38) I364T probably damaging Het
Elovl3 C A 19: 46,134,681 (GRCm38) T232K probably damaging Het
Ercc3 T A 18: 32,254,243 (GRCm38) I503N probably damaging Het
Ercc6 C A 14: 32,569,623 (GRCm38) A1008D probably benign Het
Gm10563 TTTC TTTCATTC 4: 155,614,496 (GRCm38) probably null Het
H2-DMb2 G T 17: 34,148,562 (GRCm38) V117F probably damaging Het
Helt A T 8: 46,292,433 (GRCm38) W138R probably damaging Het
Itga11 A T 9: 62,737,412 (GRCm38) H215L probably benign Het
Kcnn1 T A 8: 70,854,653 (GRCm38) I156F probably benign Het
Kdm1b A G 13: 47,062,969 (GRCm38) N272D probably benign Het
Kdm2b T C 5: 122,878,588 (GRCm38) T1161A probably damaging Het
Lin54 A G 5: 100,485,519 (GRCm38) L102P probably damaging Het
Naip2 G A 13: 100,152,560 (GRCm38) L1165F probably damaging Het
Nfkbiz A G 16: 55,819,641 (GRCm38) S118P probably damaging Het
Nkx3-2 T A 5: 41,761,848 (GRCm38) M266L probably benign Het
Npr1 T C 3: 90,457,002 (GRCm38) E771G probably benign Het
Obox8 C T 7: 14,332,029 (GRCm38) R188H probably benign Het
Olfr187 A T 16: 59,036,143 (GRCm38) V198D possibly damaging Het
Olfr497 T A 7: 108,423,402 (GRCm38) V277E possibly damaging Het
Palm3 T C 8: 84,021,530 (GRCm38) probably null Het
Palmd A T 3: 116,923,849 (GRCm38) V333D possibly damaging Het
Pikfyve A G 1: 65,267,829 (GRCm38) E1747G possibly damaging Het
Polr3a T C 14: 24,454,941 (GRCm38) I1084V possibly damaging Het
Ranbp3l T A 15: 9,007,203 (GRCm38) F127I probably benign Het
Rsl1d1 A G 16: 11,201,384 (GRCm38) F97L possibly damaging Het
Scaper A G 9: 55,864,546 (GRCm38) V362A probably benign Het
Scg5 A T 2: 113,776,865 (GRCm38) L192* probably null Het
Slc34a2 T C 5: 53,061,434 (GRCm38) I198T probably damaging Het
Slc45a3 T A 1: 131,978,194 (GRCm38) D318E possibly damaging Het
Sorl1 A G 9: 42,106,516 (GRCm38) M105T possibly damaging Het
St3gal5 T A 6: 72,149,131 (GRCm38) I320N probably damaging Het
Stx17 A G 4: 48,183,470 (GRCm38) probably benign Het
Syt5 C T 7: 4,541,075 (GRCm38) probably null Het
Thrap3 A G 4: 126,167,640 (GRCm38) S774P probably damaging Het
Tnc A T 4: 63,993,206 (GRCm38) M1376K probably benign Het
Tnks1bp1 T A 2: 85,062,754 (GRCm38) D1008E probably benign Het
Trav7-1 G T 14: 52,655,304 (GRCm38) A105S probably damaging Het
Vmn1r28 T A 6: 58,265,964 (GRCm38) V264D probably damaging Het
Vmn1r44 T C 6: 89,893,839 (GRCm38) V46A probably benign Het
Vmn2r10 A G 5: 108,995,720 (GRCm38) I788T probably damaging Het
Vmn2r78 T A 7: 86,920,124 (GRCm38) I75N probably damaging Het
Zfp821 T C 8: 109,724,359 (GRCm38) M328T probably damaging Het
Zfp995 G A 17: 21,880,623 (GRCm38) P210L possibly damaging Het
Other mutations in Mlh1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01306:Mlh1 APN 9 111,252,912 (GRCm38) missense possibly damaging 0.84
IGL02530:Mlh1 APN 9 111,229,875 (GRCm38) missense probably benign 0.09
IGL02811:Mlh1 APN 9 111,271,514 (GRCm38) missense probably benign 0.04
IGL02892:Mlh1 APN 9 111,252,969 (GRCm38) missense probably benign 0.00
IGL03394:Mlh1 APN 9 111,268,243 (GRCm38) missense probably damaging 1.00
andalusia UTSW 9 111,271,410 (GRCm38) makesense probably null
andalusia2 UTSW 9 111,271,523 (GRCm38) start codon destroyed probably null 0.93
andalusia3 UTSW 9 111,229,838 (GRCm38) critical splice donor site probably null
ANU23:Mlh1 UTSW 9 111,252,912 (GRCm38) missense possibly damaging 0.84
PIT4495001:Mlh1 UTSW 9 111,247,260 (GRCm38) missense probably benign 0.00
R0496:Mlh1 UTSW 9 111,241,556 (GRCm38) missense probably benign
R0723:Mlh1 UTSW 9 111,271,472 (GRCm38) missense probably damaging 1.00
R1395:Mlh1 UTSW 9 111,247,377 (GRCm38) missense probably damaging 1.00
R1694:Mlh1 UTSW 9 111,228,475 (GRCm38) missense probably damaging 1.00
R1762:Mlh1 UTSW 9 111,229,929 (GRCm38) missense probably damaging 1.00
R1865:Mlh1 UTSW 9 111,257,024 (GRCm38) intron probably benign
R1885:Mlh1 UTSW 9 111,258,556 (GRCm38) missense probably benign 0.18
R1992:Mlh1 UTSW 9 111,228,563 (GRCm38) missense probably damaging 0.96
R2186:Mlh1 UTSW 9 111,258,566 (GRCm38) unclassified probably benign
R2680:Mlh1 UTSW 9 111,236,017 (GRCm38) critical splice acceptor site probably null
R4693:Mlh1 UTSW 9 111,255,658 (GRCm38) missense probably damaging 1.00
R4784:Mlh1 UTSW 9 111,239,798 (GRCm38) missense probably benign
R5007:Mlh1 UTSW 9 111,271,410 (GRCm38) makesense probably null
R5130:Mlh1 UTSW 9 111,229,838 (GRCm38) critical splice donor site probably null
R5166:Mlh1 UTSW 9 111,241,513 (GRCm38) missense probably benign 0.04
R5481:Mlh1 UTSW 9 111,229,837 (GRCm38) splice site probably null
R5483:Mlh1 UTSW 9 111,231,058 (GRCm38) missense possibly damaging 0.82
R5602:Mlh1 UTSW 9 111,252,878 (GRCm38) missense probably damaging 0.97
R5658:Mlh1 UTSW 9 111,247,380 (GRCm38) missense probably damaging 0.99
R5890:Mlh1 UTSW 9 111,228,495 (GRCm38) missense possibly damaging 0.88
R6810:Mlh1 UTSW 9 111,241,558 (GRCm38) missense possibly damaging 0.52
R7607:Mlh1 UTSW 9 111,229,890 (GRCm38) missense probably damaging 1.00
R7753:Mlh1 UTSW 9 111,252,863 (GRCm38) critical splice donor site probably null
R7894:Mlh1 UTSW 9 111,230,077 (GRCm38) splice site probably null
R7912:Mlh1 UTSW 9 111,261,513 (GRCm38) missense possibly damaging 0.69
R7995:Mlh1 UTSW 9 111,235,921 (GRCm38) missense probably damaging 1.00
R8097:Mlh1 UTSW 9 111,256,092 (GRCm38) critical splice donor site probably null
R8280:Mlh1 UTSW 9 111,249,218 (GRCm38) critical splice donor site probably null
R8804:Mlh1 UTSW 9 111,264,904 (GRCm38) missense probably damaging 1.00
R9562:Mlh1 UTSW 9 111,230,945 (GRCm38) missense
Predicted Primers PCR Primer

Sequencing Primer
Posted On 2016-07-06