Incidental Mutation 'R5265:Mlh1'
ID 401667
Institutional Source Beutler Lab
Gene Symbol Mlh1
Ensembl Gene ENSMUSG00000032498
Gene Name mutL homolog 1
Synonyms 1110035C23Rik, colon cancer, nonpolyposis type 2
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 111057296-111100854 bp(-) (GRCm39)
Type of Mutation start codon destroyed
DNA Base Change (assembly) A to C at 111100591 bp (GRCm39)
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

DomainStartEndE-ValueType
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: 57,166,177 (GRCm39) W66R probably damaging Het
Adamts3 A G 5: 90,009,411 (GRCm39) V84A possibly damaging Het
Caap1 C A 4: 94,389,465 (GRCm39) E290* probably null Het
Cant1 G A 11: 118,298,876 (GRCm39) R296C probably damaging Het
Cdh5 A T 8: 104,869,371 (GRCm39) H699L probably benign Het
Cfdp1 T C 8: 112,557,617 (GRCm39) T175A probably benign Het
Col4a4 C T 1: 82,471,312 (GRCm39) G681E unknown Het
Comtd1 G A 14: 21,898,861 (GRCm39) T27I probably benign Het
Copg1 T A 6: 87,869,252 (GRCm39) V155D probably damaging Het
Dag1 A G 9: 108,084,898 (GRCm39) Y748H possibly damaging Het
Dmwd T A 7: 18,814,206 (GRCm39) N285K possibly damaging Het
Dsp A G 13: 38,379,159 (GRCm39) E1968G possibly damaging Het
Ednra A G 8: 78,394,004 (GRCm39) I364T probably damaging Het
Elovl3 C A 19: 46,123,120 (GRCm39) T232K probably damaging Het
Ercc3 T A 18: 32,387,296 (GRCm39) I503N probably damaging Het
Ercc6 C A 14: 32,291,580 (GRCm39) A1008D probably benign Het
Gm10563 TTTC TTTCATTC 4: 155,698,953 (GRCm39) probably null Het
H2-DMb2 G T 17: 34,367,536 (GRCm39) V117F probably damaging Het
Helt A T 8: 46,745,470 (GRCm39) W138R probably damaging Het
Itga11 A T 9: 62,644,694 (GRCm39) H215L probably benign Het
Kcnn1 T A 8: 71,307,297 (GRCm39) I156F probably benign Het
Kdm1b A G 13: 47,216,445 (GRCm39) N272D probably benign Het
Kdm2b T C 5: 123,016,651 (GRCm39) T1161A probably damaging Het
Lin54 A G 5: 100,633,378 (GRCm39) L102P probably damaging Het
Naip2 G A 13: 100,289,068 (GRCm39) L1165F probably damaging Het
Nfkbiz A G 16: 55,640,004 (GRCm39) S118P probably damaging Het
Nkx3-2 T A 5: 41,919,191 (GRCm39) M266L probably benign Het
Npr1 T C 3: 90,364,309 (GRCm39) E771G probably benign Het
Obox8 C T 7: 14,065,954 (GRCm39) R188H probably benign Het
Odad1 T A 7: 45,596,859 (GRCm39) D395E probably damaging Het
Or5h19 A T 16: 58,856,506 (GRCm39) V198D possibly damaging Het
Or5p72 T A 7: 108,022,609 (GRCm39) V277E possibly damaging Het
Palm3 T C 8: 84,748,159 (GRCm39) probably null Het
Palmd A T 3: 116,717,498 (GRCm39) V333D possibly damaging Het
Pikfyve A G 1: 65,306,988 (GRCm39) E1747G possibly damaging Het
Polr3a T C 14: 24,505,009 (GRCm39) I1084V possibly damaging Het
Ranbp3l T A 15: 9,037,077 (GRCm39) F127I probably benign Het
Rsl1d1 A G 16: 11,019,248 (GRCm39) F97L possibly damaging Het
Scaper A G 9: 55,771,830 (GRCm39) V362A probably benign Het
Scg5 A T 2: 113,607,210 (GRCm39) L192* probably null Het
Slc34a2 T C 5: 53,218,776 (GRCm39) I198T probably damaging Het
Slc45a3 T A 1: 131,905,932 (GRCm39) D318E possibly damaging Het
Sorl1 A G 9: 42,017,812 (GRCm39) M105T possibly damaging Het
St3gal5 T A 6: 72,126,115 (GRCm39) I320N probably damaging Het
Stx17 A G 4: 48,183,470 (GRCm39) probably benign Het
Syt5 C T 7: 4,544,074 (GRCm39) probably null Het
Thrap3 A G 4: 126,061,433 (GRCm39) S774P probably damaging Het
Tnc A T 4: 63,911,443 (GRCm39) M1376K probably benign Het
Tnks1bp1 T A 2: 84,893,098 (GRCm39) D1008E probably benign Het
Trav7-1 G T 14: 52,892,761 (GRCm39) A105S probably damaging Het
Vmn1r28 T A 6: 58,242,949 (GRCm39) V264D probably damaging Het
Vmn1r44 T C 6: 89,870,821 (GRCm39) V46A probably benign Het
Vmn2r10 A G 5: 109,143,586 (GRCm39) I788T probably damaging Het
Vmn2r78 T A 7: 86,569,332 (GRCm39) I75N probably damaging Het
Zfp821 T C 8: 110,450,991 (GRCm39) M328T probably damaging Het
Zfp995 G A 17: 22,099,604 (GRCm39) P210L possibly damaging Het
Other mutations in Mlh1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01306:Mlh1 APN 9 111,081,980 (GRCm39) missense possibly damaging 0.84
IGL02530:Mlh1 APN 9 111,058,943 (GRCm39) missense probably benign 0.09
IGL02811:Mlh1 APN 9 111,100,582 (GRCm39) missense probably benign 0.04
IGL02892:Mlh1 APN 9 111,082,037 (GRCm39) missense probably benign 0.00
IGL03394:Mlh1 APN 9 111,097,311 (GRCm39) missense probably damaging 1.00
andalusia UTSW 9 111,100,478 (GRCm39) makesense probably null
andalusia2 UTSW 9 111,100,591 (GRCm39) start codon destroyed probably null 0.93
andalusia3 UTSW 9 111,058,906 (GRCm39) critical splice donor site probably null
ANU23:Mlh1 UTSW 9 111,081,980 (GRCm39) missense possibly damaging 0.84
PIT4495001:Mlh1 UTSW 9 111,076,328 (GRCm39) missense probably benign 0.00
R0496:Mlh1 UTSW 9 111,070,624 (GRCm39) missense probably benign
R0723:Mlh1 UTSW 9 111,100,540 (GRCm39) missense probably damaging 1.00
R1395:Mlh1 UTSW 9 111,076,445 (GRCm39) missense probably damaging 1.00
R1694:Mlh1 UTSW 9 111,057,543 (GRCm39) missense probably damaging 1.00
R1762:Mlh1 UTSW 9 111,058,997 (GRCm39) missense probably damaging 1.00
R1865:Mlh1 UTSW 9 111,086,092 (GRCm39) intron probably benign
R1885:Mlh1 UTSW 9 111,087,624 (GRCm39) missense probably benign 0.18
R1992:Mlh1 UTSW 9 111,057,631 (GRCm39) missense probably damaging 0.96
R2186:Mlh1 UTSW 9 111,087,634 (GRCm39) unclassified probably benign
R2680:Mlh1 UTSW 9 111,065,085 (GRCm39) critical splice acceptor site probably null
R4693:Mlh1 UTSW 9 111,084,726 (GRCm39) missense probably damaging 1.00
R4784:Mlh1 UTSW 9 111,068,866 (GRCm39) missense probably benign
R5007:Mlh1 UTSW 9 111,100,478 (GRCm39) makesense probably null
R5130:Mlh1 UTSW 9 111,058,906 (GRCm39) critical splice donor site probably null
R5166:Mlh1 UTSW 9 111,070,581 (GRCm39) missense probably benign 0.04
R5481:Mlh1 UTSW 9 111,058,905 (GRCm39) splice site probably null
R5483:Mlh1 UTSW 9 111,060,126 (GRCm39) missense possibly damaging 0.82
R5602:Mlh1 UTSW 9 111,081,946 (GRCm39) missense probably damaging 0.97
R5658:Mlh1 UTSW 9 111,076,448 (GRCm39) missense probably damaging 0.99
R5890:Mlh1 UTSW 9 111,057,563 (GRCm39) missense possibly damaging 0.88
R6810:Mlh1 UTSW 9 111,070,626 (GRCm39) missense possibly damaging 0.52
R7607:Mlh1 UTSW 9 111,058,958 (GRCm39) missense probably damaging 1.00
R7753:Mlh1 UTSW 9 111,081,931 (GRCm39) critical splice donor site probably null
R7894:Mlh1 UTSW 9 111,059,145 (GRCm39) splice site probably null
R7912:Mlh1 UTSW 9 111,090,581 (GRCm39) missense possibly damaging 0.69
R7995:Mlh1 UTSW 9 111,064,989 (GRCm39) missense probably damaging 1.00
R8097:Mlh1 UTSW 9 111,085,160 (GRCm39) critical splice donor site probably null
R8280:Mlh1 UTSW 9 111,078,286 (GRCm39) critical splice donor site probably null
R8804:Mlh1 UTSW 9 111,093,972 (GRCm39) missense probably damaging 1.00
R9562:Mlh1 UTSW 9 111,060,013 (GRCm39) missense
Predicted Primers PCR Primer
(F):5'- CCGTGTGCATAATGGGAAAC -3'
(R):5'- TTTAGAGCGGGACAGAGATCC -3'

Sequencing Primer
(F):5'- GAAACCAGCCTGGCACG -3'
(R):5'- CGGGACAGAGATCCCAGGAAC -3'
Posted On 2016-07-06