Incidental Mutation 'R1992:Mlh1'
ID 223676
Institutional Source Beutler Lab
Gene Symbol Mlh1
Ensembl Gene ENSMUSG00000032498
Gene Name mutL homolog 1
Synonyms 1110035C23Rik, colon cancer, nonpolyposis type 2
MMRRC Submission 040003-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1992 (G1)
Quality Score 201
Status Not validated
Chromosome 9
Chromosomal Location 111057296-111100854 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 111057631 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Alanine to Threonine at position 727 (A727T)
Ref Sequence ENSEMBL: ENSMUSP00000035079 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000035078] [ENSMUST00000035079] [ENSMUST00000098340] [ENSMUST00000135218] [ENSMUST00000216430] [ENSMUST00000217117] [ENSMUST00000197241] [ENSMUST00000197256] [ENSMUST00000196981]
AlphaFold Q9JK91
Predicted Effect probably benign
Transcript: ENSMUST00000035078
SMART Domains Protein: ENSMUSP00000035078
Gene: ENSMUSG00000032497

DomainStartEndE-ValueType
Pfam:DUF2051 31 340 2.5e-106 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000035079
AA Change: A727T

PolyPhen 2 Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: A727T

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: ENSMUST00000098340
SMART Domains Protein: ENSMUSP00000095944
Gene: ENSMUSG00000032497

DomainStartEndE-ValueType
Pfam:DUF2051 31 326 2.7e-122 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000123869
Predicted Effect noncoding transcript
Transcript: ENSMUST00000128795
Predicted Effect probably benign
Transcript: ENSMUST00000135218
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196906
Predicted Effect noncoding transcript
Transcript: ENSMUST00000197540
Predicted Effect noncoding transcript
Transcript: ENSMUST00000200145
Predicted Effect probably benign
Transcript: ENSMUST00000216430
Predicted Effect probably benign
Transcript: ENSMUST00000217117
Predicted Effect probably benign
Transcript: ENSMUST00000197241
SMART Domains Protein: ENSMUSP00000142816
Gene: ENSMUSG00000032497

DomainStartEndE-ValueType
Pfam:DUF2051 31 341 1.3e-119 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000197256
SMART Domains Protein: ENSMUSP00000143322
Gene: ENSMUSG00000032497

DomainStartEndE-ValueType
Pfam:DUF2051 31 363 2.9e-115 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000196981
SMART Domains Protein: ENSMUSP00000142851
Gene: ENSMUSG00000032497

DomainStartEndE-ValueType
Pfam:DUF2051 31 350 4.5e-113 PFAM
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.4%
  • 20x: 92.5%
Validation Efficiency
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: 123 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310009B15Rik T C 1: 138,781,380 (GRCm39) T90A probably damaging Het
A930011G23Rik T C 5: 99,381,784 (GRCm39) D326G possibly damaging Het
Abcc2 A T 19: 43,795,581 (GRCm39) I446F probably damaging Het
Adam34l T C 8: 44,080,176 (GRCm39) K16R probably benign Het
Adamts14 A G 10: 61,034,439 (GRCm39) Y1150H probably benign Het
Adgrl2 A G 3: 148,522,880 (GRCm39) I217T possibly damaging Het
Afap1l1 A T 18: 61,874,842 (GRCm39) Y446* probably null Het
Aimp2 G A 5: 143,843,548 (GRCm39) A14V probably damaging Het
Akap8 G A 17: 32,535,586 (GRCm39) H143Y probably damaging Het
Aldh2 A T 5: 121,714,026 (GRCm39) V207E possibly damaging Het
Aoc1l2 T A 6: 48,907,703 (GRCm39) H234Q probably damaging Het
Armc3 T C 2: 19,297,953 (GRCm39) Y575H probably damaging Het
Arpp21 T C 9: 111,986,861 (GRCm39) E230G probably damaging Het
Arrdc3 G A 13: 81,031,808 (GRCm39) D14N probably damaging Het
Atn1 A G 6: 124,722,291 (GRCm39) probably benign Het
Atxn7l1 G A 12: 33,408,743 (GRCm39) D302N probably damaging Het
Bbs1 T A 19: 4,941,736 (GRCm39) H518L probably benign Het
Bltp1 A T 3: 37,054,181 (GRCm39) H3100L probably benign Het
Bmpr1a C A 14: 34,147,050 (GRCm39) G241C probably damaging Het
Cacna1b G A 2: 24,622,318 (GRCm39) P222L probably damaging Het
Calcrl T C 2: 84,200,855 (GRCm39) Y63C probably damaging Het
Cand2 A G 6: 115,762,093 (GRCm39) H173R possibly damaging Het
Cap2 T A 13: 46,791,357 (GRCm39) Y175N possibly damaging Het
Card14 A T 11: 119,212,647 (GRCm39) probably null Het
Cd3d T A 9: 44,896,299 (GRCm39) Y29* probably null Het
Cd4 A G 6: 124,844,651 (GRCm39) V378A possibly damaging Het
Cluh A T 11: 74,550,828 (GRCm39) H318L probably damaging Het
Clvs1 T A 4: 9,281,899 (GRCm39) D114E probably benign Het
Cnot4 T A 6: 35,000,344 (GRCm39) T548S probably benign Het
Col18a1 T C 10: 76,916,988 (GRCm39) I114V unknown Het
Cr2 G A 1: 194,836,458 (GRCm39) P1278S possibly damaging Het
Crebbp A T 16: 3,946,561 (GRCm39) probably null Het
Dnah7a T G 1: 53,621,835 (GRCm39) K1097Q possibly damaging Het
Doc2a T A 7: 126,450,979 (GRCm39) probably null Het
Dpp10 A T 1: 123,832,833 (GRCm39) V48E probably null Het
Dsg2 A G 18: 20,734,530 (GRCm39) K836R probably damaging Het
Egr2 T C 10: 67,375,857 (GRCm39) V164A probably damaging Het
Erbin A T 13: 103,970,221 (GRCm39) S1132T probably benign Het
Espn T A 4: 152,213,012 (GRCm39) probably null Het
Fam83b A G 9: 76,399,304 (GRCm39) S600P probably benign Het
Fanca A T 8: 124,024,551 (GRCm39) N425K possibly damaging Het
Flot2 C T 11: 77,949,445 (GRCm39) L294F probably damaging Het
Frs2 A G 10: 116,910,459 (GRCm39) V301A probably benign Het
Fv1 T A 4: 147,953,618 (GRCm39) N61K possibly damaging Het
Fxr2 A G 11: 69,540,659 (GRCm39) E339G possibly damaging Het
Gck T C 11: 5,856,515 (GRCm39) Y214C probably damaging Het
Golga3 C G 5: 110,340,839 (GRCm39) T551R probably damaging Het
Gorab A G 1: 163,224,625 (GRCm39) S59P probably damaging Het
Gsdme C T 6: 50,185,102 (GRCm39) V451M probably damaging Het
H2-T13 A C 17: 36,391,938 (GRCm39) I216S probably damaging Het
Herc4 T A 10: 63,081,743 (GRCm39) V22E possibly damaging Het
Hjurp GT GTT 1: 88,194,246 (GRCm39) probably null Het
Hoxa2 A T 6: 52,141,576 (GRCm39) S17T probably damaging Het
Hs3st5 A G 10: 36,708,882 (GRCm39) Y139C probably damaging Het
Ism1 G A 2: 139,587,937 (GRCm39) V221I probably benign Het
Kalrn T G 16: 33,796,108 (GRCm39) L1222F probably damaging Het
Katnip A G 7: 125,419,261 (GRCm39) N476S probably benign Het
Kdm4c A G 4: 74,261,631 (GRCm39) D602G possibly damaging Het
Ktn1 A G 14: 47,932,978 (GRCm39) K711E probably damaging Het
Lce1k A T 3: 92,714,125 (GRCm39) C20S unknown Het
Macf1 A G 4: 123,350,488 (GRCm39) S3792P probably damaging Het
Maml3 C T 3: 51,598,178 (GRCm39) M189I probably benign Het
Mcc C A 18: 44,624,382 (GRCm39) E213* probably null Het
Mep1a T G 17: 43,813,573 (GRCm39) I13L probably benign Het
Mkrn2 G T 6: 115,586,562 (GRCm39) C16F probably damaging Het
Muc21 A T 17: 35,929,600 (GRCm39) S1529T probably benign Het
Naa16 T C 14: 79,593,931 (GRCm39) Y344C probably damaging Het
Nebl T A 2: 17,457,321 (GRCm39) I80F probably damaging Het
Nlrc4 T A 17: 74,752,628 (GRCm39) Y585F probably benign Het
Nrcam A G 12: 44,587,753 (GRCm39) K149R probably damaging Het
Nufip1 T A 14: 76,372,287 (GRCm39) I467N probably damaging Het
Nup133 A G 8: 124,632,960 (GRCm39) I1057T possibly damaging Het
Obscn A T 11: 58,886,653 (GRCm39) probably benign Het
Or10ag52 T A 2: 87,043,588 (GRCm39) C117* probably null Het
Or5k1 A G 16: 58,617,309 (GRCm39) V300A probably benign Het
Or5k14 A C 16: 58,692,874 (GRCm39) I213R probably benign Het
Pi4k2a A T 19: 42,104,377 (GRCm39) I380F probably damaging Het
Piezo2 A T 18: 63,207,733 (GRCm39) L1426Q probably null Het
Pik3cg A T 12: 32,254,024 (GRCm39) D654E possibly damaging Het
Poli G T 18: 70,642,058 (GRCm39) P714Q probably damaging Het
Polr3f A G 2: 144,378,230 (GRCm39) N201D probably benign Het
Prorp A G 12: 55,384,991 (GRCm39) D89G probably damaging Het
Ptprz1 A T 6: 22,959,747 (GRCm39) K81N probably benign Het
Rbm19 T C 5: 120,271,948 (GRCm39) probably null Het
Sec24a C T 11: 51,627,190 (GRCm39) V241I probably benign Het
Sgk3 A G 1: 9,950,567 (GRCm39) T160A possibly damaging Het
Slc1a4 A G 11: 20,254,375 (GRCm39) I497T probably benign Het
Slc26a9 A T 1: 131,690,532 (GRCm39) D512V probably damaging Het
Slc43a3 C T 2: 84,788,084 (GRCm39) R489C probably damaging Het
Slc5a12 T A 2: 110,452,089 (GRCm39) F327L probably benign Het
Slitrk3 A G 3: 72,957,104 (GRCm39) V556A possibly damaging Het
Spata6l A G 19: 28,926,024 (GRCm39) F130L probably damaging Het
Spib T C 7: 44,178,281 (GRCm39) E180G probably benign Het
Spint2 T A 7: 28,958,833 (GRCm39) N128Y probably damaging Het
Spx G A 6: 142,364,245 (GRCm39) G102E probably benign Het
Spz1 T A 13: 92,712,166 (GRCm39) E103D possibly damaging Het
Sstr2 T C 11: 113,515,495 (GRCm39) I138T probably benign Het
Sytl3 T A 17: 7,000,448 (GRCm39) I206N possibly damaging Het
Tcaf2 T C 6: 42,606,791 (GRCm39) T388A probably benign Het
Tdpoz8 G T 3: 92,981,344 (GRCm39) A121S probably benign Het
Thap12 T C 7: 98,365,572 (GRCm39) V580A possibly damaging Het
Tlr5 T A 1: 182,801,912 (GRCm39) D405E probably damaging Het
Tnxb T C 17: 34,890,878 (GRCm39) V407A probably damaging Het
Tpx2 T A 2: 152,732,544 (GRCm39) M606K probably benign Het
Trim43a T G 9: 88,466,312 (GRCm39) L211R probably damaging Het
Trim46 A T 3: 89,145,008 (GRCm39) Y489N probably damaging Het
Ttc28 C T 5: 111,424,188 (GRCm39) S1485L probably benign Het
Ttll8 T C 15: 88,798,654 (GRCm39) T694A probably benign Het
Txnl1 T C 18: 63,812,585 (GRCm39) T70A probably benign Het
Ube3a C T 7: 58,953,535 (GRCm39) A823V probably damaging Het
Ubqln5 C A 7: 103,778,741 (GRCm39) V28F probably damaging Het
Ulk1 T A 5: 110,935,017 (GRCm39) Q972L probably damaging Het
Unc93b1 T C 19: 3,994,062 (GRCm39) Y398H probably benign Het
Usp1 A G 4: 98,822,531 (GRCm39) D615G probably benign Het
Utp15 A G 13: 98,387,420 (GRCm39) C385R probably benign Het
Vmn2r91 T A 17: 18,356,142 (GRCm39) V603D probably damaging Het
Whamm C T 7: 81,241,519 (GRCm39) R277* probably null Het
Wnt8a A G 18: 34,677,937 (GRCm39) D115G probably damaging Het
Yjefn3 A T 8: 70,341,645 (GRCm39) probably null Het
Ywhab A T 2: 163,853,807 (GRCm39) I95F probably damaging Het
Zfp143 C T 7: 109,660,489 (GRCm39) probably benign Het
Zfp607b C G 7: 27,401,949 (GRCm39) T135R possibly damaging Het
Zfp970 A G 2: 177,166,663 (GRCm39) Q79R 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
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
R5265:Mlh1 UTSW 9 111,100,591 (GRCm39) start codon destroyed probably null 0.93
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'- AATAGTGAGCACTGGAAACCC -3'
(R):5'- CTTTGTAAGCCTTGCACAGCTC -3'

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