Incidental Mutation 'R1885:Mlh1'
ID 209456
Institutional Source Beutler Lab
Gene Symbol Mlh1
Ensembl Gene ENSMUSG00000032498
Gene Name mutL homolog 1
Synonyms 1110035C23Rik, colon cancer, nonpolyposis type 2
MMRRC Submission 039906-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1885 (G1)
Quality Score 225
Status Not validated
Chromosome 9
Chromosomal Location 111057296-111100854 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 111087624 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Isoleucine at position 24 (S24I)
Ref Sequence ENSEMBL: ENSMUSP00000119170 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000035079] [ENSMUST00000135218] [ENSMUST00000135695]
AlphaFold Q9JK91
Predicted Effect probably benign
Transcript: ENSMUST00000035079
AA Change: S129I

PolyPhen 2 Score 0.043 (Sensitivity: 0.94; Specificity: 0.83)
SMART Domains Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: S129I

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 noncoding transcript
Transcript: ENSMUST00000123869
Predicted Effect noncoding transcript
Transcript: ENSMUST00000134316
Predicted Effect probably benign
Transcript: ENSMUST00000135218
Predicted Effect probably benign
Transcript: ENSMUST00000135695
AA Change: S24I

PolyPhen 2 Score 0.178 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000119170
Gene: ENSMUSG00000032498
AA Change: S24I

DomainStartEndE-ValueType
Blast:HATPase_c 1 53 8e-33 BLAST
SCOP:d1b63a2 1 75 7e-22 SMART
PDB:4P7A|A 1 76 2e-47 PDB
Predicted Effect probably benign
Transcript: ENSMUST00000199404
Coding Region Coverage
  • 1x: 97.0%
  • 3x: 96.1%
  • 10x: 92.7%
  • 20x: 85.1%
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: 84 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700102P08Rik T A 9: 108,270,809 (GRCm39) D124E possibly damaging Het
Aarsd1 T C 11: 101,302,227 (GRCm39) T278A probably benign Het
Acox2 C T 14: 8,248,102 (GRCm38) M393I probably benign Het
Adcy10 A G 1: 165,398,377 (GRCm39) I1491M probably benign Het
Adcy3 T A 12: 4,184,951 (GRCm39) V209E probably damaging Het
Adora3 A C 3: 105,812,152 (GRCm39) N13H possibly damaging Het
Ap2b1 T A 11: 83,281,561 (GRCm39) N822K probably damaging Het
Apobec3 A T 15: 79,781,906 (GRCm39) H82L probably damaging Het
Atg9b A T 5: 24,593,252 (GRCm39) W384R probably damaging Het
Atp8a1 A G 5: 67,904,661 (GRCm39) V506A possibly damaging Het
Atxn1 G T 13: 45,721,280 (GRCm39) A205D probably benign Het
B4galnt3 T C 6: 120,200,601 (GRCm39) E223G probably damaging Het
Brip1 C A 11: 86,029,641 (GRCm39) G631V probably damaging Het
Cacna1i A G 15: 80,243,145 (GRCm39) E434G probably damaging Het
Caprin2 A T 6: 148,779,383 (GRCm39) probably null Het
Cblif G A 19: 11,729,688 (GRCm39) A216T probably benign Het
Ccdc80 A C 16: 44,917,083 (GRCm39) D613A probably benign Het
Ccdc81 T C 7: 89,515,819 (GRCm39) E620G possibly damaging Het
Cdhr18 A C 14: 13,828,607 (GRCm38) Y718D probably damaging Het
Cebpz A T 17: 79,239,545 (GRCm39) D625E probably benign Het
Coq6 C A 12: 84,419,238 (GRCm39) N388K probably damaging Het
Cracd A G 5: 77,004,589 (GRCm39) T317A unknown Het
D430041D05Rik T C 2: 104,060,800 (GRCm39) M1365V probably benign Het
Dab1 C T 4: 104,588,948 (GRCm39) A524V probably benign Het
Dap3 A G 3: 88,838,281 (GRCm39) L86P probably damaging Het
Dpysl4 T G 7: 138,676,723 (GRCm39) V391G probably damaging Het
Dyrk4 G T 6: 126,854,144 (GRCm39) Q550K probably benign Het
Epas1 A G 17: 87,112,723 (GRCm39) D107G probably damaging Het
Esrp2 A G 8: 106,858,453 (GRCm39) V636A possibly damaging Het
Etl4 T A 2: 20,748,795 (GRCm39) Y176N probably damaging Het
Etnppl T C 3: 130,423,111 (GRCm39) V264A probably benign Het
Ezhip GTCATCATCATCATC GTCATCATCATCATCATC X: 5,994,645 (GRCm39) probably benign Het
Fer T A 17: 64,445,909 (GRCm39) V790D probably damaging Het
Gdpd5 G A 7: 99,109,204 (GRCm39) V575I probably benign Het
Gfus G T 15: 75,798,838 (GRCm39) T123N possibly damaging Het
Gipc3 T C 10: 81,177,181 (GRCm39) I130V probably benign Het
Iqsec3 G A 6: 121,405,326 (GRCm39) probably benign Het
Kdm5d G T Y: 940,781 (GRCm39) probably null Het
Kl A G 5: 150,876,959 (GRCm39) R260G possibly damaging Het
Kras T C 6: 145,177,843 (GRCm39) E143G probably damaging Het
Ksr1 T C 11: 78,927,347 (GRCm39) T329A probably damaging Het
Ksr1 C A 11: 78,911,204 (GRCm39) V11F probably null Het
Marchf6 A G 15: 31,502,952 (GRCm39) V83A probably benign Het
Mettl2 T C 11: 105,022,446 (GRCm39) I212T possibly damaging Het
Mgat3 A G 15: 80,095,820 (GRCm39) I216V probably benign Het
Mkrn3 G A 7: 62,068,486 (GRCm39) A435V probably benign Het
Mmel1 G A 4: 154,975,333 (GRCm39) R424Q possibly damaging Het
Mob3a G A 10: 80,527,068 (GRCm39) Q86* probably null Het
Myh3 A G 11: 66,977,453 (GRCm39) K368E probably benign Het
Myo16 T A 8: 10,372,656 (GRCm39) N118K probably damaging Het
Myo5c A G 9: 75,157,043 (GRCm39) S160G probably damaging Het
Nat1 A T 8: 67,943,653 (GRCm39) I13F probably damaging Het
Ncoa7 T C 10: 30,524,448 (GRCm39) N823S possibly damaging Het
Nwd1 T C 8: 73,431,622 (GRCm39) S1207P probably benign Het
Or2y17 T C 11: 49,231,662 (GRCm39) L101P probably damaging Het
Or4k49 G T 2: 111,495,099 (GRCm39) S176I probably damaging Het
Or5p57 T C 7: 107,665,985 (GRCm39) N7D probably benign Het
Or5w22 T C 2: 87,363,168 (GRCm39) S264P probably damaging Het
Paqr8 A T 1: 21,005,704 (GRCm39) H286L probably damaging Het
Pdzd4 G A X: 72,839,052 (GRCm39) R419C probably damaging Het
Pes1 A G 11: 3,919,482 (GRCm39) K52E probably damaging Het
Ppp1r13l T C 7: 19,111,496 (GRCm39) S774P probably damaging Het
Robo2 T C 16: 73,713,033 (GRCm39) D1283G probably benign Het
Rp1l1 T C 14: 64,265,839 (GRCm39) V475A probably benign Het
Scml4 A G 10: 42,788,223 (GRCm39) Y51C probably damaging Het
Skic3 A T 13: 76,261,166 (GRCm39) R112S probably benign Het
Skic3 A G 13: 76,278,354 (GRCm39) Q556R probably benign Het
Slc2a4 C T 11: 69,835,833 (GRCm39) V339I probably benign Het
Slc39a6 G A 18: 24,734,539 (GRCm39) probably null Het
Slco1b2 A T 6: 141,628,951 (GRCm39) Y551F probably damaging Het
Snx33 T C 9: 56,833,121 (GRCm39) H316R probably benign Het
Spata31d1a T G 13: 59,849,821 (GRCm39) D769A probably damaging Het
Stmn2 A T 3: 8,606,964 (GRCm39) E28V probably damaging Het
Syt9 A G 7: 107,035,736 (GRCm39) D251G probably damaging Het
Tjap1 T C 17: 46,573,347 (GRCm39) T37A probably damaging Het
Tmc7 A T 7: 118,160,310 (GRCm39) F176I possibly damaging Het
Tprg1 A G 16: 25,231,641 (GRCm39) T206A probably benign Het
Ubqlnl A T 7: 103,799,272 (GRCm39) M75K possibly damaging Het
Vmn2r115 ATCTTCT ATCT 17: 23,578,962 (GRCm39) probably benign Het
Vmn2r12 C T 5: 109,239,942 (GRCm39) G207E probably damaging Het
Xrn2 T G 2: 146,891,281 (GRCm39) L697* probably null Het
Zfp764 A G 7: 127,004,211 (GRCm39) F307L probably benign Het
Zfp804b T C 5: 6,820,376 (GRCm39) R860G probably damaging Het
Zranb2 A T 3: 157,248,793 (GRCm39) probably null 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
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
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'- CCCCTATAGACAAGAAGGTGGG -3'
(R):5'- CCCACAGATTAATTTCTCAATGCC -3'

Sequencing Primer
(F):5'- CCAATGATCATTTATCTTGGGACTTC -3'
(R):5'- TGGAACTCACTCTGTAGACCAGG -3'
Posted On 2014-06-30