Incidental Mutation 'R5602:Mlh1'
ID 439089
Institutional Source Beutler Lab
Gene Symbol Mlh1
Ensembl Gene ENSMUSG00000032498
Gene Name mutL homolog 1
Synonyms 1110035C23Rik, colon cancer, nonpolyposis type 2
MMRRC Submission 043154-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R5602 (G1)
Quality Score 225
Status Not validated
Chromosome 9
Chromosomal Location 111057296-111100854 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 111081946 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Glutamine at position 259 (L259Q)
Ref Sequence ENSEMBL: ENSMUSP00000035079 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000035079] [ENSMUST00000135218] [ENSMUST00000135695]
AlphaFold Q9JK91
Predicted Effect probably damaging
Transcript: ENSMUST00000035079
AA Change: L259Q

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: L259Q

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
SMART Domains Protein: ENSMUSP00000119170
Gene: ENSMUSG00000032498

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 unknown
Transcript: ENSMUST00000199404
AA Change: L53Q
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.6%
  • 20x: 96.2%
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: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921509C19Rik G A 2: 151,315,459 (GRCm39) S73F possibly damaging Het
4932414N04Rik A T 2: 68,578,712 (GRCm39) *753L probably null Het
Acyp2 C T 11: 30,456,354 (GRCm39) E98K possibly damaging Het
Adam19 T C 11: 46,027,142 (GRCm39) S592P probably benign Het
Adamtsl3 A G 7: 82,206,447 (GRCm39) K843R possibly damaging Het
Ap2a2 A T 7: 141,184,855 (GRCm39) T213S probably benign Het
Asb5 A G 8: 55,038,974 (GRCm39) E280G probably benign Het
Becn1 T C 11: 101,179,778 (GRCm39) D403G probably damaging Het
Ccr7 G T 11: 99,036,315 (GRCm39) N202K probably benign Het
Cd36 T C 5: 18,019,790 (GRCm39) T104A possibly damaging Het
Cnot4 C T 6: 35,028,464 (GRCm39) W384* probably null Het
Col15a1 G A 4: 47,312,087 (GRCm39) V1301M probably damaging Het
Dock2 C A 11: 34,204,391 (GRCm39) A1384S probably benign Het
Ehbp1l1 T C 19: 5,758,698 (GRCm39) E1648G possibly damaging Het
Fbn1 G T 2: 125,163,661 (GRCm39) A2065E possibly damaging Het
Fras1 A G 5: 96,884,880 (GRCm39) Y2586C probably damaging Het
Galm T A 17: 80,457,568 (GRCm39) Y28* probably null Het
Ggt7 A G 2: 155,332,919 (GRCm39) V648A possibly damaging Het
Gm17067 T A 7: 42,357,839 (GRCm39) D221V probably damaging Het
Gpr3 T C 4: 132,937,805 (GRCm39) N289S probably damaging Het
Ighv11-2 A G 12: 114,012,277 (GRCm39) probably benign Het
Ighv11-2 G A 12: 114,012,099 (GRCm39) L39F probably damaging Het
Ipo9 G A 1: 135,329,983 (GRCm39) L486F probably damaging Het
Jak2 T A 19: 29,275,739 (GRCm39) N726K probably benign Het
Map4 T C 9: 109,881,768 (GRCm39) S211P possibly damaging Het
Naa25 A G 5: 121,558,558 (GRCm39) E300G probably benign Het
Or8g34 A T 9: 39,373,326 (GRCm39) M200L probably benign Het
Or8g54 T A 9: 39,707,490 (GRCm39) V273E possibly damaging Het
Parva G A 7: 112,166,972 (GRCm39) V182I probably benign Het
Pcdhgb4 T C 18: 37,854,697 (GRCm39) I364T probably damaging Het
Pdik1l A G 4: 134,011,580 (GRCm39) S164P probably damaging Het
Pfas A T 11: 68,881,871 (GRCm39) I938N probably benign Het
Plscr1l1 G A 9: 92,234,721 (GRCm39) C152Y possibly damaging Het
Prdm4 TCTCCTCCT TCTCCT 10: 85,728,987 (GRCm39) probably null Het
Prob1 C T 18: 35,787,079 (GRCm39) V392M possibly damaging Het
Rasgrf1 T C 9: 89,793,624 (GRCm39) S134P possibly damaging Het
Rorb T A 19: 18,955,301 (GRCm39) Y20F probably damaging Het
Rsph9 G T 17: 46,445,909 (GRCm39) D220E probably damaging Het
Safb2 C A 17: 56,882,630 (GRCm39) K334N possibly damaging Het
Sall3 T C 18: 81,016,027 (GRCm39) T634A probably benign Het
Scaf1 A G 7: 44,657,007 (GRCm39) probably benign Het
Slco1a5 T A 6: 142,221,255 (GRCm39) probably benign Het
Spata21 C T 4: 140,824,210 (GRCm39) R158C probably benign Het
Srrm2 G A 17: 24,038,311 (GRCm39) probably benign Het
Stk38l C A 6: 146,659,998 (GRCm39) T10N probably benign Het
Supv3l1 G A 10: 62,266,371 (GRCm39) P602S possibly damaging Het
Timm44 C T 8: 4,316,769 (GRCm39) probably null Het
Tll2 T A 19: 41,093,420 (GRCm39) R465S possibly damaging Het
Tmem104 G A 11: 115,095,950 (GRCm39) A164T probably damaging Het
Tmem151b A G 17: 45,856,526 (GRCm39) S305P probably damaging Het
Utrn T C 10: 12,625,839 (GRCm39) D114G probably damaging Het
Vmn2r109 A T 17: 20,760,933 (GRCm39) M808K possibly damaging Het
Washc2 T A 6: 116,225,056 (GRCm39) D801E possibly damaging Het
Xkr4 T C 1: 3,286,751 (GRCm39) I480V probably benign Het
Zfp507 G T 7: 35,475,663 (GRCm39) S58* probably null Het
Zfp768 T A 7: 126,943,804 (GRCm39) D108V 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
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
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'- CACTGCTCAAGGTAAAGGCG -3'
(R):5'- GACCTCAGCTAAACCTAGTCTC -3'

Sequencing Primer
(F):5'- CGAGTGTGACAGCCAGCAAC -3'
(R):5'- GGTGTGAGGATAAAACCCTA -3'
Posted On 2016-10-26