Incidental Mutation 'R7348:Mlh3'
ID 570376
Institutional Source Beutler Lab
Gene Symbol Mlh3
Ensembl Gene ENSMUSG00000021245
Gene Name mutL homolog 3
Synonyms
MMRRC Submission 045380-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R7348 (G1)
Quality Score 225.009
Status Validated
Chromosome 12
Chromosomal Location 85281294-85317373 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 85314215 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Proline to Glutamine at position 657 (P657Q)
Ref Sequence ENSEMBL: ENSMUSP00000019378 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000008966] [ENSMUST00000019378] [ENSMUST00000117138] [ENSMUST00000166821] [ENSMUST00000220854] [ENSMUST00000223230]
AlphaFold A0A1Y7VMP7
Predicted Effect probably benign
Transcript: ENSMUST00000008966
SMART Domains Protein: ENSMUSP00000008966
Gene: ENSMUSG00000008822

DomainStartEndE-ValueType
Pfam:Acylphosphatase 1 98 6e-26 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000019378
AA Change: P657Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000019378
Gene: ENSMUSG00000021245
AA Change: P657Q

DomainStartEndE-ValueType
HATPase_c 17 125 1.04e0 SMART
DNA_mis_repair 211 349 8.78e-22 SMART
low complexity region 582 594 N/A INTRINSIC
low complexity region 658 671 N/A INTRINSIC
low complexity region 863 882 N/A INTRINSIC
low complexity region 1078 1096 N/A INTRINSIC
MutL_C 1153 1334 7.45e-28 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000117138
SMART Domains Protein: ENSMUSP00000113161
Gene: ENSMUSG00000008822

DomainStartEndE-ValueType
Pfam:Acylphosphatase 1 98 6e-26 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000166821
AA Change: P657Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000129900
Gene: ENSMUSG00000021245
AA Change: P657Q

DomainStartEndE-ValueType
HATPase_c 17 125 1.04e0 SMART
DNA_mis_repair 211 349 8.78e-22 SMART
low complexity region 582 594 N/A INTRINSIC
low complexity region 658 671 N/A INTRINSIC
low complexity region 863 882 N/A INTRINSIC
low complexity region 1078 1096 N/A INTRINSIC
MutL_C 1153 1334 7.45e-28 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000220854
AA Change: P657Q

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
Predicted Effect probably benign
Transcript: ENSMUST00000223230
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 98.8%
Validation Efficiency 99% (80/81)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for a targeted null mutation are sterile. Both oocytes and spermatocytes exhibit meiotic block and die. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 79 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abra G A 15: 41,729,555 (GRCm39) R282C probably damaging Het
Adcy2 T A 13: 68,882,794 (GRCm39) E314D possibly damaging Het
Adgrl2 A T 3: 148,523,402 (GRCm39) I274N Het
Adpgk A G 9: 59,221,069 (GRCm39) I292V probably benign Het
Agtrap G T 4: 148,165,054 (GRCm39) F124L probably benign Het
Ankrd26 A G 6: 118,485,525 (GRCm39) Y1450H probably damaging Het
Ap4e1 A T 2: 126,903,896 (GRCm39) S933C probably damaging Het
Ap4e1 G T 2: 126,903,897 (GRCm39) S933I possibly damaging Het
Ap5s1 A T 2: 131,054,572 (GRCm39) T128S possibly damaging Het
Arih1 T C 9: 59,393,341 (GRCm39) Y97C probably damaging Het
Atp1a3 A G 7: 24,678,251 (GRCm39) F1034S unknown Het
Bmp6 T C 13: 38,669,879 (GRCm39) S388P probably benign Het
Ccdc39 A G 3: 33,886,825 (GRCm39) V261A possibly damaging Het
Ccdc66 C T 14: 27,222,293 (GRCm39) C150Y probably damaging Het
Cep89 G A 7: 35,129,353 (GRCm39) R630H probably damaging Het
Cln6 A G 9: 62,756,458 (GRCm39) S201G probably benign Het
Cntnap4 T C 8: 113,391,909 (GRCm39) Y125H probably damaging Het
Copa A G 1: 171,929,790 (GRCm39) T286A possibly damaging Het
Cul9 A T 17: 46,821,919 (GRCm39) I1852K possibly damaging Het
Cyp2j8 C A 4: 96,332,877 (GRCm39) A490S probably benign Het
Cyp2t4 A G 7: 26,856,676 (GRCm39) I239V probably benign Het
Dpcd A G 19: 45,560,905 (GRCm39) Y111C probably damaging Het
E2f7 C T 10: 110,616,836 (GRCm39) T692I probably damaging Het
Fastkd5 A G 2: 130,457,055 (GRCm39) Y512H probably damaging Het
Fastkd5 A C 2: 130,458,359 (GRCm39) M77R probably benign Het
Fhod3 A G 18: 25,223,524 (GRCm39) R957G possibly damaging Het
H6pd C A 4: 150,068,359 (GRCm39) probably null Het
Haus5 G T 7: 30,356,391 (GRCm39) P544Q possibly damaging Het
Ifi207 CTGTTGATGAAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATACAGTTGCTTGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATAGAGTTGCATATGGAGCCAGGAGGATGCTATATGTTGTTGATGAAGTTGCATGTGGAGCCAGGAG CTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATACAGTTGCTTGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATAGAGTTGCATATGGAGCCAGGAGGATGCTATATGTTGTTGATGAAGTTGCATGTGGAGCCAGGAG 1: 173,556,762 (GRCm39) probably benign Het
Igf2r A G 17: 12,922,371 (GRCm39) Y1248H probably damaging Het
Izumo3 T C 4: 92,035,455 (GRCm39) N6S possibly damaging Het
Lrp6 G T 6: 134,427,781 (GRCm39) P1604T probably damaging Het
Map3k8 T A 18: 4,340,561 (GRCm39) H251L probably damaging Het
Mapre3 T C 5: 31,019,173 (GRCm39) Y6H probably benign Het
Mrgpra1 T C 7: 46,985,157 (GRCm39) Y174C probably benign Het
Ms4a6d G A 19: 11,567,437 (GRCm39) Q155* probably null Het
Myh1 C A 11: 67,093,365 (GRCm39) P152Q probably damaging Het
Myh6 A T 14: 55,189,716 (GRCm39) L1110Q probably damaging Het
Nf1 T A 11: 79,427,676 (GRCm39) S1778T probably benign Het
Nkpd1 G A 7: 19,258,341 (GRCm39) E707K probably damaging Het
Nlrp4a A G 7: 26,143,698 (GRCm39) E21G probably damaging Het
Nr4a3 T G 4: 48,051,290 (GRCm39) S15A possibly damaging Het
Or2f1 T C 6: 42,721,790 (GRCm39) L273S possibly damaging Het
Or5p1 T C 7: 107,916,920 (GRCm39) V273A possibly damaging Het
Or5p64 T C 7: 107,855,330 (GRCm39) D5G probably benign Het
Or7a38 A G 10: 78,753,396 (GRCm39) T241A probably damaging Het
Parg G A 14: 31,972,036 (GRCm39) R677Q possibly damaging Het
Pcsk5 A T 19: 17,434,182 (GRCm39) C1395* probably null Het
Psd2 G A 18: 36,113,389 (GRCm39) S287N possibly damaging Het
Psd3 T C 8: 68,243,583 (GRCm39) N685S possibly damaging Het
Pygb C T 2: 150,628,903 (GRCm39) T39M probably benign Het
Rbfox1 C A 16: 7,225,888 (GRCm39) Y351* probably null Het
Rftn1 A G 17: 50,311,351 (GRCm39) L396P probably damaging Het
S1pr1 A G 3: 115,505,710 (GRCm39) Y295H probably damaging Het
Scn5a T C 9: 119,364,899 (GRCm39) M440V probably benign Het
Sel1l2 T C 2: 140,107,644 (GRCm39) N240S probably benign Het
Skic3 T C 13: 76,331,003 (GRCm39) F1478L possibly damaging Het
Skint1 T C 4: 111,878,770 (GRCm39) L234P probably damaging Het
Skint11 T A 4: 114,101,919 (GRCm39) Y311N probably benign Het
Slc6a5 A T 7: 49,559,915 (GRCm39) probably benign Het
Tas2r134 T C 2: 51,518,414 (GRCm39) S298P possibly damaging Het
Tbcd C A 11: 121,485,137 (GRCm39) A773D probably benign Het
Tgoln1 G C 6: 72,593,261 (GRCm39) T73R probably benign Het
Tmem184a T C 5: 139,799,809 (GRCm39) E24G probably null Het
Tmem207 C A 16: 26,335,577 (GRCm39) W53C possibly damaging Het
Tns1 T A 1: 73,956,076 (GRCm39) H549L possibly damaging Het
Ttc41 G T 10: 86,586,212 (GRCm39) E839* probably null Het
Ufd1 T G 16: 18,634,635 (GRCm39) probably benign Het
Usp28 A G 9: 48,942,177 (GRCm39) E713G probably benign Het
Utrn A G 10: 12,623,762 (GRCm39) W159R probably damaging Het
Vcl C T 14: 21,053,218 (GRCm39) A411V probably benign Het
Vcl T A 14: 21,059,020 (GRCm39) C545* probably null Het
Vmn1r120 A T 7: 20,787,377 (GRCm39) S111R probably damaging Het
Wwox T A 8: 115,199,392 (GRCm39) C146S probably benign Het
Zbtb2 T C 10: 4,324,574 (GRCm39) T57A possibly damaging Het
Zfp362 T C 4: 128,671,010 (GRCm39) D336G possibly damaging Het
Zfp628 G A 7: 4,924,817 (GRCm39) G1013E probably damaging Het
Zfp704 A G 3: 9,539,658 (GRCm39) S231P probably damaging Het
Zhx3 G T 2: 160,624,038 (GRCm39) S43* probably null Het
Other mutations in Mlh3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01402:Mlh3 APN 12 85,314,703 (GRCm39) missense probably benign
IGL01462:Mlh3 APN 12 85,313,510 (GRCm39) missense probably benign
IGL01961:Mlh3 APN 12 85,313,118 (GRCm39) missense probably benign 0.00
IGL02596:Mlh3 APN 12 85,287,732 (GRCm39) critical splice donor site probably null
IGL03008:Mlh3 APN 12 85,287,625 (GRCm39) missense probably benign 0.23
IGL03142:Mlh3 APN 12 85,297,075 (GRCm39) critical splice donor site probably null
R0032:Mlh3 UTSW 12 85,292,523 (GRCm39) intron probably benign
R0032:Mlh3 UTSW 12 85,292,523 (GRCm39) intron probably benign
R0078:Mlh3 UTSW 12 85,315,592 (GRCm39) missense probably damaging 0.98
R0129:Mlh3 UTSW 12 85,312,914 (GRCm39) splice site probably benign
R0269:Mlh3 UTSW 12 85,315,179 (GRCm39) missense probably benign 0.00
R0393:Mlh3 UTSW 12 85,314,361 (GRCm39) nonsense probably null
R0403:Mlh3 UTSW 12 85,315,742 (GRCm39) missense possibly damaging 0.93
R0409:Mlh3 UTSW 12 85,287,628 (GRCm39) missense possibly damaging 0.95
R0587:Mlh3 UTSW 12 85,313,193 (GRCm39) missense probably benign 0.00
R0701:Mlh3 UTSW 12 85,314,677 (GRCm39) missense probably benign 0.00
R0718:Mlh3 UTSW 12 85,294,471 (GRCm39) missense possibly damaging 0.86
R0883:Mlh3 UTSW 12 85,282,488 (GRCm39) missense possibly damaging 0.89
R0989:Mlh3 UTSW 12 85,316,169 (GRCm39) missense probably benign 0.22
R0990:Mlh3 UTSW 12 85,314,539 (GRCm39) missense probably benign
R1467:Mlh3 UTSW 12 85,284,374 (GRCm39) nonsense probably null
R1467:Mlh3 UTSW 12 85,284,374 (GRCm39) nonsense probably null
R1562:Mlh3 UTSW 12 85,313,694 (GRCm39) missense probably benign 0.14
R1599:Mlh3 UTSW 12 85,315,143 (GRCm39) missense probably damaging 1.00
R1694:Mlh3 UTSW 12 85,313,915 (GRCm39) missense probably damaging 1.00
R1777:Mlh3 UTSW 12 85,315,528 (GRCm39) missense possibly damaging 0.75
R1822:Mlh3 UTSW 12 85,312,919 (GRCm39) splice site probably benign
R1874:Mlh3 UTSW 12 85,284,287 (GRCm39) critical splice donor site probably null
R1914:Mlh3 UTSW 12 85,308,442 (GRCm39) missense probably benign 0.08
R1915:Mlh3 UTSW 12 85,308,442 (GRCm39) missense probably benign 0.08
R2075:Mlh3 UTSW 12 85,315,915 (GRCm39) nonsense probably null
R2083:Mlh3 UTSW 12 85,315,815 (GRCm39) missense probably benign 0.16
R2267:Mlh3 UTSW 12 85,307,585 (GRCm39) missense possibly damaging 0.55
R2334:Mlh3 UTSW 12 85,314,851 (GRCm39) missense probably benign 0.00
R2882:Mlh3 UTSW 12 85,314,340 (GRCm39) missense probably damaging 1.00
R3623:Mlh3 UTSW 12 85,315,169 (GRCm39) missense probably damaging 1.00
R3624:Mlh3 UTSW 12 85,315,169 (GRCm39) missense probably damaging 1.00
R3963:Mlh3 UTSW 12 85,315,454 (GRCm39) missense possibly damaging 0.94
R4376:Mlh3 UTSW 12 85,305,972 (GRCm39) missense probably benign 0.00
R5334:Mlh3 UTSW 12 85,292,535 (GRCm39) critical splice donor site probably null
R5526:Mlh3 UTSW 12 85,316,147 (GRCm39) nonsense probably null
R5556:Mlh3 UTSW 12 85,315,267 (GRCm39) nonsense probably null
R5611:Mlh3 UTSW 12 85,314,219 (GRCm39) missense probably benign 0.21
R5911:Mlh3 UTSW 12 85,315,229 (GRCm39) missense probably damaging 1.00
R6050:Mlh3 UTSW 12 85,287,620 (GRCm39) missense possibly damaging 0.89
R6221:Mlh3 UTSW 12 85,315,192 (GRCm39) missense possibly damaging 0.94
R6377:Mlh3 UTSW 12 85,315,271 (GRCm39) missense probably damaging 0.97
R6820:Mlh3 UTSW 12 85,294,497 (GRCm39) missense probably damaging 1.00
R6826:Mlh3 UTSW 12 85,292,598 (GRCm39) missense probably benign 0.38
R6992:Mlh3 UTSW 12 85,282,494 (GRCm39) missense probably damaging 1.00
R7217:Mlh3 UTSW 12 85,313,481 (GRCm39) missense probably benign
R7228:Mlh3 UTSW 12 85,282,430 (GRCm39) missense probably benign 0.07
R7599:Mlh3 UTSW 12 85,314,973 (GRCm39) nonsense probably null
R7722:Mlh3 UTSW 12 85,314,266 (GRCm39) missense probably benign 0.01
R7762:Mlh3 UTSW 12 85,315,058 (GRCm39) missense possibly damaging 0.63
R7786:Mlh3 UTSW 12 85,313,511 (GRCm39) missense probably benign 0.00
R8231:Mlh3 UTSW 12 85,307,572 (GRCm39) critical splice donor site probably null
R8415:Mlh3 UTSW 12 85,315,854 (GRCm39) missense probably benign 0.35
R8750:Mlh3 UTSW 12 85,308,488 (GRCm39) missense probably damaging 0.99
R8794:Mlh3 UTSW 12 85,282,497 (GRCm39) missense probably damaging 1.00
R9301:Mlh3 UTSW 12 85,292,613 (GRCm39) missense possibly damaging 0.77
R9385:Mlh3 UTSW 12 85,316,144 (GRCm39) missense probably damaging 1.00
R9518:Mlh3 UTSW 12 85,313,004 (GRCm39) missense probably benign 0.00
R9549:Mlh3 UTSW 12 85,313,249 (GRCm39) missense probably benign 0.01
RF014:Mlh3 UTSW 12 85,314,803 (GRCm39) missense probably benign
X0024:Mlh3 UTSW 12 85,294,443 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TCTACACCATGGGAAGGAGG -3'
(R):5'- AAAGGAGCCCAGTAGTCGTG -3'

Sequencing Primer
(F):5'- CCATGGGAAGGAGGATGCATC -3'
(R):5'- CCCAGTAGTCGTGGAAGAGTAAATG -3'
Posted On 2019-09-13