Incidental Mutation 'R1777:Mlh3'
ID 197154
Institutional Source Beutler Lab
Gene Symbol Mlh3
Ensembl Gene ENSMUSG00000021245
Gene Name mutL homolog 3
Synonyms
MMRRC Submission 039808-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1777 (G1)
Quality Score 225
Status Not validated
Chromosome 12
Chromosomal Location 85281294-85317373 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 85315528 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Asparagine at position 219 (K219N)
Ref Sequence ENSEMBL: ENSMUSP00000152840 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000008966] [ENSMUST00000019378] [ENSMUST00000117138] [ENSMUST00000121930] [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 possibly damaging
Transcript: ENSMUST00000019378
AA Change: K219N

PolyPhen 2 Score 0.516 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000019378
Gene: ENSMUSG00000021245
AA Change: K219N

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 benign
Transcript: ENSMUST00000121930
SMART Domains Protein: ENSMUSP00000112609
Gene: ENSMUSG00000008822

DomainStartEndE-ValueType
Pfam:Acylphosphatase 64 156 4.5e-25 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000166821
AA Change: K219N

PolyPhen 2 Score 0.516 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000129900
Gene: ENSMUSG00000021245
AA Change: K219N

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 possibly damaging
Transcript: ENSMUST00000220854
AA Change: K219N

PolyPhen 2 Score 0.752 (Sensitivity: 0.85; Specificity: 0.92)
Predicted Effect probably benign
Transcript: ENSMUST00000223230
Coding Region Coverage
  • 1x: 97.4%
  • 3x: 96.8%
  • 10x: 95.1%
  • 20x: 92.1%
Validation Efficiency
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: 91 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930444P10Rik T A 1: 16,148,813 (GRCm39) D111V possibly damaging Het
Ap2a1 G A 7: 44,553,576 (GRCm39) T597M probably damaging Het
Arhgap25 A G 6: 87,440,289 (GRCm39) S364P probably benign Het
Atp6v1a G T 16: 43,935,068 (GRCm39) Y40* probably null Het
Cdh1 T A 8: 107,383,467 (GRCm39) H235Q probably damaging Het
Cntln A G 4: 85,048,916 (GRCm39) E1376G probably benign Het
Cntnap5b T A 1: 100,297,803 (GRCm39) S781T probably benign Het
Cpne4 A G 9: 104,749,887 (GRCm39) T64A probably damaging Het
Ctsg T C 14: 56,338,058 (GRCm39) Y179C probably damaging Het
Cx3cr1 A G 9: 119,880,659 (GRCm39) Y248H probably damaging Het
Dhx37 T C 5: 125,506,995 (GRCm39) E167G probably benign Het
Dnajc21 C A 15: 10,449,693 (GRCm39) A443S probably benign Het
Drd5 T C 5: 38,477,504 (GRCm39) S166P probably damaging Het
Dscaml1 T C 9: 45,595,054 (GRCm39) L719P possibly damaging Het
Eif2ak4 T C 2: 118,261,320 (GRCm39) I542T probably damaging Het
Ephb3 G A 16: 21,035,985 (GRCm39) G291E probably damaging Het
Eva1a T A 6: 82,069,137 (GRCm39) Y155N probably damaging Het
Exog C T 9: 119,278,884 (GRCm39) P189L probably damaging Het
Fam13b A G 18: 34,590,813 (GRCm39) V455A possibly damaging Het
Fmn2 C A 1: 174,409,488 (GRCm39) Q574K unknown Het
Gm6871 A T 7: 41,195,143 (GRCm39) S531R probably benign Het
Golga2 T A 2: 32,195,482 (GRCm39) probably null Het
Hydin C T 8: 111,316,203 (GRCm39) P4365L probably benign Het
Ints8 A T 4: 11,225,600 (GRCm39) probably null Het
Kbtbd12 A C 6: 88,595,042 (GRCm39) S263A probably benign Het
Kcng4 T C 8: 120,360,226 (GRCm39) D50G probably benign Het
Klhl18 A T 9: 110,266,469 (GRCm39) C217S probably benign Het
Klk1b4 A G 7: 43,856,875 (GRCm39) probably benign Het
Klk7 G A 7: 43,462,753 (GRCm39) C186Y probably damaging Het
Krbox5 A T 13: 67,981,984 (GRCm39) R65S probably benign Het
Krit1 T C 5: 3,886,799 (GRCm39) Y635H probably damaging Het
Lipo4 A T 19: 33,476,721 (GRCm39) D342E probably damaging Het
Lsm14b T G 2: 179,673,588 (GRCm39) D199E probably benign Het
Map3k4 A T 17: 12,490,617 (GRCm39) N271K possibly damaging Het
Mast1 T A 8: 85,638,697 (GRCm39) N1544I probably benign Het
Megf6 T A 4: 154,355,147 (GRCm39) C1487* probably null Het
Mtmr4 A G 11: 87,493,656 (GRCm39) K305E probably damaging Het
Myo15a A G 11: 60,405,762 (GRCm39) M3105V probably benign Het
Nbas A T 12: 13,563,563 (GRCm39) I1958F probably benign Het
Nepro A T 16: 44,556,216 (GRCm39) Q458L probably damaging Het
Opa3 T C 7: 18,978,837 (GRCm39) Y101H probably damaging Het
Or11g25 T A 14: 50,723,757 (GRCm39) F281I probably benign Het
Or14c41 T A 7: 86,235,272 (GRCm39) I263N probably benign Het
Or4f15 T A 2: 111,814,042 (GRCm39) I126L possibly damaging Het
Or51f1d T C 7: 102,700,583 (GRCm39) I26T probably benign Het
Or5ac16 A G 16: 59,022,379 (GRCm39) S137P probably benign Het
Or8b12 A G 9: 37,657,607 (GRCm39) Y59C possibly damaging Het
Pate3 T C 9: 35,559,412 (GRCm39) N2D probably benign Het
Pcdhb21 T A 18: 37,648,771 (GRCm39) D633E possibly damaging Het
Pgm2 C T 5: 64,285,125 (GRCm39) P589L probably benign Het
Pigg T A 5: 108,465,257 (GRCm39) D163E probably damaging Het
Polq A G 16: 36,880,586 (GRCm39) T638A possibly damaging Het
Prmt3 T A 7: 49,448,094 (GRCm39) M268K possibly damaging Het
Prmt9 T C 8: 78,291,737 (GRCm39) C370R probably benign Het
Prss57 A T 10: 79,623,219 (GRCm39) V76E possibly damaging Het
Psme3ip1 T C 8: 95,315,439 (GRCm39) E31G probably damaging Het
Pzp T C 6: 128,467,535 (GRCm39) E1089G possibly damaging Het
Qars1 T A 9: 108,385,400 (GRCm39) probably null Het
Ralgapb T C 2: 158,304,115 (GRCm39) Y625H probably damaging Het
Rgl2 G A 17: 34,150,718 (GRCm39) D59N probably benign Het
Robo1 T G 16: 72,801,555 (GRCm39) W1060G probably benign Het
Scaper A T 9: 55,771,830 (GRCm39) V362E probably benign Het
Schip1 T C 3: 68,525,017 (GRCm39) F131S probably damaging Het
Sh2b2 A T 5: 136,256,276 (GRCm39) V252D probably damaging Het
Shld2 C A 14: 33,990,130 (GRCm39) V259L probably benign Het
Slc17a6 A T 7: 51,295,957 (GRCm39) H199L possibly damaging Het
Slc29a1 A G 17: 45,898,234 (GRCm39) Y325H probably damaging Het
Slc29a4 G T 5: 142,699,817 (GRCm39) W156L probably damaging Het
Slc5a3 T A 16: 91,874,644 (GRCm39) S234T probably benign Het
Srd5a3 T G 5: 76,297,630 (GRCm39) V20G probably damaging Het
Stac A T 9: 111,433,150 (GRCm39) S223T possibly damaging Het
Sytl2 A T 7: 90,052,260 (GRCm39) T766S probably benign Het
Tas2r102 A G 6: 132,739,254 (GRCm39) D54G probably benign Het
Tbpl1 A G 10: 22,583,742 (GRCm39) V105A probably damaging Het
Tenm3 G T 8: 48,870,214 (GRCm39) P193Q probably benign Het
Tes G A 6: 17,104,754 (GRCm39) V403M probably benign Het
Tgfbr2 A C 9: 115,938,948 (GRCm39) I318S probably damaging Het
Tgfbr3 C A 5: 107,284,796 (GRCm39) V618L probably benign Het
Tmc1 C T 19: 20,793,473 (GRCm39) probably null Het
Tmem132a G A 19: 10,835,870 (GRCm39) H887Y probably damaging Het
Tmem43 C A 6: 91,454,312 (GRCm39) S33* probably null Het
Tob1 A G 11: 94,104,580 (GRCm39) K39E probably damaging Het
Tut7 A T 13: 59,939,635 (GRCm39) H705Q probably damaging Het
Unc79 T A 12: 103,078,714 (GRCm39) D1433E probably damaging Het
Usp25 T C 16: 76,878,442 (GRCm39) M622T probably damaging Het
Vmn1r158 A T 7: 22,489,855 (GRCm39) L118Q probably damaging Het
Vmn1r217 T A 13: 23,298,495 (GRCm39) I136L probably benign Het
Vmn2r15 A T 5: 109,442,136 (GRCm39) I99K possibly damaging Het
Vwa7 T A 17: 35,243,924 (GRCm39) V786E probably damaging Het
Xkr5 A G 8: 18,989,148 (GRCm39) F248S probably benign Het
Zzef1 A T 11: 72,801,098 (GRCm39) K2444M probably damaging 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
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
R7348:Mlh3 UTSW 12 85,314,215 (GRCm39) missense probably damaging 0.99
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'- CACAGAAAGGGCACTGCACATTG -3'
(R):5'- CCCATGAGGCTGATTTGACCAGAC -3'

Sequencing Primer
(F):5'- GGGCACTGCACATTGATTAC -3'
(R):5'- CTGATTTGACCAGACCAAGTGTG -3'
Posted On 2014-05-23