Incidental Mutation 'R6820:Mlh3'
ID 537581
Institutional Source Beutler Lab
Gene Symbol Mlh3
Ensembl Gene ENSMUSG00000021245
Gene Name mutL homolog 3
Synonyms
MMRRC Submission 044932-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R6820 (G1)
Quality Score 225.009
Status Validated
Chromosome 12
Chromosomal Location 85281294-85317373 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 85294497 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 1233 (D1233G)
Ref Sequence ENSEMBL: ENSMUSP00000152840 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000019378] [ENSMUST00000166821] [ENSMUST00000220854] [ENSMUST00000223230]
AlphaFold A0A1Y7VMP7
Predicted Effect probably damaging
Transcript: ENSMUST00000019378
AA Change: D1201G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000019378
Gene: ENSMUSG00000021245
AA Change: D1201G

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: ENSMUST00000166821
AA Change: D1201G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000129900
Gene: ENSMUSG00000021245
AA Change: D1201G

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: D1233G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect probably damaging
Transcript: ENSMUST00000223230
AA Change: D159G

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
Meta Mutation Damage Score 0.5214 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.7%
Validation Efficiency 98% (46/47)
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: 46 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Accs T A 2: 93,673,266 (GRCm39) N141Y probably null Het
Chkb A G 15: 89,312,379 (GRCm39) L46P probably damaging Het
Col9a3 G A 2: 180,248,927 (GRCm39) V260M probably damaging Het
Dna2 T C 10: 62,800,683 (GRCm39) I739T possibly damaging Het
Dnah17 T C 11: 117,959,826 (GRCm39) H2620R probably damaging Het
Dsel A G 1: 111,787,547 (GRCm39) V996A probably damaging Het
Dst T C 1: 34,250,337 (GRCm39) L1757S probably damaging Het
Exoc5 A T 14: 49,286,387 (GRCm39) probably null Het
Fam120a A T 13: 49,034,468 (GRCm39) V1048E possibly damaging Het
Fam50b G A 13: 34,931,084 (GRCm39) E187K possibly damaging Het
Fbxw19 T A 9: 109,311,079 (GRCm39) T377S probably benign Het
Fbxw28 A T 9: 109,167,493 (GRCm39) F88Y probably damaging Het
Grik5 C T 7: 24,745,780 (GRCm39) R431Q possibly damaging Het
Gtsf1 T C 15: 103,328,954 (GRCm39) T92A probably benign Het
Hoxc13 A G 15: 102,830,257 (GRCm39) Y212C probably damaging Het
Itih2 T C 2: 10,102,909 (GRCm39) I742V probably benign Het
Kat7 T C 11: 95,174,965 (GRCm39) T351A probably damaging Het
Mroh2b A G 15: 4,982,756 (GRCm39) D1525G probably damaging Het
Nme5 T C 18: 34,704,626 (GRCm39) Y73C probably damaging Het
Nr3c2 T C 8: 77,969,086 (GRCm39) V957A probably damaging Het
Nup153 A G 13: 46,863,459 (GRCm39) S301P probably benign Het
Obscn T C 11: 58,942,019 (GRCm39) D5013G probably damaging Het
Or4f54 C T 2: 111,123,455 (GRCm39) P281S probably damaging Het
Or5p51 A G 7: 107,444,298 (GRCm39) V214A probably benign Het
Or8g51 A G 9: 38,608,771 (GRCm39) V297A possibly damaging Het
Pak1 A G 7: 97,535,586 (GRCm39) N226D probably benign Het
Pak4 A G 7: 28,262,461 (GRCm39) Y384H probably benign Het
Pkp3 T C 7: 140,659,757 (GRCm39) probably null Het
Prxl2b A T 4: 154,982,623 (GRCm39) D50E probably damaging Het
Psd G T 19: 46,309,283 (GRCm39) A558E probably damaging Het
Psmd14 C A 2: 61,607,068 (GRCm39) H172N probably benign Het
Pygb G T 2: 150,658,674 (GRCm39) W366L possibly damaging Het
Rbm39 A T 2: 156,021,146 (GRCm39) M1K probably null Het
Rnf213 T C 11: 119,339,664 (GRCm39) I3421T probably damaging Het
Rsf1 ATGGCG ATGGCGACGGTGGCG 7: 97,229,111 (GRCm39) probably benign Het
Smg6 T C 11: 74,932,790 (GRCm39) V88A probably damaging Het
Tha1 T C 11: 117,762,504 (GRCm39) E80G probably benign Het
Tie1 A G 4: 118,341,583 (GRCm39) V243A probably damaging Het
Tmem215 T C 4: 40,473,926 (GRCm39) M1T probably null Het
Tpm2 A G 4: 43,518,443 (GRCm39) Y221H probably damaging Het
Ubap1 C T 4: 41,379,854 (GRCm39) P356L probably benign Het
Wbp2nl G T 15: 82,197,996 (GRCm39) A178S possibly damaging Het
Wdr54 A T 6: 83,131,601 (GRCm39) S139T probably benign Het
Wipi2 G C 5: 142,615,555 (GRCm39) Q14H probably benign Het
Zan T C 5: 137,406,106 (GRCm39) probably benign Het
Zfp735 A G 11: 73,579,783 (GRCm39) M1V 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
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'- TGCTGGAAAACATTACCAGGG -3'
(R):5'- TCAAGTGGCTGACTGTCCCTTAG -3'

Sequencing Primer
(F):5'- ACTGCTAACCGTTAAGACCTTGGG -3'
(R):5'- GGCTGACTGTCCCTTAGTTTGC -3'
Posted On 2018-10-18