Incidental Mutation 'R1599:Mlh3'
| ID |
176063 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mlh3
|
| Ensembl Gene |
ENSMUSG00000021245 |
| Gene Name |
mutL homolog 3 |
| Synonyms |
|
| MMRRC Submission |
039636-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R1599 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
12 |
| Chromosomal Location |
85281294-85317373 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 85315143 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Isoleucine
at position 348
(L348I)
|
| 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
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Acylphosphatase
|
1 |
98 |
6e-26 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000019378
AA Change: L348I
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000019378
Gene: ENSMUSG00000021245
AA Change: L348I
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Acylphosphatase
|
1 |
98 |
6e-26 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000121930
|
| SMART Domains |
Protein: ENSMUSP00000112609
Gene: ENSMUSG00000008822
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Acylphosphatase
|
64 |
156 |
4.5e-25 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000166821
AA Change: L348I
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000129900
Gene: ENSMUSG00000021245
AA Change: L348I
| Domain | Start | End | E-Value | Type |
|---|
|
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: L348I
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000223230
|
| Coding Region Coverage |
- 1x: 99.0%
- 3x: 98.0%
- 10x: 95.2%
- 20x: 88.9%
|
| 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: 75 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2700049A03Rik |
A |
G |
12: 71,197,033 (GRCm39) |
E202G |
probably damaging |
Het |
| Adam23 |
A |
G |
1: 63,610,092 (GRCm39) |
D698G |
possibly damaging |
Het |
| Adam3 |
T |
C |
8: 25,215,377 (GRCm39) |
D20G |
possibly damaging |
Het |
| Adamts12 |
T |
C |
15: 11,071,797 (GRCm39) |
S114P |
probably damaging |
Het |
| Adgrg6 |
T |
A |
10: 14,343,057 (GRCm39) |
R297* |
probably null |
Het |
| Ahdc1 |
A |
T |
4: 132,792,247 (GRCm39) |
S1163C |
possibly damaging |
Het |
| Axl |
A |
G |
7: 25,463,394 (GRCm39) |
Y619H |
probably damaging |
Het |
| Bcl11a |
G |
T |
11: 24,113,887 (GRCm39) |
C410F |
probably damaging |
Het |
| Brca2 |
C |
A |
5: 150,472,178 (GRCm39) |
S2359* |
probably null |
Het |
| Calca |
A |
G |
7: 114,233,707 (GRCm39) |
S75P |
probably damaging |
Het |
| Ccn2 |
A |
T |
10: 24,473,297 (GRCm39) |
R279W |
probably benign |
Het |
| Ccpg1 |
T |
A |
9: 72,906,407 (GRCm39) |
Y54* |
probably null |
Het |
| Cfap161 |
A |
T |
7: 83,425,287 (GRCm39) |
M268K |
possibly damaging |
Het |
| Cfap61 |
T |
A |
2: 145,854,083 (GRCm39) |
V365E |
probably benign |
Het |
| Cgnl1 |
T |
C |
9: 71,548,709 (GRCm39) |
I1000V |
probably benign |
Het |
| Chd2 |
A |
T |
7: 73,122,799 (GRCm39) |
D978E |
probably benign |
Het |
| Cyth1 |
G |
A |
11: 118,068,047 (GRCm39) |
T297M |
probably damaging |
Het |
| Dennd1b |
T |
G |
1: 139,095,468 (GRCm39) |
D505E |
probably benign |
Het |
| Dgkd |
A |
G |
1: 87,809,608 (GRCm39) |
T99A |
possibly damaging |
Het |
| Fam161a |
A |
T |
11: 22,971,093 (GRCm39) |
M180L |
probably benign |
Het |
| Gar1 |
G |
T |
3: 129,624,253 (GRCm39) |
R80S |
probably benign |
Het |
| Gm28042 |
T |
C |
2: 119,866,944 (GRCm39) |
S419P |
probably benign |
Het |
| Gm5591 |
A |
C |
7: 38,219,794 (GRCm39) |
C360G |
probably benign |
Het |
| Golga2 |
A |
G |
2: 32,193,185 (GRCm39) |
H427R |
probably benign |
Het |
| Gpt2 |
A |
G |
8: 86,238,863 (GRCm39) |
Y232C |
probably damaging |
Het |
| Hnrnpll |
T |
A |
17: 80,361,054 (GRCm39) |
H118L |
unknown |
Het |
| Ice2 |
T |
A |
9: 69,318,724 (GRCm39) |
C303S |
probably null |
Het |
| Ikzf3 |
C |
A |
11: 98,357,919 (GRCm39) |
G473C |
probably damaging |
Het |
| Kansl3 |
A |
T |
1: 36,406,951 (GRCm39) |
D38E |
probably damaging |
Het |
| Kcna6 |
A |
T |
6: 126,716,282 (GRCm39) |
D202E |
probably benign |
Het |
| Klhl21 |
G |
A |
4: 152,096,757 (GRCm39) |
G341D |
probably damaging |
Het |
| Klhl29 |
A |
T |
12: 5,143,538 (GRCm39) |
V497D |
probably damaging |
Het |
| Kmt2b |
G |
A |
7: 30,270,000 (GRCm39) |
L2449F |
probably damaging |
Het |
| Kmt5c |
A |
G |
7: 4,744,899 (GRCm39) |
E10G |
probably damaging |
Het |
| Lama3 |
C |
T |
18: 12,583,457 (GRCm39) |
Q682* |
probably null |
Het |
| Lamb3 |
T |
C |
1: 193,002,801 (GRCm39) |
V82A |
probably damaging |
Het |
| Larp4b |
C |
T |
13: 9,172,186 (GRCm39) |
T2I |
probably damaging |
Het |
| Man2a1 |
T |
C |
17: 64,986,826 (GRCm39) |
Y613H |
possibly damaging |
Het |
| Mcm3 |
G |
A |
1: 20,890,422 (GRCm39) |
T4I |
probably benign |
Het |
| Mki67 |
C |
T |
7: 135,301,663 (GRCm39) |
A1124T |
probably benign |
Het |
| Mmrn1 |
G |
A |
6: 60,922,021 (GRCm39) |
M159I |
probably benign |
Het |
| Muc5ac |
A |
T |
7: 141,352,640 (GRCm39) |
Q709L |
possibly damaging |
Het |
| Naip2 |
C |
T |
13: 100,298,489 (GRCm39) |
A516T |
possibly damaging |
Het |
| Nosip |
A |
G |
7: 44,723,430 (GRCm39) |
N32S |
probably benign |
Het |
| Npat |
T |
C |
9: 53,473,704 (GRCm39) |
Y499H |
possibly damaging |
Het |
| Nt5c1b |
T |
A |
12: 10,440,024 (GRCm39) |
I522N |
probably damaging |
Het |
| Or1j18 |
G |
T |
2: 36,625,001 (GRCm39) |
V223F |
probably benign |
Het |
| Or2r3 |
T |
A |
6: 42,448,176 (GRCm39) |
K312M |
probably damaging |
Het |
| Or52d3 |
A |
G |
7: 104,228,855 (GRCm39) |
M1V |
probably null |
Het |
| Or7g32 |
T |
A |
9: 19,389,517 (GRCm39) |
T7S |
probably damaging |
Het |
| Pappa2 |
A |
G |
1: 158,684,742 (GRCm39) |
F799S |
probably damaging |
Het |
| Pate5 |
T |
C |
9: 35,750,333 (GRCm39) |
N113S |
probably benign |
Het |
| Pcdha1 |
C |
T |
18: 37,318,290 (GRCm39) |
T941M |
probably damaging |
Het |
| Pilrb2 |
A |
T |
5: 137,866,859 (GRCm39) |
F215I |
possibly damaging |
Het |
| Pkd1l3 |
G |
T |
8: 110,363,016 (GRCm39) |
M1092I |
probably benign |
Het |
| Ppp1r21 |
G |
T |
17: 88,880,055 (GRCm39) |
V491L |
probably benign |
Het |
| Prickle2 |
T |
C |
6: 92,387,855 (GRCm39) |
T516A |
probably benign |
Het |
| Prr27 |
G |
T |
5: 87,991,084 (GRCm39) |
R232L |
probably benign |
Het |
| Rab3gap2 |
C |
T |
1: 184,983,223 (GRCm39) |
T454I |
probably benign |
Het |
| Rgs11 |
C |
A |
17: 26,427,223 (GRCm39) |
H385N |
probably damaging |
Het |
| S1pr5 |
T |
A |
9: 21,155,230 (GRCm39) |
T399S |
probably benign |
Het |
| Sacs |
G |
A |
14: 61,441,087 (GRCm39) |
M1044I |
probably benign |
Het |
| Sec31b |
T |
A |
19: 44,511,592 (GRCm39) |
Q603L |
possibly damaging |
Het |
| Setx |
G |
A |
2: 29,030,385 (GRCm39) |
E275K |
probably benign |
Het |
| Sh3tc1 |
G |
A |
5: 35,864,856 (GRCm39) |
P444S |
probably benign |
Het |
| Shoc1 |
A |
T |
4: 59,072,349 (GRCm39) |
N622K |
possibly damaging |
Het |
| Strn3 |
T |
A |
12: 51,699,549 (GRCm39) |
N208Y |
possibly damaging |
Het |
| Tmem87a |
T |
C |
2: 120,224,868 (GRCm39) |
N131S |
probably damaging |
Het |
| Tmprss13 |
T |
A |
9: 45,249,616 (GRCm39) |
W318R |
probably damaging |
Het |
| Trabd2b |
T |
C |
4: 114,266,178 (GRCm39) |
V64A |
probably damaging |
Het |
| Trafd1 |
A |
T |
5: 121,517,720 (GRCm39) |
N24K |
probably damaging |
Het |
| Ttc41 |
T |
C |
10: 86,612,437 (GRCm39) |
S1237P |
probably benign |
Het |
| Ttll1 |
A |
G |
15: 83,381,555 (GRCm39) |
V238A |
probably benign |
Het |
| Vps50 |
T |
C |
6: 3,565,537 (GRCm39) |
S492P |
probably benign |
Het |
| Zic1 |
T |
C |
9: 91,243,741 (GRCm39) |
I409V |
probably benign |
Het |
|
| Other mutations in Mlh3 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
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'- TTACACGCTTCCCGGAAACTGCTC -3'
(R):5'- GGCTACATCAGCTCTGAAGCACAC -3'
Sequencing Primer
(F):5'- GGAAACTGCTCTGGTCACAC -3'
(R):5'- GCTCTGCCAGTAGGCAAATG -3'
|
| Posted On |
2014-04-24 |
Incidental Mutation