Incidental Mutation 'PIT4495001:Mlh1'
| ID |
555967 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mlh1
|
| Ensembl Gene |
ENSMUSG00000032498 |
| Gene Name |
mutL homolog 1 |
| Synonyms |
1110035C23Rik, colon cancer, nonpolyposis type 2 |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
PIT4495001 (G1)
|
| Quality Score |
150.008 |
|
Status
|
Not validated
|
| Chromosome |
9 |
| Chromosomal Location |
111057296-111100854 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 111076328 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Phenylalanine
at position 343
(Y343F)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000035079
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000035079]
[ENSMUST00000135218]
[ENSMUST00000135695]
|
| AlphaFold |
Q9JK91 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000035079
AA Change: Y343F
PolyPhen 2
Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
|
| SMART Domains |
Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: Y343F
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
probably benign
Transcript: ENSMUST00000135218
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000135695
|
| SMART Domains |
Protein: ENSMUSP00000119170
Gene: ENSMUSG00000032498
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
|
| Coding Region Coverage |
- 1x: 93.1%
- 3x: 90.6%
- 10x: 84.0%
- 20x: 69.8%
|
| 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: 43 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abl2 |
T |
A |
1: 156,460,755 (GRCm39) |
V384D |
probably damaging |
Het |
| Adamts7 |
A |
G |
9: 90,056,675 (GRCm39) |
E248G |
probably damaging |
Het |
| Aff1 |
A |
G |
5: 103,997,391 (GRCm39) |
T1162A |
probably benign |
Het |
| Ank3 |
C |
A |
10: 69,828,902 (GRCm39) |
H2524N |
|
Het |
| Aoc1l3 |
A |
T |
6: 48,964,710 (GRCm39) |
E239D |
possibly damaging |
Het |
| Cct7 |
T |
A |
6: 85,436,943 (GRCm39) |
N60K |
probably damaging |
Het |
| Cfap43 |
A |
C |
19: 47,885,741 (GRCm39) |
C291W |
probably damaging |
Het |
| Cobl |
G |
A |
11: 12,204,596 (GRCm39) |
T702I |
probably benign |
Het |
| Col5a1 |
C |
A |
2: 27,914,788 (GRCm39) |
Q1624K |
unknown |
Het |
| Cubn |
T |
A |
2: 13,496,561 (GRCm39) |
T22S |
probably benign |
Het |
| Def8 |
A |
C |
8: 124,186,292 (GRCm39) |
M344L |
probably benign |
Het |
| Fzd7 |
A |
G |
1: 59,523,466 (GRCm39) |
T450A |
probably benign |
Het |
| Gm11214 |
G |
A |
4: 63,580,922 (GRCm39) |
L76F |
probably benign |
Het |
| Gm5797 |
T |
C |
14: 7,329,530 (GRCm38) |
T153A |
probably benign |
Het |
| Gsk3a |
A |
C |
7: 24,935,064 (GRCm39) |
S129A |
probably damaging |
Het |
| Intu |
A |
G |
3: 40,652,033 (GRCm39) |
Q830R |
probably benign |
Het |
| Kcnma1 |
C |
T |
14: 23,475,665 (GRCm39) |
V750I |
probably benign |
Het |
| Myb |
C |
T |
10: 21,028,521 (GRCm39) |
R114H |
probably damaging |
Het |
| Neb |
A |
T |
2: 52,102,748 (GRCm39) |
D4508E |
probably benign |
Het |
| Nell2 |
T |
C |
15: 95,281,608 (GRCm39) |
D366G |
probably benign |
Het |
| Or1o3 |
A |
C |
17: 37,573,721 (GRCm39) |
V278G |
possibly damaging |
Het |
| Or4d6 |
A |
G |
19: 12,086,076 (GRCm39) |
I52T |
possibly damaging |
Het |
| Or5ac25 |
A |
C |
16: 59,181,871 (GRCm39) |
F237V |
probably damaging |
Het |
| Or5h26 |
G |
T |
16: 58,988,337 (GRCm39) |
H56Q |
possibly damaging |
Het |
| Or7a38 |
T |
C |
10: 78,752,821 (GRCm39) |
V49A |
probably benign |
Het |
| Pcdhgc5 |
C |
T |
18: 37,954,030 (GRCm39) |
H435Y |
possibly damaging |
Het |
| Pira12 |
A |
T |
7: 3,900,457 (GRCm39) |
C98S |
probably damaging |
Het |
| Pnpla7 |
T |
A |
2: 24,932,151 (GRCm39) |
D935E |
probably damaging |
Het |
| Pole |
A |
G |
5: 110,451,780 (GRCm39) |
E874G |
probably damaging |
Het |
| Psd3 |
A |
C |
8: 68,416,565 (GRCm39) |
I158R |
probably benign |
Het |
| Pzp |
C |
A |
6: 128,479,192 (GRCm39) |
V654L |
probably benign |
Het |
| Rabep1 |
A |
G |
11: 70,808,405 (GRCm39) |
T454A |
probably damaging |
Het |
| Rad54l2 |
C |
A |
9: 106,593,343 (GRCm39) |
S419I |
probably benign |
Het |
| Rin3 |
A |
G |
12: 102,335,295 (GRCm39) |
D402G |
probably benign |
Het |
| Ripk4 |
T |
C |
16: 97,544,370 (GRCm39) |
H759R |
probably damaging |
Het |
| Rlig1 |
A |
T |
10: 100,419,812 (GRCm39) |
F90I |
probably damaging |
Het |
| Sbsn |
GAAAAGGAAGCAGAAAAAGTGGCCCATGGGGTACAGAATGGAGTCAACCAGGCTCAAAAGGAAGCAGAAAAAGTGGCCCATGGGGTACAGAATGGAGTCAACCAGGCTCAAAAGGAAGCAGAAAAAGTGGCCCATGGGGTACAGAATGGAGTCAACCAGGCTCAAAAGGAAGCAGAAAAAGTGGCCCA |
GAAAAGGAAGCAGAAAAAGTGGCCCATGGGGTACAGAATGGAGTCAACCAGGCTCAAAAGGAAGCAGAAAAAGTGGCCCATGGGGTACAGAATGGAGTCAACCAGGCTCAAAAGGAAGCAGAAAAAGTGGCCCA |
7: 30,452,391 (GRCm39) |
|
probably benign |
Het |
| Sf3a3 |
C |
T |
4: 124,622,113 (GRCm39) |
P391L |
probably damaging |
Het |
| Snx9 |
T |
A |
17: 5,970,401 (GRCm39) |
I379K |
possibly damaging |
Het |
| Syt5 |
A |
C |
7: 4,544,077 (GRCm39) |
|
probably null |
Het |
| Tex47 |
A |
G |
5: 7,355,011 (GRCm39) |
D64G |
probably benign |
Het |
| Zbbx |
C |
A |
3: 74,968,944 (GRCm39) |
W509L |
probably damaging |
Het |
| Zer1 |
T |
C |
2: 29,993,555 (GRCm39) |
K551R |
probably benign |
Het |
|
| Other mutations in Mlh1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
R5602:Mlh1
|
UTSW |
9 |
111,081,946 (GRCm39) |
missense |
probably damaging |
0.97 |
|
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'- GCATGACCTGTGCACATGTG -3'
(R):5'- TTGTCTAGTCGCCACATGTC -3'
Sequencing Primer
(F):5'- TGGAACACACAGACATAGACACAGAG -3'
(R):5'- TCTAGTCGCCACATGTCACCAC -3'
|
| Posted On |
2019-06-07 |
Incidental Mutation