Mutagenetix > Incidental Mutation

Incidental Mutation 'R0587:Mlh3'

55819

Institutional Source

Beutler Lab

Gene Symbol

Mlh3

Ensembl Gene

ENSMUSG00000021245

Gene Name

mutL homolog 3

Synonyms

MMRRC Submission

038777-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0587 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

85281294-85317373 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 85313193 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 998 (V998M)

Ref Sequence

ENSEMBL: ENSMUSP00000152840 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000019378] [ENSMUST00000166821] [ENSMUST00000220854] [ENSMUST00000223230]

AlphaFold

A0A1Y7VMP7

Predicted Effect

probably benign
Transcript: ENSMUST00000019378
AA Change: V998M

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000019378
Gene: ENSMUSG00000021245
AA Change: V998M

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: ENSMUST00000166821
AA Change: V998M

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000129900
Gene: ENSMUSG00000021245
AA Change: V998M

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: ENSMUST00000220854
AA Change: V998M

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

Predicted Effect

probably benign
Transcript: ENSMUST00000223230

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.6%
20x: 95.3%

Validation Efficiency

94% (34/36)

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: 33 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310061I04Rik	T	C	17: 36,203,855 (GRCm39)	*212W	probably null	Het
Abca1	A	G	4: 53,107,035 (GRCm39)	Y231H	probably benign	Het
Abca5	T	G	11: 110,202,203 (GRCm39)	I401L	probably benign	Het
Ak2	A	G	4: 128,896,171 (GRCm39)	D112G	probably damaging	Het
Ankrd60	T	A	2: 173,410,644 (GRCm39)	D292V	possibly damaging	Het
Bank1	A	G	3: 135,919,798 (GRCm39)		probably benign	Het
Bod1l	G	A	5: 41,978,980 (GRCm39)	S778L	probably benign	Het
Cep76	C	A	18: 67,756,245 (GRCm39)	E529*	probably null	Het
Col24a1	T	C	3: 144,998,906 (GRCm39)	V13A	possibly damaging	Het
Ctsc	T	A	7: 87,946,437 (GRCm39)	H154Q	probably benign	Het
Ctsf	A	G	19: 4,905,766 (GRCm39)	E87G	probably benign	Het
Dmxl1	A	T	18: 50,068,374 (GRCm39)	T2716S	probably benign	Het
Espl1	A	G	15: 102,212,382 (GRCm39)		probably benign	Het
Fcsk	T	A	8: 111,609,957 (GRCm39)	Q1019L	probably damaging	Het
Hnrnpul1	T	A	7: 25,444,657 (GRCm39)	Y217F	possibly damaging	Het
Kmt2a	A	T	9: 44,758,831 (GRCm39)	M1039K	probably damaging	Het
Large1	T	C	8: 73,585,961 (GRCm39)	N382D	probably damaging	Het
Madd	A	G	2: 90,977,230 (GRCm39)	V1402A	probably damaging	Het
Myo1c	A	G	11: 75,548,616 (GRCm39)	Y71C	probably damaging	Het
Myt1l	G	A	12: 29,861,634 (GRCm39)	D139N	unknown	Het
Nes	C	A	3: 87,885,876 (GRCm39)	H1378Q	probably benign	Het
Or4c12	T	C	2: 89,773,736 (GRCm39)	H241R	probably damaging	Het
Otud6b	T	C	4: 14,815,661 (GRCm39)	E243G	probably benign	Het
Pak3	TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	X: 142,526,889 (GRCm39)		probably benign	Het
Pcm1	G	T	8: 41,739,088 (GRCm39)	R912L	probably damaging	Het
Piezo2	A	G	18: 63,155,497 (GRCm39)	I2449T	possibly damaging	Het
Slc12a5	G	A	2: 164,818,453 (GRCm39)	M217I	probably damaging	Het
Sorl1	C	A	9: 41,895,802 (GRCm39)	W1784C	probably damaging	Het
Spatc1l	A	G	10: 76,400,011 (GRCm39)	R178G	possibly damaging	Het
Strada	A	C	11: 106,061,790 (GRCm39)	Y154D	probably damaging	Het
Syt6	A	G	3: 103,532,887 (GRCm39)	T424A	probably damaging	Het
Tbx1	C	T	16: 18,402,243 (GRCm39)	A245T	possibly damaging	Het
Tmem143	T	C	7: 45,556,478 (GRCm39)	L161P	probably damaging	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
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
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'- AGCAACGAATGTGCTAAGTCCTGTC -3'
(R):5'- TGAGAAGTCCGCTGCATCACTG -3'

Sequencing Primer
(F):5'- AATGTGCTAAGTCCTGTCATTCTG -3'
(R):5'- ATTCTGCCACAGAGGATGGTC -3'

Posted On

2013-07-11