Mutagenetix > Incidental Mutation

Incidental Mutation 'R5007:Mlh1'

446609

Institutional Source

Beutler Lab

Gene Symbol

Mlh1

Ensembl Gene

ENSMUSG00000032498

Gene Name

mutL homolog 1

Synonyms

1110035C23Rik, colon cancer, nonpolyposis type 2

MMRRC Submission

042598-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5007 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

111057296-111100854 bp(-) (GRCm39)

Type of Mutation

makesense

DNA Base Change (assembly)

A to G at 111100478 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Stop codon to Arginine at position 39 (*39R)

Ref Sequence

ENSEMBL: ENSMUSP00000143786 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000035079] [ENSMUST00000060711] [ENSMUST00000135218] [ENSMUST00000135807]

AlphaFold

Q9JK91

Predicted Effect

possibly damaging
Transcript: ENSMUST00000035079
AA Change: C39R

PolyPhen 2 Score 0.935 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: C39R

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: ENSMUST00000060711

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123869

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000134316

Predicted Effect

probably null
Transcript: ENSMUST00000135218
AA Change: *39R

Predicted Effect

probably benign
Transcript: ENSMUST00000135807

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000200053

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 99.0%
3x: 98.1%
10x: 95.6%
20x: 89.6%

Validation Efficiency

99% (89/90)

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310022A10Rik	C	G	7: 27,278,192 (GRCm39)	T242R	probably damaging	Het
Abca8b	T	C	11: 109,827,590 (GRCm39)	T1473A	probably damaging	Het
Adam22	T	C	5: 8,217,393 (GRCm39)	Y134C	probably damaging	Het
Alg9	T	A	9: 50,699,524 (GRCm39)	M183K	probably damaging	Het
Ambra1	T	C	2: 91,602,655 (GRCm39)	I213T	possibly damaging	Het
Ankrd55	T	A	13: 112,504,466 (GRCm39)	V376D	probably benign	Het
Ano4	A	C	10: 88,948,807 (GRCm39)	V166G	probably benign	Het
Aox3	T	A	1: 58,202,583 (GRCm39)	C730S	probably benign	Het
Apc	T	A	18: 34,446,016 (GRCm39)	Y953N	probably damaging	Het
Ass1	T	C	2: 31,391,544 (GRCm39)	F273S	possibly damaging	Het
Atg2b	T	C	12: 105,610,135 (GRCm39)		probably null	Het
B3gnt9	A	G	8: 105,981,122 (GRCm39)	Y89H	probably damaging	Het
Cd38	T	G	5: 44,063,506 (GRCm39)	F200V	probably damaging	Het
Cep170	G	T	1: 176,597,380 (GRCm39)	R388S	probably benign	Het
Col22a1	A	T	15: 71,816,271 (GRCm39)	D614E	probably damaging	Het
Crybg3	C	A	16: 59,378,463 (GRCm39)		probably benign	Het
Ctdp1	A	T	18: 80,463,695 (GRCm39)	S114T	probably damaging	Het
Dctd	C	T	8: 48,590,449 (GRCm39)		probably benign	Het
Dmtf1	T	C	5: 9,172,439 (GRCm39)		probably benign	Het
Dnhd1	G	A	7: 105,362,283 (GRCm39)	V3715M	probably damaging	Het
Dok1	A	T	6: 83,009,297 (GRCm39)	L185H	probably damaging	Het
Dpep1	T	C	8: 123,926,117 (GRCm39)	V152A	probably damaging	Het
Eif2ak1	G	T	5: 143,810,698 (GRCm39)	R136L	probably benign	Het
Eml5	A	T	12: 98,797,224 (GRCm39)	S1063T	probably damaging	Het
Fam171b	T	A	2: 83,685,853 (GRCm39)	L179*	probably null	Het
Flot1	G	T	17: 36,135,267 (GRCm39)		probably benign	Het
Fmn2	A	T	1: 174,571,866 (GRCm39)	H1491L	probably damaging	Het
Frem1	C	T	4: 82,859,049 (GRCm39)		probably benign	Het
Gdf2	A	G	14: 33,666,863 (GRCm39)	D195G	probably benign	Het
Golga4	T	G	9: 118,387,368 (GRCm39)	C1497G	probably benign	Het
Gpaa1	T	A	15: 76,215,868 (GRCm39)	C33*	probably null	Het
Hectd1	A	T	12: 51,849,443 (GRCm39)	C254S	possibly damaging	Het
Hspa1b	C	T	17: 35,177,086 (GRCm39)	A300T	probably benign	Het
Igf2bp2	A	G	16: 21,898,246 (GRCm39)	I233T	probably damaging	Het
Iqce	C	A	5: 140,661,003 (GRCm39)	A491S	possibly damaging	Het
Irak3	A	G	10: 119,982,334 (GRCm39)		probably null	Het
Kcnip1	T	A	11: 33,592,495 (GRCm39)	H124L	probably benign	Het
Klhdc10	G	A	6: 30,450,640 (GRCm39)	R393Q	probably benign	Het
Klhl28	C	T	12: 65,004,001 (GRCm39)	E171K	probably damaging	Het
Map2	T	C	1: 66,452,448 (GRCm39)	V288A	possibly damaging	Het
Mdp1	C	T	14: 55,896,683 (GRCm39)	R126Q	probably damaging	Het
Meltf	A	G	16: 31,706,380 (GRCm39)	D288G	possibly damaging	Het
Mgat4e	T	A	1: 134,468,890 (GRCm39)	I385F	probably benign	Het
Mical3	A	C	6: 121,015,030 (GRCm39)	V211G	probably damaging	Het
Mre11a	A	G	9: 14,721,116 (GRCm39)	D345G	probably benign	Het
Mroh2a	GCCC	GC	1: 88,159,979 (GRCm39)		probably null	Het
Msh2	C	A	17: 88,030,841 (GRCm39)	A906E	probably benign	Het
Nat1	T	G	8: 67,944,077 (GRCm39)	L154R	probably benign	Het
Nlrp4a	A	G	7: 26,161,905 (GRCm39)	D851G	probably damaging	Het
Npas4	A	C	19: 5,039,684 (GRCm39)	V54G	possibly damaging	Het
Or13n4	T	C	7: 106,423,364 (GRCm39)	Y123C	probably damaging	Het
Pcbp4	G	A	9: 106,339,292 (GRCm39)	G100R	probably damaging	Het
Pcdh17	A	G	14: 84,770,737 (GRCm39)	T1072A	probably benign	Het
Pcdh18	T	C	3: 49,708,906 (GRCm39)	N803S	probably benign	Het
Ppat	C	T	5: 77,076,525 (GRCm39)		probably benign	Het
Ppm1l	T	A	3: 69,224,931 (GRCm39)	L11Q	probably damaging	Het
Pram1	T	A	17: 33,864,411 (GRCm39)	V658E	probably damaging	Het
Prr12	C	T	7: 44,699,225 (GRCm39)		probably benign	Het
Prxl2b	A	G	4: 154,981,531 (GRCm39)		probably null	Het
Ptprq	A	G	10: 107,444,137 (GRCm39)	V1489A	probably benign	Het
Ryr1	T	A	7: 28,768,540 (GRCm39)	I2817F	probably damaging	Het
Sall2	A	G	14: 52,551,950 (GRCm39)	L413P	probably damaging	Het
Slc7a9	T	A	7: 35,153,554 (GRCm39)	M185K	probably benign	Het
Stag2	C	T	X: 41,355,130 (GRCm39)	H1149Y	possibly damaging	Het
Timm10b	T	A	7: 105,290,298 (GRCm39)	Y64N	probably damaging	Het
Tmem30c	T	C	16: 57,086,868 (GRCm39)	T312A	probably benign	Het
Tmem9b	G	T	7: 109,344,550 (GRCm39)	C17*	probably null	Het
Vmn2r68	C	A	7: 84,881,622 (GRCm39)	R486L	probably benign	Het
Xkr9	T	A	1: 13,771,387 (GRCm39)	I301N	probably damaging	Het
Xpo7	T	C	14: 70,925,704 (GRCm39)	Q446R	probably damaging	Het
Ythdf3	T	C	3: 16,259,362 (GRCm39)	V503A	possibly damaging	Het
Zfp280b	T	A	10: 75,875,048 (GRCm39)	V309D	probably damaging	Het
Zfp53	T	A	17: 21,729,772 (GRCm39)	C602S	probably benign	Het
Zfp616	A	T	11: 73,974,643 (GRCm39)	N395I	possibly damaging	Het
Zfp644	T	C	5: 106,783,867 (GRCm39)	I862M	probably benign	Het
Zfp715	T	C	7: 42,949,019 (GRCm39)	T314A	possibly damaging	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
PIT4495001:Mlh1	UTSW	9	111,076,328 (GRCm39)	missense	probably benign	0.00
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
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'- TTCGGCCGTGTGCATAATG -3'
(R):5'- TAAAAGCGCTTGACTGGCATTC -3'

Sequencing Primer
(F):5'- GCCGTGTGCATAATGGGAAACC -3'
(R):5'- CATTCATGCTGCCCAATCAG -3'

Posted On

2016-11-22