Mutagenetix > Incidental Mutation

Incidental Mutation 'R8804:Mlh1'

671928

Institutional Source

Beutler Lab

Gene Symbol

Mlh1

Ensembl Gene

ENSMUSG00000032498

Gene Name

mutL homolog 1

Synonyms

1110035C23Rik, colon cancer, nonpolyposis type 2

MMRRC Submission

068641-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R8804 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

111057296-111100854 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 111093972 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 90 (D90G)

Ref Sequence

ENSEMBL: ENSMUSP00000035079 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000035079] [ENSMUST00000135218] [ENSMUST00000135695]

AlphaFold

Q9JK91

Predicted Effect

probably damaging
Transcript: ENSMUST00000035079
AA Change: D90G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: D90G

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.2%

Validation Efficiency

98% (79/81)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700064H15Rik	T	C	3: 19,682,820 (GRCm39)		probably benign	Het
Adamts1	A	G	16: 85,599,300 (GRCm39)	F100S	probably damaging	Het
Adamts5	A	G	16: 85,666,800 (GRCm39)		probably benign	Het
Adgrb2	T	A	4: 129,899,212 (GRCm39)	W309R	probably damaging	Het
Adgrl2	A	T	3: 148,552,652 (GRCm39)	V617E	probably damaging	Het
Akt1	T	C	12: 112,625,041 (GRCm39)	E169G	probably damaging	Het
Arhgap40	A	G	2: 158,389,626 (GRCm39)	T600A	probably benign	Het
B4galt3	C	T	1: 171,103,947 (GRCm39)	H395Y	probably benign	Het
BC024139	T	G	15: 76,008,284 (GRCm39)	T376P	possibly damaging	Het
Bin3	A	G	14: 70,361,296 (GRCm39)	R22G	probably damaging	Het
Cadps2	A	T	6: 23,496,805 (GRCm39)	I480N	probably damaging	Het
Camsap3	A	G	8: 3,652,624 (GRCm39)	T401A	probably benign	Het
Ccdc168	T	C	1: 44,095,809 (GRCm39)	N1763S	probably benign	Het
Cdhr5	T	C	7: 140,849,320 (GRCm39)	T747A	probably benign	Het
Chn2	A	G	6: 54,250,061 (GRCm39)	I193V	probably benign	Het
Clca3b	T	C	3: 144,544,898 (GRCm39)	N363S	probably benign	Het
Clec7a	T	C	6: 129,442,518 (GRCm39)	T125A	probably benign	Het
Cys1	A	T	12: 24,718,610 (GRCm39)	L81Q	unknown	Het
Dcbld2	G	A	16: 58,281,412 (GRCm39)		probably benign	Het
Ddx60	T	A	8: 62,411,640 (GRCm39)	D497E	probably benign	Het
Dnah2	T	C	11: 69,356,511 (GRCm39)	I2117V	probably benign	Het
Dnah6	G	A	6: 73,042,756 (GRCm39)	S3274F	probably benign	Het
Dock9	A	T	14: 121,842,595 (GRCm39)	I1225N	probably damaging	Het
Egfr	A	G	11: 16,819,339 (GRCm39)	T290A	probably benign	Het
Elmod2	T	A	8: 84,046,150 (GRCm39)	K142N	probably benign	Het
Ephx2	T	C	14: 66,324,469 (GRCm39)	T441A	probably benign	Het
Fam234a	A	G	17: 26,435,531 (GRCm39)		probably benign	Het
Fer1l4	C	A	2: 155,893,914 (GRCm39)	E102D	probably benign	Het
Fermt3	A	G	19: 6,991,694 (GRCm39)		probably benign	Het
Fgd5	C	T	6: 91,964,507 (GRCm39)	R247C	probably benign	Het
Gm14443	G	A	2: 175,011,652 (GRCm39)	H265Y	probably damaging	Het
Gykl1	A	G	18: 52,827,608 (GRCm39)	D272G	probably benign	Het
Hip1r	T	C	5: 124,139,575 (GRCm39)	S952P	possibly damaging	Het
Hmcn2	A	G	2: 31,315,393 (GRCm39)	N3714S	probably benign	Het
Ighv1-36	G	T	12: 114,843,581 (GRCm39)	T93K	probably benign	Het
Igsf10	T	G	3: 59,243,876 (GRCm39)	T153P	probably damaging	Het
Kif13b	T	C	14: 64,987,791 (GRCm39)	C773R	probably damaging	Het
Lipf	T	A	19: 33,942,198 (GRCm39)	Y43N	probably damaging	Het
Msh5	A	T	17: 35,251,830 (GRCm39)	I410K	probably benign	Het
Mylk3	T	C	8: 86,085,874 (GRCm39)	D220G	probably benign	Het
Ncdn	G	A	4: 126,643,898 (GRCm39)	A308V	probably benign	Het
Nfu1	T	A	6: 86,993,414 (GRCm39)		probably benign	Het
Nup153	A	G	13: 46,840,635 (GRCm39)	V991A	probably benign	Het
Nup188	T	A	2: 30,220,891 (GRCm39)	H960Q	probably benign	Het
Parp4	G	T	14: 56,853,900 (GRCm39)	E839*	probably null	Het
Pfas	T	C	11: 68,881,908 (GRCm39)	N30D		Het
Pitpnc1	T	A	11: 107,103,431 (GRCm39)	N223Y	probably damaging	Het
Plaat1	T	A	16: 29,039,205 (GRCm39)	V95E	probably benign	Het
Plod1	C	T	4: 147,997,778 (GRCm39)	V644I	probably damaging	Het
Pou2f1	T	C	1: 165,708,039 (GRCm39)	T548A	unknown	Het
Psg20	A	T	7: 18,416,584 (GRCm39)	N177K	possibly damaging	Het
Psmb8	T	A	17: 34,419,225 (GRCm39)	I173N	probably damaging	Het
Rimkla	G	A	4: 119,325,273 (GRCm39)	Q379*	probably null	Het
Rnasel	G	T	1: 153,629,661 (GRCm39)	G59V	probably damaging	Het
Rptn	A	T	3: 93,303,150 (GRCm39)	D161V	probably damaging	Het
Scrt1	C	A	15: 76,403,411 (GRCm39)	C193F	unknown	Het
Sdk2	G	T	11: 113,763,978 (GRCm39)	Y269*	probably null	Het
Sfxn2	G	C	19: 46,574,243 (GRCm39)		probably benign	Het
Slc17a4	G	T	13: 24,087,245 (GRCm39)	T264K	probably benign	Het
Slfn8	T	A	11: 82,907,639 (GRCm39)	Q301H	possibly damaging	Het
Sntb1	G	A	15: 55,655,523 (GRCm39)	S231F	probably benign	Het
Spag17	T	A	3: 99,874,506 (GRCm39)	S137T	probably benign	Het
Srd5a2	A	T	17: 74,354,629 (GRCm39)	V65E	possibly damaging	Het
Stk11ip	A	G	1: 75,511,900 (GRCm39)	H967R	probably benign	Het
Sun1	A	G	5: 139,216,920 (GRCm39)	T320A	probably benign	Het
Svep1	A	G	4: 58,206,043 (GRCm39)	S112P	possibly damaging	Het
Tacc2	T	C	7: 130,294,693 (GRCm39)	L15P	probably benign	Het
Tas2r140	T	A	6: 133,032,326 (GRCm39)	N144I	probably damaging	Het
Thpo	T	A	16: 20,544,707 (GRCm39)	R174S	probably damaging	Het
Tnik	A	T	3: 28,648,202 (GRCm39)	Q418L	unknown	Het
Tnr	A	T	1: 159,685,882 (GRCm39)	Q371L	probably benign	Het
Tulp2	G	A	7: 45,170,398 (GRCm39)	R439Q	probably damaging	Het
Uchl4	G	T	9: 64,142,606 (GRCm39)	W29L	probably damaging	Het
Vrk3	T	A	7: 44,407,270 (GRCm39)	C80*	probably null	Het
Washc4	T	C	10: 83,408,015 (GRCm39)	L540P	probably damaging	Het
Wscd1	T	C	11: 71,675,161 (GRCm39)	F356S	probably damaging	Het
Wwc1	A	T	11: 35,774,144 (GRCm39)	M372K	probably benign	Het
Zfhx2	A	G	14: 55,312,191 (GRCm39)	F168L	probably benign	Het
Zfp28	A	G	7: 6,393,399 (GRCm39)	D175G	probably 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
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
R9562:Mlh1	UTSW	9	111,060,013 (GRCm39)	missense

Predicted Primers

PCR Primer
(F):5'- GAATTTCTCAGTCACGGAAAGC -3'
(R):5'- CCCAGTAAAGTGAAAATCTAGGTCG -3'

Sequencing Primer
(F):5'- CTCAGTCACGGAAAGCTAAATTTG -3'
(R):5'- GGAAGTTGGTACTAATTTAGACCTCC -3'

Posted On

2021-04-30