Mutagenetix > Incidental Mutation

Incidental Mutation 'R7995:Mlh1'

616039

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) question?

Stock #

R7995 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

111057296-111100854 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 111064989 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Lysine at position 555 (N555K)

Ref Sequence

ENSEMBL: ENSMUSP00000035079 (fasta)

Gene Model

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

AlphaFold

Q9JK91

Predicted Effect

probably damaging
Transcript: ENSMUST00000035079
AA Change: N555K

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

SMART Domains

Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: N555K

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700003H04Rik	T	A	3: 124,350,528 (GRCm39)	T137S	unknown	Het
Apbb1	T	C	7: 105,214,852 (GRCm39)	D462G	probably benign	Het
Arhgef1	T	G	7: 24,618,641 (GRCm39)	L387R	probably damaging	Het
Ass1	A	G	2: 31,376,552 (GRCm39)	I139V	probably benign	Het
B4galt5	A	G	2: 167,143,296 (GRCm39)	V376A	probably damaging	Het
Bdkrb1	A	G	12: 105,571,379 (GRCm39)	N315S	probably damaging	Het
Brap	A	T	5: 121,820,909 (GRCm39)	I429L	probably benign	Het
Capn2	A	G	1: 182,306,111 (GRCm39)		probably null	Het
Car10	A	G	11: 93,487,948 (GRCm39)	Y215C	probably damaging	Het
Ccdc102a	T	C	8: 95,634,495 (GRCm39)	T365A	probably damaging	Het
Cdc42ep1	A	G	15: 78,731,696 (GRCm39)	H47R	probably damaging	Het
Celsr3	G	A	9: 108,722,282 (GRCm39)	S2734N	probably damaging	Het
Cers5	A	C	15: 99,638,823 (GRCm39)		probably null	Het
Cfap43	T	C	19: 47,886,462 (GRCm39)	E51G	probably damaging	Het
Cftr	T	A	6: 18,214,155 (GRCm39)	D110E	probably damaging	Het
Cimap2	T	A	4: 106,473,112 (GRCm39)	H57L	probably benign	Het
Cntnap5a	A	G	1: 116,499,277 (GRCm39)	K1176E	probably damaging	Het
Dlx6	A	T	6: 6,867,277 (GRCm39)	R293S	probably damaging	Het
Dnah2	A	T	11: 69,411,563 (GRCm39)	F353Y	possibly damaging	Het
Dnajc13	A	T	9: 104,051,562 (GRCm39)	I1765N	probably damaging	Het
Ercc6	G	T	14: 32,284,526 (GRCm39)	R763L	probably damaging	Het
Furin	T	C	7: 80,045,195 (GRCm39)	N243S	probably damaging	Het
Hace1	A	G	10: 45,465,588 (GRCm39)	E48G	probably damaging	Het
Kcnv1	G	A	15: 44,972,743 (GRCm39)	T380I	probably damaging	Het
Klk4	T	A	7: 43,533,010 (GRCm39)	I32N	probably damaging	Het
Lingo2	T	C	4: 35,709,425 (GRCm39)	E185G	probably damaging	Het
Lrba	T	A	3: 86,526,858 (GRCm39)	W2239R	probably damaging	Het
Mical2	T	A	7: 111,980,975 (GRCm39)	D316E	probably benign	Het
Mroh2b	G	A	15: 4,950,839 (GRCm39)	W579*	probably null	Het
Mycs	G	A	X: 5,380,858 (GRCm39)	P74L	probably damaging	Het
Or5p62	A	T	7: 107,771,207 (GRCm39)	L248H	probably damaging	Het
Or6c1	T	C	10: 129,518,509 (GRCm39)	Y33C	probably damaging	Het
Pak2	T	C	16: 31,846,590 (GRCm39)	I365V	possibly damaging	Het
Pcdhga11	C	A	18: 37,890,078 (GRCm39)	S362*	probably null	Het
Pdk4	C	T	6: 5,487,093 (GRCm39)	V318M	probably benign	Het
Phc2	C	T	4: 128,603,401 (GRCm39)	T177M	probably damaging	Het
Phldb1	A	T	9: 44,626,669 (GRCm39)	L592Q	probably damaging	Het
Pigr	A	G	1: 130,769,423 (GRCm39)	Y78C	probably damaging	Het
Pnkp	T	A	7: 44,507,960 (GRCm39)	Y94*	probably null	Het
Polr2b	T	C	5: 77,473,614 (GRCm39)	V310A	possibly damaging	Het
Pramel21	A	G	4: 143,342,570 (GRCm39)	I226V	possibly damaging	Het
Prl7d1	T	A	13: 27,894,054 (GRCm39)	I171L	probably benign	Het
Rpusd4	A	G	9: 35,184,017 (GRCm39)	Y224C	probably damaging	Het
Scara5	C	A	14: 65,997,057 (GRCm39)	R390S	possibly damaging	Het
Scin	C	T	12: 40,129,804 (GRCm39)	V330I	probably benign	Het
Sdr42e1	T	A	8: 118,390,007 (GRCm39)	R211S	probably benign	Het
Slc36a3	C	A	11: 55,020,495 (GRCm39)	A292S	probably benign	Het
Spata31d1a	T	C	13: 59,848,924 (GRCm39)	D1068G	probably benign	Het
Srd5a1	T	A	13: 69,759,338 (GRCm39)	D10V	probably damaging	Het
Sspo	G	T	6: 48,469,823 (GRCm39)	C4507F	probably damaging	Het
Tmem94	G	A	11: 115,688,797 (GRCm39)	E1335K	probably damaging	Het
Tnfrsf13b	C	T	11: 61,031,742 (GRCm39)	Q28*	probably null	Het
Tspan3	A	T	9: 56,054,438 (GRCm39)	F88I	probably benign	Het
Ttn	T	C	2: 76,592,519 (GRCm39)	K20871R	probably benign	Het
Ube2j2	C	A	4: 156,041,795 (GRCm39)	Y263*	probably null	Het
Vcan	T	C	13: 89,839,977 (GRCm39)	T1856A	probably benign	Het
Vrk3	T	C	7: 44,413,585 (GRCm39)	L218P	probably damaging	Het
Zfp236	G	T	18: 82,657,461 (GRCm39)	H761N	probably damaging	Het
Zfp462	C	A	4: 55,011,907 (GRCm39)	A1291E	probably damaging	Het
Zfp827	T	A	8: 79,844,887 (GRCm39)	S686T	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
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
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'- AGCTAAGAGTTGGGCTTCTCAAG -3'
(R):5'- CAACGTTACTTGTGTGGGACTG -3'

Sequencing Primer
(F):5'- CCATCATGTAAATGGGAAACGGTC -3'
(R):5'- ACTGGAGGTATGAAGAGGTCTTTAC -3'

Posted On

2020-01-23