Mutagenetix > Incidental Mutation

Incidental Mutation 'R7607:Mlh1'

588383

Institutional Source

Beutler Lab

Gene Symbol

Mlh1

Ensembl Gene

ENSMUSG00000032498

Gene Name

mutL homolog 1

Synonyms

colon cancer, nonpolyposis type 2, 1110035C23Rik

MMRRC Submission

045677-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7607 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

111228228-111271791 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 111229890 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 689 (S689P)

Ref Sequence

ENSEMBL: ENSMUSP00000035079 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000035078] [ENSMUST00000035079] [ENSMUST00000098340] [ENSMUST00000135218]

AlphaFold

Q9JK91

Predicted Effect

probably benign
Transcript: ENSMUST00000035078

SMART Domains

Protein: ENSMUSP00000035078
Gene: ENSMUSG00000032497

Domain	Start	End	E-Value	Type
Pfam:DUF2051	31	340	2.5e-106	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000035079
AA Change: S689P

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000035079
Gene: ENSMUSG00000032498
AA Change: S689P

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: ENSMUST00000098340

SMART Domains

Protein: ENSMUSP00000095944
Gene: ENSMUSG00000032497

Domain	Start	End	E-Value	Type
Pfam:DUF2051	31	326	2.7e-122	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000135218

Coding Region Coverage

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

Validation Efficiency

99% (69/70)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610010K14Rik	A	T	11: 70,237,557	H30Q	probably damaging	Het
1700012P22Rik	T	A	4: 144,419,762	H107L	probably damaging	Het
A930009A15Rik	G	A	10: 115,581,989		probably null	Het
Abca7	T	C	10: 80,011,833	L1779P	probably damaging	Het
Aff1	G	A	5: 103,849,459	V1140I	possibly damaging	Het
Ano2	C	T	6: 125,712,419	A169V	probably damaging	Het
Atat1	T	C	17: 35,909,107	Y101C	possibly damaging	Het
Atp6v1c1	T	C	15: 38,683,011		probably null	Het
Atp7b	T	G	8: 22,011,506	K912T	probably damaging	Het
Ceacam14	T	C	7: 17,814,321	V112A	possibly damaging	Het
Cobll1	T	C	2: 65,095,857	N1119S	probably benign	Het
Csmd1	G	T	8: 15,918,331	Q3099K	possibly damaging	Het
Cyp3a25	A	G	5: 145,984,981	V381A	possibly damaging	Het
Dctn1	C	T	6: 83,195,069	R948*	probably null	Het
Dhrs3	A	G	4: 144,923,940	T219A	probably benign	Het
Epha7	C	T	4: 28,871,937	S422L	probably benign	Het
Esrp1	A	G	4: 11,384,449	V78A	probably damaging	Het
Evc2	A	G	5: 37,386,856	T650A	possibly damaging	Het
Exoc6b	T	A	6: 84,989,409	K194N	possibly damaging	Het
Fer1l6	G	A	15: 58,662,732	W1809*	probably null	Het
Frmd4a	T	A	2: 4,591,936	L156*	probably null	Het
Gk5	A	T	9: 96,153,210		probably null	Het
Gm3573	A	G	14: 42,189,750	F8L	probably benign	Het
Gm906	T	C	13: 50,250,260	E2G	possibly damaging	Het
Gm9767	G	A	10: 26,078,940	C130Y	unknown	Het
Grip2	T	C	6: 91,788,412	T30A	probably benign	Het
Gskip	C	A	12: 105,698,897	A65E	possibly damaging	Het
Gtf2e2	A	G	8: 33,776,465	R259G	probably benign	Het
Gucy1b2	T	A	14: 62,419,177	I244F	probably damaging	Het
Gxylt2	G	T	6: 100,798,190	V357L	possibly damaging	Het
Hivep3	CGG	CG	4: 120,097,911	1141	probably null	Het
Igdcc4	C	T	9: 65,133,758	P1024S	possibly damaging	Het
Ino80	A	T	2: 119,382,269		probably null	Het
Knl1	T	C	2: 119,095,133	F1881S	possibly damaging	Het
Mbd6	T	C	10: 127,285,230	E518G	unknown	Het
Mmrn2	T	C	14: 34,398,940	I589T	possibly damaging	Het
Mtmr12	C	T	15: 12,257,708	Q291*	probably null	Het
Mup8	T	A	4: 60,222,035	I33F	probably benign	Het
Mylk	C	T	16: 34,894,814	P504L	probably benign	Het
Ntrk3	C	T	7: 78,250,873	A573T	probably benign	Het
Obscn	G	T	11: 58,998,265	S7560R	unknown	Het
Olfr24	A	G	9: 18,754,882	F251S	possibly damaging	Het
Olfr617	A	C	7: 103,584,930	T303P	probably damaging	Het
Pde1c	T	C	6: 56,150,628	T391A	probably damaging	Het
Pla2g4d	T	A	2: 120,288,976	H19L	probably benign	Het
Plce1	C	A	19: 38,524,752	A165E	probably benign	Het
Polr1a	T	C	6: 71,913,021	S75P	probably benign	Het
Psg21	T	C	7: 18,654,783	E128G	probably benign	Het
Radil	A	T	5: 142,494,795	M635K	probably damaging	Het
Radil	A	G	5: 142,506,613	I420T	probably damaging	Het
Rnase11	G	A	14: 51,049,572	T175I	probably damaging	Het
Robo1	C	T	16: 72,563,738	P13S		Het
Slc18a2	C	A	19: 59,284,358	A364D	probably benign	Het
Snph	C	T	2: 151,594,586	D141N	probably damaging	Het
Snrnp70	T	C	7: 45,392,264	K70R	possibly damaging	Het
Snx33	T	C	9: 56,926,713	D24G	probably benign	Het
Spag6	T	A	2: 18,731,962	D165E	possibly damaging	Het
Spata31	T	G	13: 64,921,592	L518R	probably damaging	Het
Sspo	G	A	6: 48,489,727	V4059M	probably damaging	Het
St6galnac2	T	C	11: 116,679,979	Y261C	probably damaging	Het
Stoml1	A	G	9: 58,256,658	R87G	probably damaging	Het
Suv39h2	T	C	2: 3,474,829	T40A	unknown	Het
Terb2	G	T	2: 122,186,475	G26W	probably damaging	Het
Tmem62	T	C	2: 120,996,440	I406T	probably benign	Het
Tnfrsf11a	G	A	1: 105,844,732	V582I	probably benign	Het
Tpsg1	G	T	17: 25,373,210	G86V	probably damaging	Het
Unc13c	T	C	9: 73,669,535	D1480G	probably damaging	Het
Urb1	CACTTAC	CAC	16: 90,772,573		probably benign	Het
Vmn1r48	C	A	6: 90,035,980	V288L	probably benign	Het
Vmn2r13	A	G	5: 109,173,640	V397A	probably damaging	Het
Vmn2r98	A	G	17: 19,067,308	N468D	possibly damaging	Het
Zfhx2	G	T	14: 55,066,231	T1432K	possibly damaging	Het
Zswim5	T	A	4: 116,986,742	D992E	possibly damaging	Het

Other mutations in Mlh1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01306:Mlh1	APN	9	111252912	missense	possibly damaging	0.84
IGL02530:Mlh1	APN	9	111229875	missense	probably benign	0.09
IGL02811:Mlh1	APN	9	111271514	missense	probably benign	0.04
IGL02892:Mlh1	APN	9	111252969	missense	probably benign	0.00
IGL03394:Mlh1	APN	9	111268243	missense	probably damaging	1.00
andalusia	UTSW	9	111271410	makesense	probably null
andalusia2	UTSW	9	111271523	start codon destroyed	probably null	0.93
andalusia3	UTSW	9	111229838	critical splice donor site	probably null
ANU23:Mlh1	UTSW	9	111252912	missense	possibly damaging	0.84
PIT4495001:Mlh1	UTSW	9	111247260	missense	probably benign	0.00
R0496:Mlh1	UTSW	9	111241556	missense	probably benign
R0723:Mlh1	UTSW	9	111271472	missense	probably damaging	1.00
R1395:Mlh1	UTSW	9	111247377	missense	probably damaging	1.00
R1694:Mlh1	UTSW	9	111228475	missense	probably damaging	1.00
R1762:Mlh1	UTSW	9	111229929	missense	probably damaging	1.00
R1865:Mlh1	UTSW	9	111257024	intron	probably benign
R1885:Mlh1	UTSW	9	111258556	missense	probably benign	0.18
R1992:Mlh1	UTSW	9	111228563	missense	probably damaging	0.96
R2186:Mlh1	UTSW	9	111258566	unclassified	probably benign
R2680:Mlh1	UTSW	9	111236017	critical splice acceptor site	probably null
R4693:Mlh1	UTSW	9	111255658	missense	probably damaging	1.00
R4784:Mlh1	UTSW	9	111239798	missense	probably benign
R5007:Mlh1	UTSW	9	111271410	makesense	probably null
R5130:Mlh1	UTSW	9	111229838	critical splice donor site	probably null
R5166:Mlh1	UTSW	9	111241513	missense	probably benign	0.04
R5265:Mlh1	UTSW	9	111271523	start codon destroyed	probably null	0.93
R5481:Mlh1	UTSW	9	111229837	splice site	probably null
R5483:Mlh1	UTSW	9	111231058	missense	possibly damaging	0.82
R5602:Mlh1	UTSW	9	111252878	missense	probably damaging	0.97
R5658:Mlh1	UTSW	9	111247380	missense	probably damaging	0.99
R5890:Mlh1	UTSW	9	111228495	missense	possibly damaging	0.88
R6810:Mlh1	UTSW	9	111241558	missense	possibly damaging	0.52
R7753:Mlh1	UTSW	9	111252863	critical splice donor site	probably null
R7894:Mlh1	UTSW	9	111230077	splice site	probably null
R7912:Mlh1	UTSW	9	111261513	missense	possibly damaging	0.69
R7995:Mlh1	UTSW	9	111235921	missense	probably damaging	1.00
R8097:Mlh1	UTSW	9	111256092	critical splice donor site	probably null
R8280:Mlh1	UTSW	9	111249218	critical splice donor site	probably null
R8804:Mlh1	UTSW	9	111264904	missense	probably damaging	1.00
R9562:Mlh1	UTSW	9	111230945	missense

Predicted Primers

PCR Primer
(F):5'- TGGAAGTCTATGTTCTAGTCCAGC -3'
(R):5'- GAAAAGCCACGTCCCTTCTG -3'

Sequencing Primer
(F):5'- CGCTATAATCTCAGCACTTAGGAGG -3'
(R):5'- TGAACTGTCAAGTCTGTGACC -3'

Posted On

2019-10-24