Mutagenetix > Incidental Mutations

Incidental Mutation 'R7348:Mlh3'

570376

Institutional Source

Beutler Lab

Gene Symbol

Mlh3

Ensembl Gene

ENSMUSG00000021245

Gene Name

mutL homolog 3

Synonyms

MMRRC Submission

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7348 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

85234520-85270599 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 85267441 bp

Zygosity

Heterozygous

Amino Acid Change

Proline to Glutamine at position 657 (P657Q)

Ref Sequence

ENSEMBL: ENSMUSP00000019378 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000008966] [ENSMUST00000019378] [ENSMUST00000117138] [ENSMUST00000166821] [ENSMUST00000220854] [ENSMUST00000223230]

Predicted Effect

probably benign
Transcript: ENSMUST00000008966

SMART Domains

Protein: ENSMUSP00000008966
Gene: ENSMUSG00000008822

Domain	Start	End	E-Value	Type
Pfam:Acylphosphatase	1	98	6e-26	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000019378
AA Change: P657Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000019378
Gene: ENSMUSG00000021245
AA Change: P657Q

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: ENSMUST00000117138

SMART Domains

Protein: ENSMUSP00000113161
Gene: ENSMUSG00000008822

Domain	Start	End	E-Value	Type
Pfam:Acylphosphatase	1	98	6e-26	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000166821
AA Change: P657Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000129900
Gene: ENSMUSG00000021245
AA Change: P657Q

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 damaging
Transcript: ENSMUST00000220854
AA Change: P657Q

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

Predicted Effect

probably benign
Transcript: ENSMUST00000223230

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.8%

Validation Efficiency

99% (80/81)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abra	G	A	15: 41,866,159	R282C	probably damaging	Het
Adcy2	T	A	13: 68,734,675	E314D	possibly damaging	Het
Adgrl2	A	T	3: 148,817,766	I274N		Het
Adpgk	A	G	9: 59,313,786	I292V	probably benign	Het
Agtrap	G	T	4: 148,080,597	F124L	probably benign	Het
Ankrd26	A	G	6: 118,508,564	Y1450H	probably damaging	Het
Ap4e1	A	T	2: 127,061,976	S933C	probably damaging	Het
Ap4e1	G	T	2: 127,061,977	S933I	possibly damaging	Het
Ap5s1	A	T	2: 131,212,652	T128S	possibly damaging	Het
Arih1	T	C	9: 59,486,058	Y97C	probably damaging	Het
Atp1a3	A	G	7: 24,978,826	F1034S	unknown	Het
Bmp6	T	C	13: 38,485,903	S388P	probably benign	Het
Ccdc39	A	G	3: 33,832,676	V261A	possibly damaging	Het
Ccdc66	C	T	14: 27,500,336	C150Y	probably damaging	Het
Cep89	G	A	7: 35,429,928	R630H	probably damaging	Het
Cln6	A	G	9: 62,849,176	S201G	probably benign	Het
Cntnap4	T	C	8: 112,665,277	Y125H	probably damaging	Het
Copa	A	G	1: 172,102,223	T286A	possibly damaging	Het
Cul9	A	T	17: 46,510,993	I1852K	possibly damaging	Het
Cyp2j8	C	A	4: 96,444,640	A490S	probably benign	Het
Cyp2t4	A	G	7: 27,157,251	I239V	probably benign	Het
E2f7	C	T	10: 110,780,975	T692I	probably damaging	Het
Fastkd5	A	G	2: 130,615,135	Y512H	probably damaging	Het
Fastkd5	A	C	2: 130,616,439	M77R	probably benign	Het
Fhod3	A	G	18: 25,090,467	R957G	possibly damaging	Het
Gm17018	A	G	19: 45,572,466	Y111C	probably damaging	Het
H6pd	C	A	4: 149,983,902		probably null	Het
Haus5	G	T	7: 30,656,966	P544Q	possibly damaging	Het
Ifi207	CTGTTGATGAAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATACAGTTGCTTGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATAGAGTTGCATATGGAGCCAGGAGGATGCTATATGTTGTTGATGAAGTTGCATGTGGAGCCAGGAG	CTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATACAGTTGCTTGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATAGAGTTGCATATGGAGCCAGGAGGATGCTATATGTTGTTGATGAAGTTGCATGTGGAGCCAGGAG	1: 173,729,196		probably benign	Het
Igf2r	A	G	17: 12,703,484	Y1248H	probably damaging	Het
Izumo3	T	C	4: 92,147,218	N6S	possibly damaging	Het
Lrp6	G	T	6: 134,450,818	P1604T	probably damaging	Het
Map3k8	T	A	18: 4,340,561	H251L	probably damaging	Het
Mapre3	T	C	5: 30,861,829	Y6H	probably benign	Het
Mrgpra1	T	C	7: 47,335,409	Y174C	probably benign	Het
Ms4a6d	G	A	19: 11,590,073	Q155*	probably null	Het
Myh1	C	A	11: 67,202,539	P152Q	probably damaging	Het
Myh6	A	T	14: 54,952,259	L1110Q	probably damaging	Het
Nf1	T	A	11: 79,536,850	S1778T	probably benign	Het
Nkpd1	G	A	7: 19,524,416	E707K	probably damaging	Het
Nlrp4a	A	G	7: 26,444,273	E21G	probably damaging	Het
Nr4a3	T	G	4: 48,051,290	S15A	possibly damaging	Het
Olfr1354	A	G	10: 78,917,562	T241A	probably damaging	Het
Olfr453	T	C	6: 42,744,856	L273S	possibly damaging	Het
Olfr488	T	C	7: 108,256,123	D5G	probably benign	Het
Olfr491	T	C	7: 108,317,713	V273A	possibly damaging	Het
Parg	G	A	14: 32,250,079	R677Q	possibly damaging	Het
Pcsk5	A	T	19: 17,456,818	C1395*	probably null	Het
Psd2	G	A	18: 35,980,336	S287N	possibly damaging	Het
Psd3	T	C	8: 67,790,931	N685S	possibly damaging	Het
Pygb	C	T	2: 150,786,983	T39M	probably benign	Het
Rbfox1	C	A	16: 7,408,024	Y351*	probably null	Het
Rftn1	A	G	17: 50,004,323	L396P	probably damaging	Het
S1pr1	A	G	3: 115,712,061	Y295H	probably damaging	Het
Scn5a	T	C	9: 119,535,833	M440V	probably benign	Het
Sel1l2	T	C	2: 140,265,724	N240S	probably benign	Het
Skint1	T	C	4: 112,021,573	L234P	probably damaging	Het
Skint11	T	A	4: 114,244,722	Y311N	probably benign	Het
Slc6a5	A	T	7: 49,910,167		probably benign	Het
Tas2r134	T	C	2: 51,628,402	S298P	possibly damaging	Het
Tbcd	C	A	11: 121,594,311	A773D	probably benign	Het
Tgoln1	G	C	6: 72,616,278	T73R	probably benign	Het
Tmem184a	T	C	5: 139,814,054	E24G	probably null	Het
Tmem207	C	A	16: 26,516,827	W53C	possibly damaging	Het
Tns1	T	A	1: 73,916,917	H549L	possibly damaging	Het
Ttc37	T	C	13: 76,182,884	F1478L	possibly damaging	Het
Ttc41	G	T	10: 86,750,348	E839*	probably null	Het
Ufd1	T	G	16: 18,815,885		probably benign	Het
Usp28	A	G	9: 49,030,877	E713G	probably benign	Het
Utrn	A	G	10: 12,748,018	W159R	probably damaging	Het
Vcl	C	T	14: 21,003,150	A411V	probably benign	Het
Vcl	T	A	14: 21,008,952	C545*	probably null	Het
Vmn1r120	A	T	7: 21,053,452	S111R	probably damaging	Het
Wwox	T	A	8: 114,472,652	C146S	probably benign	Het
Zbtb2	T	C	10: 4,374,574	T57A	possibly damaging	Het
Zfp362	T	C	4: 128,777,217	D336G	possibly damaging	Het
Zfp628	G	A	7: 4,921,818	G1013E	probably damaging	Het
Zfp704	A	G	3: 9,474,598	S231P	probably damaging	Het
Zhx3	G	T	2: 160,782,118	S43*	probably null	Het

Other mutations in Mlh3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01402:Mlh3	APN	12	85267929	missense	probably benign
IGL01462:Mlh3	APN	12	85266736	missense	probably benign
IGL01961:Mlh3	APN	12	85266344	missense	probably benign	0.00
IGL02596:Mlh3	APN	12	85240958	critical splice donor site	probably null
IGL03008:Mlh3	APN	12	85240851	missense	probably benign	0.23
IGL03142:Mlh3	APN	12	85250301	critical splice donor site	probably null
R0032:Mlh3	UTSW	12	85245749	intron	probably benign
R0032:Mlh3	UTSW	12	85245749	intron	probably benign
R0078:Mlh3	UTSW	12	85268818	missense	probably damaging	0.98
R0129:Mlh3	UTSW	12	85266140	splice site	probably benign
R0269:Mlh3	UTSW	12	85268405	missense	probably benign	0.00
R0393:Mlh3	UTSW	12	85267587	nonsense	probably null
R0403:Mlh3	UTSW	12	85268968	missense	possibly damaging	0.93
R0409:Mlh3	UTSW	12	85240854	missense	possibly damaging	0.95
R0587:Mlh3	UTSW	12	85266419	missense	probably benign	0.00
R0701:Mlh3	UTSW	12	85267903	missense	probably benign	0.00
R0718:Mlh3	UTSW	12	85247697	missense	possibly damaging	0.86
R0883:Mlh3	UTSW	12	85235714	missense	possibly damaging	0.89
R0989:Mlh3	UTSW	12	85269395	missense	probably benign	0.22
R0990:Mlh3	UTSW	12	85267765	missense	probably benign
R1467:Mlh3	UTSW	12	85237600	nonsense	probably null
R1467:Mlh3	UTSW	12	85237600	nonsense	probably null
R1562:Mlh3	UTSW	12	85266920	missense	probably benign	0.14
R1599:Mlh3	UTSW	12	85268369	missense	probably damaging	1.00
R1694:Mlh3	UTSW	12	85267141	missense	probably damaging	1.00
R1777:Mlh3	UTSW	12	85268754	missense	possibly damaging	0.75
R1822:Mlh3	UTSW	12	85266145	splice site	probably benign
R1874:Mlh3	UTSW	12	85237513	critical splice donor site	probably null
R1914:Mlh3	UTSW	12	85261668	missense	probably benign	0.08
R1915:Mlh3	UTSW	12	85261668	missense	probably benign	0.08
R2075:Mlh3	UTSW	12	85269141	nonsense	probably null
R2083:Mlh3	UTSW	12	85269041	missense	probably benign	0.16
R2267:Mlh3	UTSW	12	85260811	missense	possibly damaging	0.55
R2334:Mlh3	UTSW	12	85268077	missense	probably benign	0.00
R2882:Mlh3	UTSW	12	85267566	missense	probably damaging	1.00
R3623:Mlh3	UTSW	12	85268395	missense	probably damaging	1.00
R3624:Mlh3	UTSW	12	85268395	missense	probably damaging	1.00
R3963:Mlh3	UTSW	12	85268680	missense	possibly damaging	0.94
R4376:Mlh3	UTSW	12	85259198	missense	probably benign	0.00
R5334:Mlh3	UTSW	12	85245761	critical splice donor site	probably null
R5526:Mlh3	UTSW	12	85269373	nonsense	probably null
R5556:Mlh3	UTSW	12	85268493	nonsense	probably null
R5611:Mlh3	UTSW	12	85267445	missense	probably benign	0.21
R5911:Mlh3	UTSW	12	85268455	missense	probably damaging	1.00
R6050:Mlh3	UTSW	12	85240846	missense	possibly damaging	0.89
R6221:Mlh3	UTSW	12	85268418	missense	possibly damaging	0.94
R6377:Mlh3	UTSW	12	85268497	missense	probably damaging	0.97
R6820:Mlh3	UTSW	12	85247723	missense	probably damaging	1.00
R6826:Mlh3	UTSW	12	85245824	missense	probably benign	0.38
R6992:Mlh3	UTSW	12	85235720	missense	probably damaging	1.00
R7217:Mlh3	UTSW	12	85266707	missense	probably benign
R7228:Mlh3	UTSW	12	85235656	missense	probably benign	0.07
R7599:Mlh3	UTSW	12	85268199	nonsense	probably null
R7722:Mlh3	UTSW	12	85267492	missense	probably benign	0.01
R7762:Mlh3	UTSW	12	85268284	missense	possibly damaging	0.63
R7786:Mlh3	UTSW	12	85266737	missense	probably benign	0.00
RF014:Mlh3	UTSW	12	85268029	missense	probably benign
X0024:Mlh3	UTSW	12	85247669	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TCTACACCATGGGAAGGAGG -3'
(R):5'- AAAGGAGCCCAGTAGTCGTG -3'

Sequencing Primer
(F):5'- CCATGGGAAGGAGGATGCATC -3'
(R):5'- CCCAGTAGTCGTGGAAGAGTAAATG -3'

Posted On

2019-09-13