Mutagenetix > Incidental Mutation

Incidental Mutation 'R4757:Msh4'

358217

Institutional Source

Beutler Lab

Gene Symbol

Msh4

Ensembl Gene

ENSMUSG00000005493

Gene Name

mutS homolog 4

Synonyms

mMsh4, 4930485C04Rik

MMRRC Submission

041973-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.477) question?

Stock #

R4757 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

153857149-153906138 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 153879387 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 360 (H360L)

Ref Sequence

ENSEMBL: ENSMUSP00000140190 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005630] [ENSMUST00000188338] [ENSMUST00000190449]

AlphaFold

Q99MT2

Predicted Effect

possibly damaging
Transcript: ENSMUST00000005630
AA Change: H448L

PolyPhen 2 Score 0.956 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000005630
Gene: ENSMUSG00000005493
AA Change: H448L

Domain	Start	End	E-Value	Type
low complexity region	91	107	N/A	INTRINSIC
Pfam:MutS_II	177	321	2.3e-20	PFAM
MUTSd	352	679	3.77e-37	SMART
MUTSac	695	888	1.6e-81	SMART
Blast:MUTSac	912	956	1e-9	BLAST

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000186220

Predicted Effect

probably damaging
Transcript: ENSMUST00000188338
AA Change: H360L

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000140190
Gene: ENSMUSG00000005493
AA Change: H360L

Domain	Start	End	E-Value	Type
Pfam:MutS_II	89	233	5.3e-19	PFAM
MUTSd	264	591	9.4e-40	SMART
MUTSac	607	800	4.2e-84	SMART
Blast:MUTSac	808	866	4e-17	BLAST

Predicted Effect

possibly damaging
Transcript: ENSMUST00000190449
AA Change: H254L

PolyPhen 2 Score 0.937 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000140265
Gene: ENSMUSG00000005493
AA Change: H254L

Domain	Start	End	E-Value	Type
Pfam:MutS_II	1	127	3.3e-15	PFAM
MUTSd	158	485	9.4e-40	SMART
MUTSac	501	694	4.2e-84	SMART
Blast:MUTSac	702	760	5e-17	BLAST

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000191504

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000191606

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.5%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the DNA mismatch repair mutS family. This member is a meiosis-specific protein that is not involved in DNA mismatch correction, but is required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis I. This protein and MSH5 form a heterodimer which binds uniquely to a Holliday Junction and its developmental progenitor, thus provoking ADP-ATP exchange, and stabilizing the interaction between parental chromosomes during meiosis double-stranded break repair. [provided by RefSeq, Aug 2011]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit male and female sterility associated with failure to undergo pairing during meiosis. [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
4930550C14Rik	A	T	9: 53,425,530	M45L	probably benign	Het
4931440F15Rik	A	T	11: 29,825,454	M1K	probably null	Het
Abcb1a	T	A	5: 8,737,632	V978D	probably damaging	Het
Acsm4	T	C	7: 119,698,677	V179A	probably benign	Het
Agtr1a	C	A	13: 30,381,859	Y302*	probably null	Het
Akap9	T	C	5: 4,008,382	I1677T	probably damaging	Het
Ankk1	T	A	9: 49,415,930	M650L	probably benign	Het
Apod	T	A	16: 31,303,462	N65Y	probably damaging	Het
Bcl2l1	T	A	2: 152,782,258	N197Y	possibly damaging	Het
Brpf1	A	T	6: 113,315,111	I373F	probably damaging	Het
Car13	T	C	3: 14,661,555	V257A	probably damaging	Het
Ccdc150	A	T	1: 54,278,715	H271L	possibly damaging	Het
Cit	T	A	5: 115,997,549	I1836N	probably damaging	Het
Clec12b	A	G	6: 129,380,692	S68P	probably damaging	Het
Col4a4	A	G	1: 82,528,466	F298L	unknown	Het
Crct1	G	A	3: 93,014,786	Q15*	probably null	Het
Creld1	A	G	6: 113,492,247	E346G	probably benign	Het
Ctnnal1	T	A	4: 56,847,980	H53L	probably damaging	Het
Cyb5d1	T	C	11: 69,394,988	D74G	probably damaging	Het
Deptor	A	T	15: 55,212,278	S293C	probably damaging	Het
Dnajb12	A	G	10: 59,892,770	S187G	probably benign	Het
Duoxa2	G	T	2: 122,300,591	V78L	possibly damaging	Het
Fhod1	C	A	8: 105,347,811		probably benign	Het
Foxf2	C	T	13: 31,626,189	P37L	unknown	Het
Gabbr2	T	C	4: 46,875,675	N149S	probably damaging	Het
Gckr	G	T	5: 31,307,384	M344I	possibly damaging	Het
Gm10354	T	A	5: 14,976,208	H145L	probably benign	Het
Herc6	G	A	6: 57,600,060		probably null	Het
Igf1	A	T	10: 87,915,425	E161V	probably benign	Het
Ighv8-13	T	A	12: 115,765,648		probably benign	Het
Igkv6-14	A	T	6: 70,435,442	L12*	probably null	Het
Kpnb1	C	T	11: 97,177,334	S270N	possibly damaging	Het
Lingo1	A	G	9: 56,619,925	V460A	probably benign	Het
Lsm6	T	C	8: 78,813,082		probably null	Het
Mccc1	C	T	3: 35,995,917	G42E	probably benign	Het
Mga	A	G	2: 119,903,639	K323E	possibly damaging	Het
Mks1	A	G	11: 87,863,024	*562W	probably null	Het
Mrgpra4	T	A	7: 47,980,938	E305V	probably damaging	Het
Mthfsd	C	T	8: 121,098,998		probably null	Het
Myl12a	A	T	17: 70,996,803	F26L	possibly damaging	Het
Nedd4l	A	G	18: 65,165,605	S343G	probably damaging	Het
Nlgn1	T	A	3: 25,436,168	D465V	probably damaging	Het
Nlgn1	C	T	3: 25,436,343	V407I	possibly damaging	Het
Npsr1	T	C	9: 24,134,768	V61A	probably benign	Het
Nrxn2	A	G	19: 6,509,821	D160G	probably damaging	Het
Olfr1006	A	G	2: 85,674,320	F277S	probably damaging	Het
Olfr1370	T	C	13: 21,072,545	Y252C	probably damaging	Het
Olfr1461	A	C	19: 13,165,913	S300R	probably benign	Het
Olfr1467	G	T	19: 13,365,446	A273S	probably benign	Het
Olfr653	T	C	7: 104,580,197	Y184H	possibly damaging	Het
Pbx1	C	A	1: 168,195,881	R235L	probably damaging	Het
Pcnx4	T	C	12: 72,556,293	V443A	probably benign	Het
Pde7b	T	C	10: 20,547,942	T63A	probably benign	Het
Phf3	C	T	1: 30,820,827	G873D	probably damaging	Het
Phox2b	A	T	5: 67,098,854	Y30N	probably damaging	Het
Plch2	T	A	4: 154,996,233	I599F	possibly damaging	Het
Plekha8	A	G	6: 54,622,228	E249G	probably benign	Het
Pou2af1	T	A	9: 51,233,139	Y118N	possibly damaging	Het
Ppp3cc	T	A	14: 70,218,186	K489N	possibly damaging	Het
Sema4b	T	C	7: 80,216,829	L219P	probably damaging	Het
Slc6a5	T	G	7: 49,959,282	V745G	probably benign	Het
Slf2	A	G	19: 44,935,058	M104V	probably benign	Het
Slx1b	A	G	7: 126,692,529	V121A	probably benign	Het
Spen	T	A	4: 141,473,079	K2746*	probably null	Het
Stxbp5l	T	C	16: 37,188,634	Y681C	probably damaging	Het
Sv2b	T	C	7: 75,124,170	T518A	probably benign	Het
Tgm7	A	T	2: 121,096,389	H426Q	possibly damaging	Het
Tlx2	A	G	6: 83,069,919	F54S	probably benign	Het
Trp53bp2	A	T	1: 182,458,774	M1060L	probably benign	Het
Trpv5	T	A	6: 41,653,214	E647D	probably damaging	Het
Tut1	G	T	19: 8,959,308	K165N	possibly damaging	Het
Tyro3	A	G	2: 119,810,938	K543E	probably damaging	Het
Vmn2r69	T	A	7: 85,412,367	Y133F	probably damaging	Het
Zfhx4	T	A	3: 5,400,062	V1785D	possibly damaging	Het
Zfp451	A	G	1: 33,765,858	L1037P	probably damaging	Het
Zscan29	A	T	2: 121,160,911	F799I	possibly damaging	Het

Other mutations in Msh4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00862:Msh4	APN	3	153883735	missense	possibly damaging	0.88
IGL01098:Msh4	APN	3	153877982	splice site	probably benign
IGL01609:Msh4	APN	3	153897397	missense	probably damaging	1.00
IGL01785:Msh4	APN	3	153857507	missense	probably damaging	1.00
IGL01939:Msh4	APN	3	153857589	missense	probably damaging	1.00
IGL02022:Msh4	APN	3	153886956	missense	probably damaging	1.00
IGL02209:Msh4	APN	3	153888862	missense	probably damaging	1.00
IGL02224:Msh4	APN	3	153890185	missense	possibly damaging	0.94
IGL02240:Msh4	APN	3	153873674	missense	probably damaging	0.98
IGL02493:Msh4	APN	3	153877908	critical splice donor site	probably null
IGL02576:Msh4	APN	3	153867746	missense	probably damaging	1.00
IGL02616:Msh4	APN	3	153857523	missense	probably benign
IGL02812:Msh4	APN	3	153901400	splice site	probably benign
IGL02888:Msh4	APN	3	153896913	nonsense	probably null
IGL02992:Msh4	APN	3	153872325	missense	possibly damaging	0.79
IGL03191:Msh4	APN	3	153869608	missense	probably damaging	0.97
P0021:Msh4	UTSW	3	153888818	missense	probably damaging	1.00
R0057:Msh4	UTSW	3	153869681	missense	probably benign	0.16
R0057:Msh4	UTSW	3	153869681	missense	probably benign	0.16
R0368:Msh4	UTSW	3	153888825	missense	probably damaging	1.00
R0377:Msh4	UTSW	3	153896890	missense	probably benign	0.00
R0631:Msh4	UTSW	3	153866420	missense	probably benign	0.02
R0632:Msh4	UTSW	3	153896895	missense	probably damaging	1.00
R0677:Msh4	UTSW	3	153879367	missense	possibly damaging	0.69
R0909:Msh4	UTSW	3	153863504	missense	probably benign	0.00
R1081:Msh4	UTSW	3	153872358	missense	probably benign	0.06
R1463:Msh4	UTSW	3	153857570	missense	probably damaging	1.00
R1476:Msh4	UTSW	3	153863384	missense	probably damaging	1.00
R1669:Msh4	UTSW	3	153876720	missense	possibly damaging	0.47
R1733:Msh4	UTSW	3	153867767	missense	probably damaging	1.00
R1859:Msh4	UTSW	3	153905880	missense	probably benign
R2168:Msh4	UTSW	3	153867835	nonsense	probably null
R2378:Msh4	UTSW	3	153863477	missense	probably damaging	0.99
R2991:Msh4	UTSW	3	153905860	missense	probably benign
R3025:Msh4	UTSW	3	153863491	missense	probably damaging	1.00
R4604:Msh4	UTSW	3	153872283	missense	probably damaging	1.00
R5205:Msh4	UTSW	3	153866412	missense	probably damaging	1.00
R5285:Msh4	UTSW	3	153873713	missense	probably benign	0.03
R5766:Msh4	UTSW	3	153867840	missense	probably damaging	1.00
R5777:Msh4	UTSW	3	153863439	missense	probably benign	0.01
R5888:Msh4	UTSW	3	153867723	critical splice donor site	probably null
R7384:Msh4	UTSW	3	153888748	missense	probably benign	0.23
R7408:Msh4	UTSW	3	153876745	missense	probably benign	0.06
R7487:Msh4	UTSW	3	153863510	missense	probably damaging	1.00
R7503:Msh4	UTSW	3	153867750	missense	probably damaging	1.00
R7726:Msh4	UTSW	3	153866320	critical splice donor site	probably null
R7990:Msh4	UTSW	3	153896892	missense	probably damaging	1.00
R8097:Msh4	UTSW	3	153877908	critical splice donor site	probably null
R8805:Msh4	UTSW	3	153857633	missense	probably benign	0.00
R8814:Msh4	UTSW	3	153872320	missense	probably damaging	1.00
R8861:Msh4	UTSW	3	153901468	missense	probably benign	0.04
R8970:Msh4	UTSW	3	153869732	nonsense	probably null
R9010:Msh4	UTSW	3	153890182	missense	probably benign	0.30
R9338:Msh4	UTSW	3	153867807	missense	possibly damaging	0.55
R9598:Msh4	UTSW	3	153901511	missense	possibly damaging	0.93
R9780:Msh4	UTSW	3	153876705	missense	probably damaging	1.00
Z1177:Msh4	UTSW	3	153879368	missense	probably benign	0.00
Z1177:Msh4	UTSW	3	153901443	start gained	probably benign

Predicted Primers

PCR Primer
(F):5'- GACACCCTTGCTCATAGAAAAG -3'
(R):5'- CCACTATCTGGGCTTTGCTG -3'

Sequencing Primer
(F):5'- CCCTTGCTCATAGAAAAGACATG -3'
(R):5'- ATCTGGGCTTTGCTGATGTATAATTC -3'

Posted On

2015-11-11