Mutagenetix > Incidental Mutation

Incidental Mutation 'R5888:Mdc1'

457840

Institutional Source

Beutler Lab

Gene Symbol

Mdc1

Ensembl Gene

ENSMUSG00000061607

Gene Name

mediator of DNA damage checkpoint 1

Synonyms

NFBD1

MMRRC Submission

044089-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.936) question?

Stock #

R5888 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

35841515-35859670 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 35847820 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 364 (V364E)

Ref Sequence

ENSEMBL: ENSMUSP00000080949 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000082337] [ENSMUST00000174124]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000082337
AA Change: V364E

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000080949
Gene: ENSMUSG00000061607
AA Change: V364E

Domain	Start	End	E-Value	Type
low complexity region	12	18	N/A	INTRINSIC
FHA	53	105	5.63e-9	SMART
low complexity region	194	215	N/A	INTRINSIC
low complexity region	854	870	N/A	INTRINSIC
low complexity region	969	987	N/A	INTRINSIC
low complexity region	1008	1022	N/A	INTRINSIC
internal_repeat_1	1027	1115	6.7e-11	PROSPERO
internal_repeat_2	1030	1141	2.36e-9	PROSPERO
internal_repeat_1	1266	1354	6.7e-11	PROSPERO
internal_repeat_2	1298	1417	2.36e-9	PROSPERO
low complexity region	1422	1445	N/A	INTRINSIC
low complexity region	1457	1477	N/A	INTRINSIC
BRCT	1502	1579	1.66e-1	SMART
BRCT	1612	1691	2.45e1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000174124

SMART Domains

Protein: ENSMUSP00000133568
Gene: ENSMUSG00000061607

Domain	Start	End	E-Value	Type
low complexity region	12	18	N/A	INTRINSIC
FHA	53	105	5.63e-9	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000225192

Meta Mutation Damage Score

0.0816

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.9%

Validation Efficiency

94% (96/102)

MGI Phenotype

FUNCTION: The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 7 divergent copies of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. Mice with mutations in this gene exhibit growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects, and radiation sensitivity. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutant mice are smaller and display increased susceptibility to ionizing radiation, male infertility, T and B cell abnormalities, and increased genomic instability. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700029P11Rik	T	C	15: 81,980,671	S38P	probably benign	Het
Adcy1	T	A	11: 7,139,095	V503E	possibly damaging	Het
Alk	C	A	17: 71,874,943	V1362L	probably damaging	Het
Ankrd55	T	A	13: 112,355,919	I208N	possibly damaging	Het
Asap2	T	A	12: 21,218,190	I319N	probably damaging	Het
Atp11b	T	C	3: 35,837,547	I1036T	probably benign	Het
B4gat1	T	C	19: 5,039,532	F186L	probably benign	Het
C3	T	A	17: 57,214,831	T1079S	probably damaging	Het
Cacul1	G	T	19: 60,537,464	T287K	possibly damaging	Het
Cbr3	G	C	16: 93,690,726	G266R	probably damaging	Het
Cd63	T	A	10: 128,912,291		probably null	Het
Chd7	G	A	4: 8,866,382	M851I	probably damaging	Het
Chst13	T	A	6: 90,309,572	H136L	probably benign	Het
Cyp2d22	T	C	15: 82,373,813	T179A	probably benign	Het
Dclre1b	A	T	3: 103,803,737	V286E	probably damaging	Het
Defb45	G	A	2: 152,593,234		probably benign	Het
Dlg1	T	C	16: 31,791,886		probably null	Het
Dock3	A	G	9: 107,023,803	V321A	probably benign	Het
Dytn	A	T	1: 63,677,237	V59E	possibly damaging	Het
Eif2ak1	A	G	5: 143,886,915	I393M	probably damaging	Het
Fam83g	A	T	11: 61,702,594	E318V	probably benign	Het
Fbxo34	T	A	14: 47,529,719	F179I	probably damaging	Het
Fmo5	T	A	3: 97,641,725	Y230N	probably benign	Het
Fzd9	T	G	5: 135,249,463		probably null	Het
Gata2	T	C	6: 88,200,740	S251P	probably benign	Het
Gigyf1	A	G	5: 137,525,697	D1043G	probably damaging	Het
Gm10260	G	A	13: 97,760,393	R66*	probably null	Het
Gm10322	T	A	10: 59,616,303	S81T	probably benign	Het
Gm11639	T	C	11: 104,721,401		probably benign	Het
Gm15517	A	T	7: 44,260,642		probably benign	Het
Haus4	T	C	14: 54,544,219	T232A	probably benign	Het
Hgfac	A	T	5: 35,045,407	H417L	probably damaging	Het
Iqgap2	T	C	13: 95,635,610	K1354E	possibly damaging	Het
Kcnk12	C	A	17: 87,746,649	R195L	probably benign	Het
Kcnn2	A	T	18: 45,592,345	I303F	probably damaging	Het
Kcnt1	T	C	2: 25,908,110	F879S	probably damaging	Het
Kndc1	T	C	7: 139,895,217	F11L	probably benign	Het
Kpna7	A	G	5: 144,989,795	F449S	probably damaging	Het
Krt77	G	T	15: 101,865,453	N255K	probably benign	Het
Lair1	A	T	7: 4,010,845	D134E	probably damaging	Het
Loxhd1	T	C	18: 77,402,515	V1318A	probably damaging	Het
March10	A	T	11: 105,402,146	V145D	possibly damaging	Het
Mcpt1	T	A	14: 56,019,512	M169K	probably benign	Het
Mfsd11	T	C	11: 116,871,384	F270S	probably damaging	Het
Mfsd4b2	T	G	10: 39,922,035	D108A	probably benign	Het
Mink1	A	T	11: 70,610,059		probably benign	Het
Mmp25	T	C	17: 23,631,074	Y504C	probably damaging	Het
Ms4a13	C	T	19: 11,191,506	V52I	probably benign	Het
Msh4	C	T	3: 153,867,723		probably null	Het
Muc5b	T	G	7: 141,858,421	S1701R	unknown	Het
Naalad2	A	T	9: 18,330,641	S656T	probably benign	Het
Ncapd2	T	C	6: 125,187,089	Y64C	probably damaging	Het
Ncapg2	T	A	12: 116,425,800	S347T	possibly damaging	Het
Nipal4	T	C	11: 46,151,339	T172A	probably damaging	Het
Nrros	T	C	16: 32,143,087	K652R	probably benign	Het
Nrxn3	G	T	12: 89,512,085	A983S	possibly damaging	Het
Olfr1084	A	C	2: 86,639,144	L188R	probably damaging	Het
Olfr1187-ps1	T	C	2: 88,540,244		noncoding transcript	Het
Olfr1220	T	A	2: 89,097,925	M1L	probably damaging	Het
Olfr1249	T	A	2: 89,630,799	Y33F	probably damaging	Het
Olfr1283	T	C	2: 111,368,743	M37T	probably benign	Het
Olfr631	A	G	7: 103,929,032	T70A	possibly damaging	Het
Olfr938	A	T	9: 39,077,967	Y259*	probably null	Het
P2rx4	T	A	5: 122,719,165	S155T	probably benign	Het
P2rx4	T	G	5: 122,727,208	Y299D	probably damaging	Het
Pcsk6	A	T	7: 66,043,624	L7F	probably null	Het
Pdss2	T	C	10: 43,221,797		silent	Het
Pfkl	A	G	10: 77,991,370	V494A	possibly damaging	Het
Prep	G	T	10: 45,067,364	D12Y	possibly damaging	Het
Prg4	A	G	1: 150,452,350	F188S	probably damaging	Het
Ripor3	T	C	2: 167,997,287	Y98C	probably damaging	Het
Rnf216	T	A	5: 143,068,314		probably null	Het
Rnf24	A	G	2: 131,322,245		probably benign	Het
Scn3a	A	G	2: 65,497,398	M916T	probably benign	Het
Scnm1	T	C	3: 95,130,285	I157V	probably benign	Het
Sh2b3	C	G	5: 121,829,021	R10P	possibly damaging	Het
Slc25a27	T	C	17: 43,649,694	D211G	probably damaging	Het
Slc36a4	A	T	9: 15,727,028	Y250F	probably damaging	Het
Slc4a1	T	A	11: 102,356,525	E448V	probably damaging	Het
Slit1	C	A	19: 41,743,296	C38F	probably damaging	Het
Spock3	T	A	8: 63,355,300	N410K	unknown	Het
Supt20	G	T	3: 54,712,207	W370L	probably benign	Het
Tas2r139	T	A	6: 42,141,496	N187K	probably damaging	Het
Tbc1d9b	G	A	11: 50,140,484	V111I	probably benign	Het
Thsd7b	T	A	1: 130,210,320	Y1578*	probably null	Het
Tln2	T	A	9: 67,229,403	I1267F	probably damaging	Het
Tnk2	G	A	16: 32,671,367	V363I	probably damaging	Het
Ttc32	A	G	12: 9,035,870	K139R	possibly damaging	Het
Vmn1r30	G	C	6: 58,435,565	T94S	possibly damaging	Het
Vmn1r90	G	A	7: 14,561,855	T106I	probably damaging	Het
Zfp677	T	A	17: 21,398,258	C526S	probably damaging	Het
Zfp831	T	G	2: 174,643,627	S32A	probably benign	Het

Other mutations in Mdc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01473:Mdc1	APN	17	35848020	missense	probably benign	0.04
IGL01662:Mdc1	APN	17	35852505	missense	probably benign	0.00
IGL01931:Mdc1	APN	17	35848231	missense	probably benign	0.00
IGL02542:Mdc1	APN	17	35853156	missense	probably damaging	0.96
IGL02823:Mdc1	APN	17	35852923	missense	probably damaging	0.99
IGL03411:Mdc1	APN	17	35853126	missense	probably benign	0.06
IGL02799:Mdc1	UTSW	17	35846191	missense	possibly damaging	0.86
PIT4362001:Mdc1	UTSW	17	35844469	missense	possibly damaging	0.72
R0054:Mdc1	UTSW	17	35849033	missense	probably benign	0.00
R0129:Mdc1	UTSW	17	35854445	missense	probably benign	0.04
R0131:Mdc1	UTSW	17	35852581	missense	probably damaging	0.99
R0131:Mdc1	UTSW	17	35852581	missense	probably damaging	0.99
R0132:Mdc1	UTSW	17	35852581	missense	probably damaging	0.99
R1406:Mdc1	UTSW	17	35853532	missense	probably benign	0.10
R1406:Mdc1	UTSW	17	35853532	missense	probably benign	0.10
R1597:Mdc1	UTSW	17	35845866	missense	probably damaging	1.00
R1721:Mdc1	UTSW	17	35847826	missense	possibly damaging	0.85
R1888:Mdc1	UTSW	17	35854225	missense	probably benign	0.03
R1888:Mdc1	UTSW	17	35854225	missense	probably benign	0.03
R1912:Mdc1	UTSW	17	35844538	missense	probably benign	0.00
R1912:Mdc1	UTSW	17	35850811	missense	probably benign	0.19
R1977:Mdc1	UTSW	17	35850930	missense	probably benign	0.01
R2121:Mdc1	UTSW	17	35847943	missense	probably benign	0.03
R2122:Mdc1	UTSW	17	35847943	missense	probably benign	0.03
R2357:Mdc1	UTSW	17	35847445	missense	probably benign	0.00
R2842:Mdc1	UTSW	17	35848794	missense	probably benign	0.01
R2851:Mdc1	UTSW	17	35849010	missense	probably benign	0.04
R2852:Mdc1	UTSW	17	35849010	missense	probably benign	0.04
R2964:Mdc1	UTSW	17	35853637	missense	possibly damaging	0.72
R2996:Mdc1	UTSW	17	35847893	unclassified	probably benign
R3752:Mdc1	UTSW	17	35845929	missense	probably damaging	1.00
R4234:Mdc1	UTSW	17	35848824	missense	probably benign	0.00
R4641:Mdc1	UTSW	17	35857469	missense	probably benign	0.09
R4706:Mdc1	UTSW	17	35852779	missense	probably damaging	0.99
R4809:Mdc1	UTSW	17	35849101	critical splice donor site	probably null
R4833:Mdc1	UTSW	17	35850394	missense	probably benign	0.20
R5032:Mdc1	UTSW	17	35850589	missense	probably benign	0.00
R5047:Mdc1	UTSW	17	35847844	missense	probably benign	0.00
R5086:Mdc1	UTSW	17	35848630	missense	probably benign	0.00
R5172:Mdc1	UTSW	17	35853090	missense	probably benign	0.00
R5254:Mdc1	UTSW	17	35847922	missense	probably benign	0.00
R5473:Mdc1	UTSW	17	35848060	missense	probably benign	0.01
R5550:Mdc1	UTSW	17	35845884	missense	possibly damaging	0.64
R5561:Mdc1	UTSW	17	35848546	missense	probably benign	0.00
R6020:Mdc1	UTSW	17	35848633	missense	probably benign	0.04
R6020:Mdc1	UTSW	17	35857572	missense	probably benign	0.01
R6219:Mdc1	UTSW	17	35850674	missense	probably benign	0.10
R7053:Mdc1	UTSW	17	35846326	missense	probably benign	0.00
R7073:Mdc1	UTSW	17	35854068	missense	probably benign	0.18
R7077:Mdc1	UTSW	17	35845947	missense	probably damaging	0.97
R7424:Mdc1	UTSW	17	35853309	missense	probably benign	0.04
R7443:Mdc1	UTSW	17	35850820	missense	probably damaging	0.98
R7467:Mdc1	UTSW	17	35844556	missense	probably benign	0.29
R7549:Mdc1	UTSW	17	35848857	missense	probably null	0.04
R7655:Mdc1	UTSW	17	35850881	missense	probably benign	0.01
R7656:Mdc1	UTSW	17	35850881	missense	probably benign	0.01
R7960:Mdc1	UTSW	17	35850678	nonsense	probably null
R8350:Mdc1	UTSW	17	35848299	missense	probably benign	0.00
R8450:Mdc1	UTSW	17	35848299	missense	probably benign	0.00
R8688:Mdc1	UTSW	17	35850491	missense	probably benign	0.10
R8726:Mdc1	UTSW	17	35847583	missense	probably benign	0.04
R8919:Mdc1	UTSW	17	35847951	missense	probably benign	0.00
R8961:Mdc1	UTSW	17	35848515	missense	probably benign	0.10
R9324:Mdc1	UTSW	17	35853366	missense	probably benign	0.10
R9363:Mdc1	UTSW	17	35851127	missense	probably benign	0.00
R9385:Mdc1	UTSW	17	35850504	missense	probably benign	0.00
RF025:Mdc1	UTSW	17	35854407	critical splice acceptor site	probably benign
X0022:Mdc1	UTSW	17	35850937	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- ACGAAGATCACAAACCTGGG -3'
(R):5'- TGGCTTTGTTCTACAAGGACCTG -3'

Sequencing Primer
(F):5'- AAACCTGGGTTTGCGGAC -3'
(R):5'- CTACAAGGACCTGTGGTTGGGAC -3'

Posted On

2017-02-15