Mutagenetix > Incidental Mutations

Incidental Mutation 'R1977:Mdc1'

221916

Institutional Source

Beutler Lab

Gene Symbol

Mdc1

Ensembl Gene

ENSMUSG00000061607

Gene Name

mediator of DNA damage checkpoint 1

Synonyms

NFBD1

MMRRC Submission

039990-MU

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.929) question?

Stock #

R1977 (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 35850930 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 912 (S912T)

Ref Sequence

ENSEMBL: ENSMUSP00000080949 (fasta)

Gene Model

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

Predicted Effect

probably benign
Transcript: ENSMUST00000082337
AA Change: S912T

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

SMART Domains

Protein: ENSMUSP00000080949
Gene: ENSMUSG00000061607
AA Change: S912T

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

0.0762

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.8%

Validation Efficiency

99% (66/67)

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: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsf3	G	T	8: 122,781,533	C256F	probably damaging	Het
Adgra2	T	A	8: 27,115,761	V647D	possibly damaging	Het
AI593442	A	T	9: 52,678,192	S28R	probably damaging	Het
Akr1c21	G	C	13: 4,574,212	G22R	probably damaging	Het
Ampd3	T	C	7: 110,803,162	W458R	probably damaging	Het
Arhgap23	G	T	11: 97,451,447	R185L	possibly damaging	Het
Arhgap45	A	T	10: 80,020,818	I67F	probably damaging	Het
Asah1	A	G	8: 41,343,517		probably null	Het
Atl2	A	G	17: 79,852,590	Y56H	probably damaging	Het
Carf	A	T	1: 60,146,136	I447F	probably damaging	Het
Crmp1	A	G	5: 37,276,283	N162S	probably damaging	Het
Cyp2a5	A	G	7: 26,835,922	E103G	probably benign	Het
Cyp2c40	T	C	19: 39,778,041	D370G	probably damaging	Het
Dhrs2	T	A	14: 55,234,655	M1K	probably null	Het
Dnah17	T	C	11: 118,112,591	E810G	possibly damaging	Het
E2f5	T	A	3: 14,587,356	I84N	probably damaging	Het
Eif2ak4	A	T	2: 118,461,757	K1185*	probably null	Het
Eif4ebp1	T	A	8: 27,275,101	M115K	probably damaging	Het
Evi5	A	T	5: 107,799,139	L505*	probably null	Het
Fbxw25	T	A	9: 109,652,856	Y254F	possibly damaging	Het
Gm7964	T	A	7: 83,757,352	F439Y	possibly damaging	Het
Gps1	A	G	11: 120,785,826	T124A	probably damaging	Het
Hopx	T	C	5: 77,117,616		probably benign	Het
Hoxd3	A	G	2: 74,744,276	S89G	possibly damaging	Het
Hrc	A	T	7: 45,336,214	D263V	probably damaging	Het
Hs6st3	T	C	14: 119,138,476	I21T	probably benign	Het
Izumo4	A	G	10: 80,703,121	Y106C	probably damaging	Het
Lama2	A	T	10: 26,990,800		probably null	Het
Lcorl	A	C	5: 45,775,420	S123R	probably null	Het
Lgr4	A	T	2: 110,011,928	I729F	probably damaging	Het
Lonp1	T	C	17: 56,615,068	T771A	possibly damaging	Het
Matn3	T	A	12: 8,961,110		probably benign	Het
Mgam	G	A	6: 40,664,880	V556I	probably benign	Het
Myom2	A	T	8: 15,085,263	I489F	possibly damaging	Het
Nfatc2	G	A	2: 168,504,459	T905I	possibly damaging	Het
Nme6	G	A	9: 109,835,341	R6Q	probably damaging	Het
Nr1h5	A	G	3: 102,947,817	S323P	probably damaging	Het
Nr4a3	C	A	4: 48,056,539	R364S	probably damaging	Het
Obox7	A	T	7: 14,664,398	D79V	probably damaging	Het
Olfr167	G	A	16: 19,514,836	P267S	probably damaging	Het
Olfr374	G	A	8: 72,109,854	G96D	probably benign	Het
Olfr435	T	A	6: 43,201,980	V112D	possibly damaging	Het
Pan2	T	C	10: 128,320,413	V1171A	probably damaging	Het
Parp8	T	A	13: 116,910,913	I208F	probably damaging	Het
Pdgfc	C	T	3: 81,209,245	T302I	probably damaging	Het
Pnpt1	A	G	11: 29,141,256	I337V	probably benign	Het
Polk	T	C	13: 96,489,228	E436G	probably damaging	Het
Pramel7	A	G	2: 87,491,121	V190A	probably benign	Het
Rplp2	T	C	7: 141,448,781		probably benign	Het
Sec23ip	T	A	7: 128,766,273	S670T	probably damaging	Het
Sgk2	A	G	2: 163,004,160	N207S	probably benign	Het
Sh2d2a	C	T	3: 87,851,816	Q242*	probably null	Het
Sh3pxd2b	A	C	11: 32,422,138	N435T	probably damaging	Het
Slc36a4	T	A	9: 15,734,210	V311D	probably damaging	Het
Stx17	G	A	4: 48,181,553	V241M	probably benign	Het
Taok3	A	T	5: 117,265,924	K721N	probably damaging	Het
Tbxas1	A	G	6: 38,948,641		probably benign	Het
Tmem87a	G	A	2: 120,374,504	A377V	probably benign	Het
Topaz1	C	T	9: 122,747,362	T6M	unknown	Het
Tspan8	A	G	10: 115,844,130	I217V	probably benign	Het
Vmn2r125	A	G	4: 156,354,591		probably null	Het
Vmn2r5	C	T	3: 64,504,221	E309K	probably damaging	Het
Wdr59	A	T	8: 111,458,638	C888S	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
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
R5888:Mdc1	UTSW	17	35847820	missense	probably benign	0.01
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
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'- AATAGAGATGTCCAAAGACTCACAG -3'
(R):5'- TGTCGTCTGGCAACTCAAGC -3'

Sequencing Primer
(F):5'- TGTCCAAAGACTCACAGAAGAG -3'
(R):5'- TCAAGCGGCCTAGTCAAAG -3'

Posted On

2014-08-25