Mutagenetix > Incidental Mutation

Incidental Mutation 'R8032:Dmpk'

618018

Institutional Source

Beutler Lab

Gene Symbol

Dmpk

Ensembl Gene

ENSMUSG00000030409

Gene Name

dystrophia myotonica-protein kinase

Synonyms

Dm15, DM

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.421) question?

Stock #

R8032 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

18817774-18827746 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 18821978 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 312 (D312G)

Ref Sequence

ENSEMBL: ENSMUSP00000104113 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000032568] [ENSMUST00000108473] [ENSMUST00000108474] [ENSMUST00000122999] [ENSMUST00000154199]

AlphaFold

P54265

Predicted Effect

possibly damaging
Transcript: ENSMUST00000032568
AA Change: D312G

PolyPhen 2 Score 0.680 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000032568
Gene: ENSMUSG00000030409
AA Change: D312G

Domain	Start	End	E-Value	Type
low complexity region	5	31	N/A	INTRINSIC
S_TKc	71	339	6.5e-87	SMART
S_TK_X	340	407	3.6e-11	SMART
Pfam:DMPK_coil	472	532	2.8e-25	PFAM
low complexity region	590	613	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000108473
AA Change: D312G

PolyPhen 2 Score 0.630 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000104113
Gene: ENSMUSG00000030409
AA Change: D312G

Domain	Start	End	E-Value	Type
low complexity region	5	31	N/A	INTRINSIC
S_TKc	71	339	1.36e-84	SMART
S_TK_X	340	407	7.5e-9	SMART
Pfam:DMPK_coil	472	532	2.2e-28	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000108474
AA Change: D312G

PolyPhen 2 Score 0.859 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000104114
Gene: ENSMUSG00000030409
AA Change: D312G

Domain	Start	End	E-Value	Type
low complexity region	5	31	N/A	INTRINSIC
S_TKc	71	336	2.57e-76	SMART
Pfam:DMPK_coil	446	506	2.4e-28	PFAM
low complexity region	564	587	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000122999

SMART Domains

Protein: ENSMUSP00000123516
Gene: ENSMUSG00000030409

Domain	Start	End	E-Value	Type
low complexity region	5	31	N/A	INTRINSIC
PDB:2VD5\|B	32	139	3e-62	PDB
SCOP:d1koba_	44	139	3e-21	SMART
Blast:S_TKc	71	139	7e-36	BLAST

Predicted Effect

possibly damaging
Transcript: ENSMUST00000154199
AA Change: D312G

PolyPhen 2 Score 0.830 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000118459
Gene: ENSMUSG00000030409
AA Change: D312G

Domain	Start	End	E-Value	Type
low complexity region	5	31	N/A	INTRINSIC
S_TKc	71	339	1.36e-84	SMART
S_TK_X	340	402	5.3e-9	SMART
Pfam:DMPK_coil	467	527	2.3e-28	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.4%

Validation Efficiency

MGI Phenotype

FUNCTION: The protein encoded by this gene is a serine/threonine protein kinase that contains coiled-coil and C-terminal membrane association domains. In the embryonic mouse, it is found in cardiac and skeletal myocytes where it appears to play a role in myogenesis. In adults, the transcript is localized to several tissues including brain, heart, and skeletal and smooth muscle, and a function in cytoskeletal remodeling has been described. Transcripts with expanded CUG repeats in the 3' untranslated region mediate alternative splicing of several genes and sequester RNA binding proteins and RNA transcripts that contain CAG repeats, resulting in myotonic dystrophy, an autosomal dominant neuromuscular disorder. Alternative splicing results in multiple protein coding and non-coding transcript variants. [provided by RefSeq, Oct 2014]
PHENOTYPE: Homozygotes for a null mutation exhibit abnormal sodium channel gating in cardiac myocytes, cardiac conduction defects, and late-onset progressive skeletal myopathy. Homozygotes for a second null mutation do not develop skeletal myopathy but do have abnormal muscle intracellular calcium levels. [provided by MGI curators]

Allele List at MGI

All alleles(4) : Targeted(4)

Other mutations in this stock

Total: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actrt2	T	A	4: 154,751,955 (GRCm39)	E60D	probably benign	Het
Adamts12	T	C	15: 11,259,189 (GRCm39)		probably null	Het
Ak9	T	A	10: 41,300,616 (GRCm39)	C1609S	unknown	Het
Aox1	A	T	1: 58,389,442 (GRCm39)	Y1147F	probably benign	Het
Atf7ip	T	C	6: 136,542,110 (GRCm39)	F615L	probably benign	Het
BC005624	A	G	2: 30,865,901 (GRCm39)		probably null	Het
BC024063	T	A	10: 81,943,738 (GRCm39)	M33K	probably benign	Het
Bmpr2	T	A	1: 59,906,502 (GRCm39)	S532T	probably benign	Het
Cast	G	A	13: 74,883,360 (GRCm39)	Q292*	probably null	Het
Ccdc7a	G	T	8: 129,551,864 (GRCm39)	H1249N	unknown	Het
Cd177	C	T	7: 24,455,594 (GRCm39)	W309*	probably null	Het
Col15a1	T	C	4: 47,288,108 (GRCm39)	I4T	unknown	Het
Cyp2c39	A	G	19: 39,499,426 (GRCm39)	I38V	probably benign	Het
Dnah1	T	C	14: 30,993,505 (GRCm39)	D2892G	probably damaging	Het
Dnah10	G	A	5: 124,823,676 (GRCm39)	D566N	probably damaging	Het
Dsc2	C	T	18: 20,165,331 (GRCm39)	G881R	possibly damaging	Het
Exd2	T	A	12: 80,536,427 (GRCm39)	D352E	probably benign	Het
Fgf8	A	T	19: 45,725,676 (GRCm39)	L187Q	probably damaging	Het
Frrs1	A	G	3: 116,672,009 (GRCm39)	I36V	probably benign	Het
Gga2	A	T	7: 121,620,210 (GRCm39)		probably null	Het
Gigyf2	C	G	1: 87,334,735 (GRCm39)	H249D	unknown	Het
Gli2	A	T	1: 118,763,900 (GRCm39)	M1417K	probably damaging	Het
Gm10801	C	CGTA	2: 98,494,152 (GRCm39)		probably null	Het
Gm49380	A	T	9: 44,023,000 (GRCm39)	I416N	probably damaging	Het
Gpr137	T	C	19: 6,919,480 (GRCm39)	T16A	unknown	Het
Grid1	T	A	14: 35,045,316 (GRCm39)	D386E	probably benign	Het
Grm3	A	G	5: 9,562,272 (GRCm39)	V526A	probably benign	Het
Havcr2	A	T	11: 46,370,118 (GRCm39)	I231F	probably damaging	Het
Icam5	C	A	9: 20,944,514 (GRCm39)	R72S	probably benign	Het
Ighv9-2	T	A	12: 114,072,764 (GRCm39)	I70L	possibly damaging	Het
Inpp5e	C	T	2: 26,286,865 (GRCm39)	S119N		Het
Kash5	CGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTC	CGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTCAGGCTC	7: 44,837,608 (GRCm39)		probably benign	Het
Kash5	TCAGGC	TCAGGCACAGGC	7: 44,837,630 (GRCm39)		probably benign	Het
Kxd1	T	A	8: 70,966,791 (GRCm39)	D110V	possibly damaging	Het
Mbd4	A	G	6: 115,821,594 (GRCm39)	S474P	probably damaging	Het
Meaf6	C	A	4: 124,996,795 (GRCm39)	H168Q	unknown	Het
Nek2	T	C	1: 191,558,457 (GRCm39)	L254S	probably damaging	Het
Nhej1	T	C	1: 75,007,959 (GRCm39)	D104G	probably benign	Het
Nmnat3	A	G	9: 98,292,271 (GRCm39)	E172G	probably benign	Het
Npm3	A	T	19: 45,736,682 (GRCm39)	D152E	probably benign	Het
Nsd1	A	T	13: 55,458,196 (GRCm39)	K2103M	probably damaging	Het
Ntrk3	C	T	7: 78,005,807 (GRCm39)	R518H	probably damaging	Het
Nup210	T	A	6: 91,051,331 (GRCm39)	T351S	probably benign	Het
Or10h5	T	A	17: 33,434,924 (GRCm39)	R131S	possibly damaging	Het
Or9g19	A	G	2: 85,600,210 (GRCm39)	I22V	probably benign	Het
Otof	T	A	5: 30,619,142 (GRCm39)	M1L	probably benign	Het
Pacs2	T	A	12: 113,025,278 (GRCm39)	Y477N	probably damaging	Het
Panx3	A	G	9: 37,572,966 (GRCm39)	Y195H	probably damaging	Het
Pcsk5	T	C	19: 17,692,151 (GRCm39)	R178G	probably damaging	Het
Pde7a	A	G	3: 19,314,429 (GRCm39)	S56P	possibly damaging	Het
Prcp	T	G	7: 92,577,906 (GRCm39)	C392G	probably damaging	Het
Prkdc	A	G	16: 15,597,315 (GRCm39)	K2825R	probably benign	Het
Ptpn12	T	C	5: 21,203,041 (GRCm39)	H579R	probably benign	Het
Rbl1	A	T	2: 157,029,918 (GRCm39)	Y468*	probably null	Het
Rbmxl2	A	G	7: 106,809,429 (GRCm39)	Y238C	probably damaging	Het
Scgb2b20	A	T	7: 33,065,724 (GRCm39)	M1K	probably null	Het
Slc25a18	G	A	6: 120,769,452 (GRCm39)	G237D	probably damaging	Het
Slc9a3	G	A	13: 74,305,763 (GRCm39)	G260D	probably damaging	Het
Sorcs1	A	T	19: 50,463,846 (GRCm39)	S201R	probably benign	Het
Strip1	A	C	3: 107,525,394 (GRCm39)	D547E	probably damaging	Het
Thsd7a	C	T	6: 12,555,287 (GRCm39)	C199Y		Het
Top1mt	A	G	15: 75,540,572 (GRCm39)	V233A	probably damaging	Het
Tpp2	C	G	1: 44,014,628 (GRCm39)	P656A	possibly damaging	Het
Ttc1	A	T	11: 43,628,806 (GRCm39)	L193Q	probably damaging	Het
Ttll4	T	A	1: 74,735,632 (GRCm39)	D1013E	possibly damaging	Het
Unc5a	T	C	13: 55,144,299 (GRCm39)	V208A	possibly damaging	Het
Vmn1r185	C	A	7: 26,310,558 (GRCm39)	V316F	probably benign	Het
Vmn2r112	T	A	17: 22,822,375 (GRCm39)	V351E	probably benign	Het
Wdfy4	T	A	14: 32,751,043 (GRCm39)	K2391*	probably null	Het
Zfhx3	T	C	8: 109,677,854 (GRCm39)	V2968A	possibly damaging	Het
Zfp551	G	A	7: 12,152,487 (GRCm39)	A82V	possibly damaging	Het

Other mutations in Dmpk

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02198:Dmpk	APN	7	18,822,117 (GRCm39)	missense	probably damaging	0.98
IGL02874:Dmpk	APN	7	18,820,926 (GRCm39)	missense	possibly damaging	0.75
IGL02942:Dmpk	APN	7	18,826,166 (GRCm39)	missense	probably damaging	0.99
IGL03081:Dmpk	APN	7	18,821,458 (GRCm39)	missense	probably damaging	1.00
IGL03258:Dmpk	APN	7	18,826,131 (GRCm39)	critical splice acceptor site	probably null
IGL03302:Dmpk	APN	7	18,820,411 (GRCm39)	splice site	probably benign
P0008:Dmpk	UTSW	7	18,821,987 (GRCm39)	missense	possibly damaging	0.89
R0388:Dmpk	UTSW	7	18,818,002 (GRCm39)	unclassified	probably benign
R0961:Dmpk	UTSW	7	18,821,195 (GRCm39)	missense	probably damaging	0.99
R3103:Dmpk	UTSW	7	18,821,579 (GRCm39)	missense	probably damaging	1.00
R3157:Dmpk	UTSW	7	18,826,944 (GRCm39)	missense	probably benign	0.00
R3158:Dmpk	UTSW	7	18,826,944 (GRCm39)	missense	probably benign	0.00
R3159:Dmpk	UTSW	7	18,826,944 (GRCm39)	missense	probably benign	0.00
R3498:Dmpk	UTSW	7	18,820,306 (GRCm39)	missense	probably damaging	1.00
R4696:Dmpk	UTSW	7	18,822,139 (GRCm39)	missense	probably damaging	1.00
R4830:Dmpk	UTSW	7	18,821,453 (GRCm39)	missense	probably damaging	1.00
R4991:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5156:Dmpk	UTSW	7	18,818,050 (GRCm39)	missense	probably damaging	1.00
R5169:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5170:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5171:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5172:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5198:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5200:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5202:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5205:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5383:Dmpk	UTSW	7	18,821,944 (GRCm39)	missense	probably benign	0.05
R5449:Dmpk	UTSW	7	18,824,916 (GRCm39)	missense	probably benign	0.18
R5639:Dmpk	UTSW	7	18,826,525 (GRCm39)	missense	probably benign	0.22
R5874:Dmpk	UTSW	7	18,826,007 (GRCm39)	intron	probably benign
R6939:Dmpk	UTSW	7	18,822,149 (GRCm39)	missense	probably damaging	0.97
R7133:Dmpk	UTSW	7	18,821,232 (GRCm39)	missense	probably damaging	1.00
R7352:Dmpk	UTSW	7	18,819,997 (GRCm39)	missense	probably damaging	0.98
R8234:Dmpk	UTSW	7	18,822,048 (GRCm39)	missense	probably benign	0.00
R8886:Dmpk	UTSW	7	18,825,886 (GRCm39)	unclassified	probably benign
R9052:Dmpk	UTSW	7	18,821,614 (GRCm39)	missense	probably damaging	0.99
R9235:Dmpk	UTSW	7	18,822,141 (GRCm39)	missense	probably damaging	1.00
R9420:Dmpk	UTSW	7	18,824,946 (GRCm39)	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- ACTTAGTGGCTTGTGCTCC -3'
(R):5'- CGAAATTGCATGTGTCCGTGG -3'

Sequencing Primer
(F):5'- CACAGACTATTGTGTGCTGCCATG -3'
(R):5'- TGGCACCCTCGAAGTCTG -3'

Posted On

2020-01-23