Mutagenetix > Incidental Mutation

Incidental Mutation 'R8234:Dmpk'

637265

Institutional Source

Beutler Lab

Gene Symbol

Dmpk

Ensembl Gene

ENSMUSG00000030409

Gene Name

dystrophia myotonica-protein kinase

Synonyms

DM, Dm15

MMRRC Submission

Accession Numbers

NCBI RefSeq: NM_032418.2, NM_001190490.1, NM_001190491.1; MGI: 94906

Essential gene?

Possibly non essential (E-score: 0.395) question?

Stock #

R8234 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

19083849-19093821 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 19088123 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Asparagine at position 335 (K335N)

Ref Sequence

ENSEMBL: ENSMUSP00000104113 (fasta)

Gene Model

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

AlphaFold

P54265

Predicted Effect

probably benign
Transcript: ENSMUST00000032568
AA Change: K335N

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000032568
Gene: ENSMUSG00000030409
AA Change: K335N

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

probably benign
Transcript: ENSMUST00000108473
AA Change: K335N

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000104113
Gene: ENSMUSG00000030409
AA Change: K335N

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

probably benign
Transcript: ENSMUST00000108474

SMART Domains

Protein: ENSMUSP00000104114
Gene: ENSMUSG00000030409

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

probably benign
Transcript: ENSMUST00000154199
AA Change: K335N

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000118459
Gene: ENSMUSG00000030409
AA Change: K335N

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: 99.9%
3x: 99.8%
10x: 99.5%
20x: 98.8%

Validation Efficiency

100% (49/49)

MGI Phenotype

Strain: 3054407; 2182402
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: 48 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310035C23Rik	T	C	1: 105,753,510	S1180P	possibly damaging	Het
Abhd4	T	A	14: 54,261,676	M38K	probably benign	Het
Ackr1	T	A	1: 173,332,015	R312S	probably benign	Het
Agpat9	T	C	5: 100,857,210		probably null	Het
Akap9	T	C	5: 4,044,845	V2213A	probably benign	Het
Alox5	T	A	6: 116,413,874	R439W	probably damaging	Het
Atrn	A	T	2: 131,023,000		probably null	Het
Casd1	A	G	6: 4,601,209	N14S	probably damaging	Het
Cry2	T	C	2: 92,412,629	S542G	probably benign	Het
Cyb5rl	A	G	4: 107,068,738	Y39C	probably damaging	Het
Dnaic1	A	G	4: 41,625,221	D395G	probably benign	Het
Dock4	C	T	12: 40,834,838		probably null	Het
Fmo4	T	C	1: 162,805,188	D198G	probably damaging	Het
Foxc2	G	A	8: 121,118,038	R475Q	probably damaging	Het
Gipr	C	A	7: 19,164,608	G37V	unknown	Het
Gm15800	T	A	5: 121,339,544	N2843K	possibly damaging	Het
Gm2046	A	T	12: 87,973,738	I71L	noncoding transcript	Het
Hcn4	A	G	9: 58,844,150	D353G	unknown	Het
Hmcn1	C	T	1: 150,594,010	V4973M	possibly damaging	Het
Il20rb	C	T	9: 100,459,210	S281N	probably benign	Het
Kcnh4	A	T	11: 100,752,267	N391K	possibly damaging	Het
Kitl	A	G	10: 100,051,846	T6A	probably damaging	Het
Krt36	A	G	11: 100,104,201	Y182H	probably damaging	Het
Lrp1b	T	G	2: 41,312,656	I1262L		Het
Mtf1	A	G	4: 124,844,246	E644G	probably benign	Het
Mtx2	A	G	2: 74,869,362	Y159C	probably damaging	Het
Nags	C	T	11: 102,148,998	S504F	probably damaging	Het
Ncam1	A	T	9: 49,545,223	F475L	probably damaging	Het
Nipal2	G	T	15: 34,600,032	T213N	possibly damaging	Het
Olfr1098	A	G	2: 86,922,969	S188P	probably damaging	Het
Olfr554	T	A	7: 102,640,471	L75Q	probably damaging	Het
Pkm	T	C	9: 59,670,599	V233A	possibly damaging	Het
Pros1	T	A	16: 62,928,177	I671N	possibly damaging	Het
Rasd1	T	C	11: 59,964,292	I121V	probably damaging	Het
Samhd1	A	G	2: 157,116,350		probably null	Het
Serpinb9f	A	T	13: 33,325,915	Y30F	probably benign	Het
Slc5a10	T	C	11: 61,673,281	I543V	probably benign	Het
Stat5a	A	G	11: 100,879,303	I469V	possibly damaging	Het
Sugct	T	C	13: 16,857,874	E431G	probably benign	Het
Tecr	C	A	8: 83,573,251	R133L	possibly damaging	Het
Tiparp	A	G	3: 65,531,581	N106S	probably benign	Het
Triml1	T	C	8: 43,141,248	S49G	probably benign	Het
Trpm3	T	A	19: 22,715,276	S244T	possibly damaging	Het
Ttn	T	C	2: 76,722,980	D31055G	probably damaging	Het
Vcp	A	T	4: 42,985,242	I369N	probably damaging	Het
Vmn2r110	A	C	17: 20,584,429	N76K	probably benign	Het
Vmn2r12	T	C	5: 109,086,208	T713A	probably benign	Het
Vmn2r17	A	T	5: 109,453,369	K844N	probably benign	Het

Other mutations in Dmpk

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02198:Dmpk	APN	7	19088192	missense	probably damaging	0.98
IGL02874:Dmpk	APN	7	19087001	missense	possibly damaging	0.75
IGL02942:Dmpk	APN	7	19092241	missense	probably damaging	0.99
IGL03081:Dmpk	APN	7	19087533	missense	probably damaging	1.00
IGL03258:Dmpk	APN	7	19092206	critical splice acceptor site	probably null
IGL03302:Dmpk	APN	7	19086486	splice site	probably benign
P0008:Dmpk	UTSW	7	19088062	missense	possibly damaging	0.89
R0388:Dmpk	UTSW	7	19084077	unclassified	probably benign
R0961:Dmpk	UTSW	7	19087270	missense	probably damaging	0.99
R3103:Dmpk	UTSW	7	19087654	missense	probably damaging	1.00
R3157:Dmpk	UTSW	7	19093019	missense	probably benign	0.00
R3158:Dmpk	UTSW	7	19093019	missense	probably benign	0.00
R3159:Dmpk	UTSW	7	19093019	missense	probably benign	0.00
R3498:Dmpk	UTSW	7	19086381	missense	probably damaging	1.00
R4696:Dmpk	UTSW	7	19088214	missense	probably damaging	1.00
R4830:Dmpk	UTSW	7	19087528	missense	probably damaging	1.00
R4991:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5156:Dmpk	UTSW	7	19084125	missense	probably damaging	1.00
R5169:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5170:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5171:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5172:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5198:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5200:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5202:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5205:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5383:Dmpk	UTSW	7	19088019	missense	probably benign	0.05
R5449:Dmpk	UTSW	7	19090991	missense	probably benign	0.18
R5639:Dmpk	UTSW	7	19092600	missense	probably benign	0.22
R5874:Dmpk	UTSW	7	19092082	intron	probably benign
R6939:Dmpk	UTSW	7	19088224	missense	probably damaging	0.97
R7133:Dmpk	UTSW	7	19087307	missense	probably damaging	1.00
R7352:Dmpk	UTSW	7	19086072	missense	probably damaging	0.98
R8032:Dmpk	UTSW	7	19088053	missense	possibly damaging	0.63
R8886:Dmpk	UTSW	7	19091961	unclassified	probably benign
R9052:Dmpk	UTSW	7	19087689	missense	probably damaging	0.99
R9235:Dmpk	UTSW	7	19088216	missense	probably damaging	1.00
R9420:Dmpk	UTSW	7	19091021	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- GACTTAGTGGCTTGTGCTCC -3'
(R):5'- TTTTATGGAAGAGGCTAGGGAAGTC -3'

Sequencing Primer
(F):5'- TGGGAAACAGAACCTTGATCACTCTG -3'
(R):5'- GGAAGTCCCCTCAACGGATCAG -3'

Posted On

2020-07-13