Mutagenetix > Incidental Mutations

Incidental Mutation 'R1469:Dctn1'

500273

Institutional Source

Beutler Lab

Gene Symbol

Dctn1

Ensembl Gene

ENSMUSG00000031865

Gene Name

dynactin 1

Synonyms

p150, Glued, p150

MMRRC Submission

039522-MU

Accession Numbers

Ncbi RefSeq: NM_007835.2, NM_001198866.1, NM_001198867.1; MGI: 107745

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R1469 (G1)

Quality Score

114

Status

Not validated

Chromosome

Chromosomal Location

83165920-83200117 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 83192889 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 590 (I590N)

Ref Sequence

ENSEMBL: ENSMUSP00000109540 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000077407] [ENSMUST00000113907] [ENSMUST00000113913] [ENSMUST00000113918] [ENSMUST00000113919] [ENSMUST00000130212] [ENSMUST00000141680]

Predicted Effect

probably damaging
Transcript: ENSMUST00000077407
AA Change: I687N

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000076623
Gene: ENSMUSG00000031865
AA Change: I687N

Domain	Start	End	E-Value	Type
CAP_GLY	12	78	5.52e-31	SMART
low complexity region	124	147	N/A	INTRINSIC
low complexity region	148	177	N/A	INTRINSIC
SCOP:d1fxkc_	185	337	3e-3	SMART
low complexity region	363	379	N/A	INTRINSIC
Pfam:Dynactin	489	768	8.2e-91	PFAM
low complexity region	800	820	N/A	INTRINSIC
coiled coil region	914	1009	N/A	INTRINSIC
low complexity region	1025	1043	N/A	INTRINSIC
coiled coil region	1143	1172	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000113907
AA Change: I590N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000109540
Gene: ENSMUSG00000031865
AA Change: I590N

Domain	Start	End	E-Value	Type
low complexity region	5	22	N/A	INTRINSIC
low complexity region	27	50	N/A	INTRINSIC
low complexity region	51	80	N/A	INTRINSIC
low complexity region	93	106	N/A	INTRINSIC
low complexity region	140	158	N/A	INTRINSIC
SCOP:d1lxa__	271	345	8e-3	SMART
Pfam:Dynactin	392	671	7.1e-91	PFAM
low complexity region	703	723	N/A	INTRINSIC
coiled coil region	817	912	N/A	INTRINSIC
low complexity region	928	946	N/A	INTRINSIC
coiled coil region	1046	1075	N/A	INTRINSIC

Predicted Effect

unknown
Transcript: ENSMUST00000113913
AA Change: I707N

SMART Domains

Protein: ENSMUSP00000109546
Gene: ENSMUSG00000031865
AA Change: I707N

Domain	Start	End	E-Value	Type
CAP_GLY	12	78	5.52e-31	SMART
low complexity region	118	139	N/A	INTRINSIC
low complexity region	144	167	N/A	INTRINSIC
low complexity region	168	197	N/A	INTRINSIC
SCOP:d1fxkc_	205	357	3e-3	SMART
low complexity region	383	399	N/A	INTRINSIC
Pfam:Dynactin	509	788	2.5e-90	PFAM
low complexity region	820	840	N/A	INTRINSIC
coiled coil region	934	1029	N/A	INTRINSIC
low complexity region	1051	1069	N/A	INTRINSIC
coiled coil region	1168	1197	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000113918
AA Change: I724N

PolyPhen 2 Score 0.856 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109551
Gene: ENSMUSG00000031865
AA Change: I724N

Domain	Start	End	E-Value	Type
CAP_GLY	29	95	5.52e-31	SMART
low complexity region	135	156	N/A	INTRINSIC
low complexity region	161	184	N/A	INTRINSIC
low complexity region	185	214	N/A	INTRINSIC
low complexity region	227	240	N/A	INTRINSIC
low complexity region	274	292	N/A	INTRINSIC
low complexity region	400	416	N/A	INTRINSIC
Pfam:Dynactin	526	805	3.3e-90	PFAM
low complexity region	837	857	N/A	INTRINSIC
coiled coil region	951	1046	N/A	INTRINSIC
coiled coil region	1147	1176	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000113919
AA Change: I724N

PolyPhen 2 Score 0.856 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109552
Gene: ENSMUSG00000031865
AA Change: I724N

Domain	Start	End	E-Value	Type
CAP_GLY	29	95	5.52e-31	SMART
low complexity region	135	156	N/A	INTRINSIC
low complexity region	161	184	N/A	INTRINSIC
low complexity region	185	214	N/A	INTRINSIC
SCOP:d1fxkc_	222	374	3e-3	SMART
low complexity region	400	416	N/A	INTRINSIC
Pfam:Dynactin	522	805	1.4e-103	PFAM
low complexity region	837	857	N/A	INTRINSIC
coiled coil region	951	1046	N/A	INTRINSIC
low complexity region	1068	1086	N/A	INTRINSIC
coiled coil region	1185	1214	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123313

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127824

Predicted Effect

probably benign
Transcript: ENSMUST00000130212

SMART Domains

Protein: ENSMUSP00000115838
Gene: ENSMUSG00000031865

Domain	Start	End	E-Value	Type
CAP_GLY	12	78	5.52e-31	SMART
low complexity region	124	147	N/A	INTRINSIC
low complexity region	148	177	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130917

Predicted Effect

probably benign
Transcript: ENSMUST00000141680

SMART Domains

Protein: ENSMUSP00000121538
Gene: ENSMUSG00000031865

Domain	Start	End	E-Value	Type
CAP_GLY	12	78	5.52e-31	SMART
low complexity region	118	139	N/A	INTRINSIC
low complexity region	144	159	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153793

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154420

Coding Region Coverage

1x: 98.9%
3x: 95.3%
10x: 69.3%
20x: 30.3%

Validation Efficiency

MGI Phenotype

Strain: 3769512
Lethality: E8-E10
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit interacts with dynein intermediate chain by its domains directly binding to dynein and binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein (CAP-Gly) domain in its N-terminus. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause distal hereditary motor neuronopathy type VIIB (HMN7B) which is also known as distal spinal and bulbar muscular atrophy (dSBMA). [provided by RefSeq, Oct 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit embryonic lethality and developmental arrest at E7.5 associated with increased apoptosis. [provided by MGI curators]

Allele List at MGI

All alleles(20) : Targeted(4) Gene trapped(16)

Other mutations in this stock

Total: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aasdh	A	T	5: 76,891,679	V261E	probably damaging	Het
Abca15	A	G	7: 120,382,497	E1058G	probably benign	Het
Abcb5	T	G	12: 118,867,946	I1224L	possibly damaging	Het
Actn4	A	G	7: 28,905,328	V348A	probably benign	Het
Agtr1b	A	T	3: 20,315,500	L314H	probably damaging	Het
Ankrd55	T	C	13: 112,367,926	M402T	probably benign	Het
Asap2	A	G	12: 21,213,179	Q265R	probably benign	Het
Atp2b4	G	A	1: 133,706,939	R1124C	probably damaging	Het
Atp2c1	A	T	9: 105,435,152	C353*	probably null	Het
Atp8b5	T	A	4: 43,291,733		probably null	Het
Baz1b	T	A	5: 135,217,979	Y761N	probably damaging	Het
Bend6	A	G	1: 33,864,743	V38A	probably benign	Het
Camk1g	T	C	1: 193,362,091	E5G	possibly damaging	Het
Ccdc14	T	A	16: 34,706,782	H352Q	probably damaging	Het
Cdh2	A	G	18: 16,624,267	V641A	possibly damaging	Het
Celsr2	C	A	3: 108,414,108	D463Y	probably damaging	Het
Cfap43	A	G	19: 47,896,875	Y434H	probably damaging	Het
Cnih2	T	C	19: 5,093,702	Y142C	probably damaging	Het
Coa5	T	A	1: 37,420,600	R71*	probably null	Het
Csmd3	A	T	15: 47,669,202	Y2532*	probably null	Het
Cytl1	A	T	5: 37,735,647	M34L	probably benign	Het
Dhx57	T	C	17: 80,254,418	H889R	probably damaging	Het
Dock10	A	G	1: 80,512,558	I1948T	probably benign	Het
Dock3	A	T	9: 106,955,709	N1034K	probably benign	Het
Dzip1l	G	A	9: 99,659,776		probably null	Het
Eif4g1	T	A	16: 20,680,008	V439E	possibly damaging	Het
Eml5	T	C	12: 98,858,823	I712V	probably benign	Het
Epha3	C	T	16: 63,653,494	G300D	probably damaging	Het
Erbb4	A	C	1: 68,560,682	S79A	probably damaging	Het
Fam189a2	G	A	19: 23,973,606	T537I	probably benign	Het
Gclc	T	C	9: 77,781,137	V205A	probably benign	Het
Gdpd4	A	G	7: 97,974,466		probably null	Het
Gm11564	C	T	11: 99,815,232	C124Y	unknown	Het
Gm16494	T	C	17: 47,016,844	E38G	probably damaging	Het
Gtf2h1	T	C	7: 46,805,125		probably null	Het
Gtsf2	G	T	15: 103,441,217	R68S	probably benign	Het
Heatr5b	T	C	17: 78,808,384	Q881R	probably damaging	Het
Hmox1	C	A	8: 75,098,835	L236I	probably benign	Het
Ighv8-12	T	C	12: 115,648,343	I7V	probably benign	Het
Izumo1	T	C	7: 45,623,013	S73P	probably damaging	Het
Kif1bp	A	T	10: 62,559,450	F471Y	probably damaging	Het
Knl1	A	G	2: 119,071,346	N1176S	possibly damaging	Het
Mecom	A	T	3: 29,980,048	L493Q	probably damaging	Het
Mprip	T	C	11: 59,759,190	V1240A	probably damaging	Het
Mrpl3	T	C	9: 105,077,002	S302P	probably damaging	Het
Mycbp2	T	C	14: 103,188,520	T2390A	probably damaging	Het
Myo1c	T	C	11: 75,669,961	S766P	probably damaging	Het
Myo9b	A	G	8: 71,291,036	Q247R	probably damaging	Het
Nav3	G	A	10: 109,760,508	T1423I	probably damaging	Het
Nefh	A	T	11: 4,940,066	I851N	probably benign	Het
Nup98	T	C	7: 102,138,801	T1004A	probably benign	Het
Olfr175-ps1	G	A	16: 58,824,610	T33I	probably benign	Het
Olfr23	T	C	11: 73,940,557	F104L	probably benign	Het
Olfr381	G	A	11: 73,486,323	S167L	possibly damaging	Het
Olfr502	T	C	7: 108,523,204	T249A	probably benign	Het
Osgin1	G	T	8: 119,445,385	R306L	possibly damaging	Het
Otof	A	G	5: 30,380,227	L1246P	probably benign	Het
Pde8a	T	A	7: 81,302,271	N273K	probably damaging	Het
Phf14	T	A	6: 11,933,727	M196K	possibly damaging	Het
Pkd1l3	T	C	8: 109,646,953	S1374P	possibly damaging	Het
Pkhd1l1	T	C	15: 44,536,886	V2142A	probably benign	Het
Plb1	A	G	5: 32,354,826	E1318G	possibly damaging	Het
Plekhh2	A	G	17: 84,575,771	I756V	probably benign	Het
Primpol	A	G	8: 46,593,637	V208A	probably benign	Het
Ptch2	C	A	4: 117,108,465	A389E	probably benign	Het
Pzp	A	G	6: 128,512,356	Y431H	probably benign	Het
Rnf43	G	A	11: 87,731,407	G445R	probably damaging	Het
Scn5a	A	T	9: 119,533,661		probably null	Het
Sfi1	CCTCTC	CCTCTCTC	11: 3,177,419		probably benign	Het
Shisa9	T	A	16: 11,985,071	M164K	probably damaging	Het
Skint1	A	G	4: 112,025,511	I251V	probably benign	Het
Slc16a14	C	T	1: 84,929,461	D31N	probably damaging	Het
Slc22a13	T	C	9: 119,193,295	S548G	possibly damaging	Het
Slc4a9	T	C	18: 36,531,101	F316L	probably benign	Het
Smchd1	C	T	17: 71,349,730	R1914H	probably damaging	Het
Snx16	C	T	3: 10,434,371	D200N	probably damaging	Het
Spock3	A	G	8: 62,951,900	D34G	probably damaging	Het
Sspo	T	C	6: 48,490,982	C4154R	probably damaging	Het
Sytl3	C	T	17: 6,687,324	A131V	probably benign	Het
Tacc1	T	A	8: 25,182,255	D319V	probably benign	Het
Tead1	A	T	7: 112,876,184	K234I	probably damaging	Het
Tgfbrap1	C	T	1: 43,075,458	V161I	probably benign	Het
Tnfaip3	A	G	10: 19,008,269	V121A	probably damaging	Het
Tnnt2	A	G	1: 135,852,055	T297A	possibly damaging	Het
Trappc11	G	A	8: 47,503,965	L809F	probably damaging	Het
Ttn	T	C	2: 76,771,525	I18598V	probably benign	Het
Ugt1a10	G	A	1: 88,216,254	A199T	probably damaging	Het
Unc5a	A	G	13: 54,996,419	N186D	probably damaging	Het
Uqcrfs1	C	A	13: 30,540,801	G252V	probably damaging	Het
Vmn2r115	T	C	17: 23,346,018	I293T	probably damaging	Het
Vmn2r9	T	C	5: 108,843,828	T556A	probably benign	Het
Ythdc2	T	A	18: 44,864,462	Y1029N	probably benign	Het
Zfp451	T	A	1: 33,769,813	K989M	possibly damaging	Het
Zfpm1	C	T	8: 122,335,846	T548M	probably damaging	Het

Other mutations in Dctn1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01113:Dctn1	APN	6	83179897	missense	probably benign	0.00
IGL01450:Dctn1	APN	6	83194110	unclassified	probably benign
IGL01876:Dctn1	APN	6	83197921	missense	probably damaging	1.00
IGL01958:Dctn1	APN	6	83191344	missense	possibly damaging	0.95
IGL02554:Dctn1	APN	6	83182722	missense	probably damaging	1.00
IGL02668:Dctn1	APN	6	83191048	missense	possibly damaging	0.89
IGL02814:Dctn1	APN	6	83189914	missense	probably damaging	1.00
IGL02818:Dctn1	APN	6	83192514	missense	possibly damaging	0.86
IGL03007:Dctn1	APN	6	83182708	missense	probably damaging	1.00
IGL03065:Dctn1	APN	6	83192493	missense	probably damaging	0.99
IGL03083:Dctn1	APN	6	83197484	splice site	probably benign
IGL03394:Dctn1	APN	6	83191284	missense	possibly damaging	0.61
E0374:Dctn1	UTSW	6	83194174	missense	possibly damaging	0.93
IGL03014:Dctn1	UTSW	6	83197369	intron	probably benign
PIT4812001:Dctn1	UTSW	6	83199762	missense	possibly damaging	0.86
R0044:Dctn1	UTSW	6	83191134	missense	probably damaging	1.00
R0047:Dctn1	UTSW	6	83182632	nonsense	probably null
R0047:Dctn1	UTSW	6	83182632	nonsense	probably null
R0057:Dctn1	UTSW	6	83179892	missense	probably benign	0.14
R0731:Dctn1	UTSW	6	83183089	missense	probably damaging	0.98
R0738:Dctn1	UTSW	6	83190107	critical splice donor site	probably null
R0755:Dctn1	UTSW	6	83189077	missense	probably damaging	0.96
R0839:Dctn1	UTSW	6	83190477	missense	possibly damaging	0.53
R1035:Dctn1	UTSW	6	83190220	missense	probably damaging	1.00
R1454:Dctn1	UTSW	6	83197508	missense	possibly damaging	0.93
R1469:Dctn1	UTSW	6	83192889	missense	probably damaging	1.00
R1627:Dctn1	UTSW	6	83195082	missense	probably damaging	0.99
R1631:Dctn1	UTSW	6	83197596	missense	possibly damaging	0.56
R1812:Dctn1	UTSW	6	83192518	missense	possibly damaging	0.85
R1928:Dctn1	UTSW	6	83199184	splice site	probably benign
R2008:Dctn1	UTSW	6	83189956	missense	probably damaging	0.99
R2242:Dctn1	UTSW	6	83199705	missense	probably damaging	0.99
R2259:Dctn1	UTSW	6	83197586	missense	possibly damaging	0.46
R2422:Dctn1	UTSW	6	83199800	missense	possibly damaging	0.92
R2483:Dctn1	UTSW	6	83194187	missense	probably damaging	1.00
R4455:Dctn1	UTSW	6	83195049	missense	probably damaging	1.00
R4724:Dctn1	UTSW	6	83189938	missense	possibly damaging	0.53
R4812:Dctn1	UTSW	6	83189937	missense	probably benign	0.24
R4819:Dctn1	UTSW	6	83190519	missense	probably damaging	0.97
R4831:Dctn1	UTSW	6	83199771	missense	possibly damaging	0.46
R4928:Dctn1	UTSW	6	83189207	missense	possibly damaging	0.73
R5087:Dctn1	UTSW	6	83191639	missense	probably damaging	1.00
R5354:Dctn1	UTSW	6	83183126	missense	possibly damaging	0.93
R5372:Dctn1	UTSW	6	83190210	missense	probably damaging	0.96
R5493:Dctn1	UTSW	6	83182564	missense	possibly damaging	0.89
R5494:Dctn1	UTSW	6	83182564	missense	possibly damaging	0.89
R5732:Dctn1	UTSW	6	83197949	critical splice donor site	probably null
R5856:Dctn1	UTSW	6	83197865	missense	probably damaging	1.00
R6025:Dctn1	UTSW	6	83193691	splice site	probably null
R6999:Dctn1	UTSW	6	83191281	missense	possibly damaging	0.89
R7052:Dctn1	UTSW	6	83195280	splice site	probably null
R7133:Dctn1	UTSW	6	83180044	splice site	probably null
R7485:Dctn1	UTSW	6	83189905	missense	possibly damaging	0.85
R7607:Dctn1	UTSW	6	83195069	nonsense	probably null
R7729:Dctn1	UTSW	6	83183060	missense	probably damaging	1.00
R7749:Dctn1	UTSW	6	83186141	intron	probably benign
R8282:Dctn1	UTSW	6	83199756	missense	possibly damaging	0.91

Predicted Primers

Posted On

2017-12-01