Mutagenetix > Incidental Mutations

Incidental Mutation 'R4751:Lmna'

357562

Institutional Source

Beutler Lab

Gene Symbol

Lmna

Ensembl Gene

ENSMUSG00000028063

Gene Name

lamin A

Synonyms

Dhe, lamin A/C

MMRRC Submission

041970-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4751 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

88480147-88509956 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 88486533 bp

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 246 (Q246R)

Ref Sequence

ENSEMBL: ENSMUSP00000113093 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029699] [ENSMUST00000036252] [ENSMUST00000120377]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000029699
AA Change: Q246R

PolyPhen 2 Score 0.869 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000029699
Gene: ENSMUSG00000028063
AA Change: Q246R

Domain	Start	End	E-Value	Type
Filament	30	386	4.38e-45	SMART
low complexity region	395	414	N/A	INTRINSIC
low complexity region	422	431	N/A	INTRINSIC
Pfam:LTD	433	544	4e-15	PFAM
low complexity region	551	562	N/A	INTRINSIC
low complexity region	565	576	N/A	INTRINSIC
low complexity region	600	639	N/A	INTRINSIC
low complexity region	651	663	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000036252
AA Change: Q134R

PolyPhen 2 Score 0.043 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000040265
Gene: ENSMUSG00000028063
AA Change: Q134R

Domain	Start	End	E-Value	Type
Pfam:Filament	2	274	5.6e-66	PFAM
low complexity region	283	302	N/A	INTRINSIC
Pfam:LTD	317	436	1.2e-22	PFAM
low complexity region	439	450	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000120377
AA Change: Q246R

PolyPhen 2 Score 0.869 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000113093
Gene: ENSMUSG00000028063
AA Change: Q246R

Domain	Start	End	E-Value	Type
Pfam:Filament	30	386	1.3e-95	PFAM
low complexity region	395	414	N/A	INTRINSIC
Pfam:LTD	429	548	1.7e-22	PFAM
low complexity region	551	562	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135494

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147537

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150496

Meta Mutation Damage Score

0.076

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.4%

Validation Efficiency

95% (124/131)

MGI Phenotype

FUNCTION: This gene encodes a protein that is a member of the lamin family. Nuclear lamins, intermediate filament-like proteins, are the major components of the nuclear lamina, a protein meshwork associated with the inner nuclear membrane. This meshwork is thought to maintain the integrity of the nuclear envelope, participate in chromatin organization, and regulate gene transcription. Vertebrate lamins consist of two types, A and B. This protein is an A-type and is proposed to be developmentally regulated. In mouse deficiency of this gene is associated with muscular dystrophy. Mouse lines with different mutations in this gene serve as pathophysiological models for several human laminopathies. In humans, mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, May 2013]
PHENOTYPE: Homozygotes for targeted mutations exhibit retarded postnatal growth, muscular dystrophy, reduced fat stores, micrognathy, abnormal dentition, impaired gonadal development, malformed scapulae, hyperkeratosis, and die by 8 weeks of age. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 115 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9130023H24Rik	A	T	7: 128,237,086	C112S	probably benign	Het
Abca13	G	A	11: 9,277,973		probably null	Het
Abca14	A	G	7: 120,312,177	E1328G	probably benign	Het
Abca9	T	A	11: 110,130,570	I1105F	probably benign	Het
Abr	T	C	11: 76,456,608	N396D	possibly damaging	Het
Aftph	A	C	11: 20,727,074	C178W	probably damaging	Het
Akr1c14	T	C	13: 4,065,338	F89S	possibly damaging	Het
Ank3	C	T	10: 69,986,206	A1518V	probably benign	Het
Arfgap2	T	G	2: 91,267,368	S143R	probably benign	Het
Aspdh	T	A	7: 44,467,205	C107*	probably null	Het
Asphd2	C	A	5: 112,391,746	G74W	probably damaging	Het
AU040320	G	A	4: 126,854,466		probably null	Het
B3glct	T	A	5: 149,725,402		probably null	Het
Bcl9l	A	G	9: 44,506,803	K646R	probably damaging	Het
Brat1	T	G	5: 140,718,296	L768R	probably damaging	Het
Btbd18	T	A	2: 84,667,921	Y634*	probably null	Het
Bub1	T	A	2: 127,823,938		probably benign	Het
Carns1	A	T	19: 4,166,418	D588E	probably damaging	Het
Cast	T	C	13: 74,746,047	K141E	probably damaging	Het
Cd109	CATTTATTTATTTATTTATTTATTTATTTATTTAT	CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT	9: 78,712,500		probably benign	Het
Chsy3	T	C	18: 59,175,800	S42P	possibly damaging	Het
Clca1	A	T	3: 145,004,848	F865I	possibly damaging	Het
Clec4f	T	A	6: 83,645,282	M526L	possibly damaging	Het
Clnk	T	C	5: 38,720,913	E301G	probably benign	Het
Colgalt2	T	A	1: 152,489,876	I309N	probably benign	Het
Cyp2e1	A	T	7: 140,774,716	K326*	probably null	Het
Dagla	T	A	19: 10,250,394	T717S	probably benign	Het
Dnajc11	G	A	4: 151,968,542	R141H	probably benign	Het
Dst	A	G	1: 34,191,884	K2853E	probably benign	Het
Eif4g1	A	G	16: 20,686,515	K1208E	possibly damaging	Het
Elane	A	G	10: 79,886,791	R48G	probably benign	Het
Fbxo30	T	A	10: 11,290,195	N220K	probably benign	Het
Fbxo33	A	T	12: 59,200,928		probably benign	Het
Fetub	G	A	16: 22,937,895	V169I	probably benign	Het
Gm13762	A	G	2: 88,973,133	C253R	probably damaging	Het
Gm5861	T	A	5: 11,186,491	Y138N	probably damaging	Het
Gpx6	A	C	13: 21,317,064	Q107H	probably damaging	Het
Hist2h2bb	A	T	3: 96,269,151		probably benign	Het
Homer3	A	T	8: 70,285,434	I19F	probably damaging	Het
Hspa4	C	T	11: 53,284,199	V144I	probably benign	Het
Icos	C	T	1: 60,993,717	S25L	probably benign	Het
Ifna4	A	G	4: 88,841,948	T30A	probably benign	Het
Ino80b	C	T	6: 83,124,750	G46D	probably damaging	Het
Kpna2	T	G	11: 106,992,664	I100L	possibly damaging	Het
Krt71	C	T	15: 101,735,466	G446R	probably damaging	Het
Krtap31-2	A	G	11: 99,936,576	N78S	possibly damaging	Het
Lman1	A	G	18: 65,998,434	S132P	probably benign	Het
Lrp10	T	A	14: 54,468,592	V413E	probably damaging	Het
Macf1	A	C	4: 123,471,650	I1541S	probably benign	Het
Med24	A	G	11: 98,706,432	L874P	probably damaging	Het
Mgll	T	A	6: 88,725,111		probably benign	Het
Mrpl37	A	T	4: 107,057,475	L364Q	probably damaging	Het
Mrpl47	C	T	3: 32,728,441	R209H	probably benign	Het
Muc5ac	T	C	7: 141,817,601	F3285L	probably benign	Het
Mylk	A	G	16: 34,879,169	R301G	probably benign	Het
Nacad	A	G	11: 6,605,726	L8P	unknown	Het
Ncf1	T	A	5: 134,229,545	H8L	probably damaging	Het
Ncoa3	T	A	2: 166,069,903	M1383K	possibly damaging	Het
Necab2	C	T	8: 119,467,598	S271L	probably benign	Het
Nme8	A	T	13: 19,675,638		probably null	Het
Nsrp1	T	G	11: 77,076,719	T16P	possibly damaging	Het
Obox3	A	T	7: 15,625,692		probably null	Het
Olfr1211	T	A	2: 88,929,914	I134F	probably damaging	Het
Olfr1416	C	A	1: 92,479,983	A213S	probably benign	Het
Olfr1428	T	A	19: 12,109,177	Y123F	probably damaging	Het
Olfr355	T	C	2: 36,927,583	H177R	probably damaging	Het
Olfr667	A	T	7: 104,916,410	Y295*	probably null	Het
Osbpl3	C	G	6: 50,300,997	E790Q	possibly damaging	Het
Osmr	A	T	15: 6,842,852	W254R	probably damaging	Het
Otoa	T	C	7: 121,132,924		probably benign	Het
Pagr1a	A	T	7: 127,015,379	L218H	probably damaging	Het
Pcdha11	G	A	18: 37,006,944	G542D	probably damaging	Het
Pck2	T	A	14: 55,542,561	I54N	probably damaging	Het
Ppif	T	C	14: 25,699,499	V173A	probably damaging	Het
Ptgs2	T	A	1: 150,104,020	L292H	probably damaging	Het
Ptpru	A	G	4: 131,802,586	S604P	probably damaging	Het
Qrfpr	T	C	3: 36,182,622	H210R	possibly damaging	Het
Rasgrf1	A	G	9: 89,910,118	T41A	probably damaging	Het
Rasgrf1	A	G	9: 90,012,866	H1113R	probably damaging	Het
Rhoc	T	A	3: 104,792,647	I80N	probably damaging	Het
Riok3	A	G	18: 12,153,983	N472S	probably benign	Het
Rnf213	A	G	11: 119,445,745	Y3314C	probably benign	Het
Shank2	C	T	7: 144,409,468	T264I	probably damaging	Het
Shroom3	G	T	5: 92,943,086	V1151F	probably damaging	Het
Sipa1l1	A	G	12: 82,341,194	I65V	probably benign	Het
Slc22a19	T	C	19: 7,691,145	K291R	possibly damaging	Het
Slc22a20	T	C	19: 5,980,460	I315V	probably benign	Het
Slc44a1	A	T	4: 53,560,973	D563V	probably damaging	Het
Smchd1	A	T	17: 71,391,468	H1104Q	probably benign	Het
Spcs2	A	T	7: 99,844,769		probably null	Het
Sptb	T	C	12: 76,627,110	E301G	probably benign	Het
Stum	T	C	1: 180,442,669	D86G	probably damaging	Het
Sufu	A	T	19: 46,483,649	D449V	probably benign	Het
Sun5	T	C	2: 153,866,016		probably null	Het
Tbc1d15	T	A	10: 115,202,587	I574F	probably damaging	Het
Tert	G	A	13: 73,628,063	S311N	possibly damaging	Het
Tiparp	T	C	3: 65,552,804	Y507H	probably damaging	Het
Tnk2	T	C	16: 32,679,857	C158R	probably damaging	Het
Tpgs1	T	C	10: 79,675,620	S199P	possibly damaging	Het
Trdmt1	G	T	2: 13,544,653		probably benign	Het
Trp53bp1	T	A	2: 121,227,809	D944V	probably damaging	Het
Tsc1	T	A	2: 28,679,081	I720N	probably damaging	Het
Ttn	T	C	2: 76,709,605	T34346A	probably benign	Het
Ttn	T	C	2: 76,897,581		probably benign	Het
Uba7	T	A	9: 107,979,805	C686S	possibly damaging	Het
Ush2a	T	A	1: 188,850,087	F3782L	probably damaging	Het
Vars2	A	T	17: 35,659,343	H745Q	possibly damaging	Het
Vgf	T	A	5: 137,032,401	D472E	probably damaging	Het
Vmn2r15	T	C	5: 109,286,754	M695V	probably benign	Het
Vps41	A	T	13: 18,811,622	D208V	probably damaging	Het
Vta1	C	T	10: 14,655,816	A272T	probably benign	Het
Wnk4	G	A	11: 101,276,362		probably benign	Het
Zfp507	T	C	7: 35,794,382	K412R	probably damaging	Het
Zfp768	A	G	7: 127,344,762	F65L	possibly damaging	Het
Zfp956	T	C	6: 47,963,576	S290P	probably benign	Het

Other mutations in Lmna

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00468:Lmna	APN	3	88484684	missense	probably benign	0.05
IGL00933:Lmna	APN	3	88482549	missense	possibly damaging	0.73
IGL01347:Lmna	APN	3	88484963	missense	probably benign	0.42
IGL02881:Lmna	APN	3	88502926	missense	possibly damaging	0.56
P0029:Lmna	UTSW	3	88483917	missense	possibly damaging	0.88
R0606:Lmna	UTSW	3	88482578	missense	probably damaging	1.00
R1547:Lmna	UTSW	3	88482351	missense	probably benign	0.00
R5157:Lmna	UTSW	3	88484107	missense	probably damaging	1.00
R5857:Lmna	UTSW	3	88482531	unclassified	probably benign
R6112:Lmna	UTSW	3	88486621	nonsense	probably null
R6263:Lmna	UTSW	3	88502958	missense	probably damaging	1.00
R6328:Lmna	UTSW	3	88486506	missense	probably damaging	1.00
R6604:Lmna	UTSW	3	88488282	missense	probably damaging	0.97
R7100:Lmna	UTSW	3	88484990	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- CAGACTGCCTGGCATTATCC -3'
(R):5'- GGAGTTACGACTTCTGGTCTCAG -3'

Sequencing Primer
(F):5'- TGGCATTATCCAGCTGCAG -3'
(R):5'- GCTTCTAAGGAACCATTGCG -3'

Posted On

2015-11-11