Mutagenetix > Incidental Mutation

Incidental Mutation 'R9347:Lmna'

707834

Institutional Source

Beutler Lab

Gene Symbol

Lmna

Ensembl Gene

ENSMUSG00000028063

Gene Name

lamin A

Synonyms

lamin A/C, Dhe

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9347 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

88388455-88413842 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 88393548 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 300 (D300G)

Ref Sequence

ENSEMBL: ENSMUSP00000029699 (fasta)

Gene Model

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

AlphaFold

P48678

PDB Structure

Solution structure of immunoglobulin like domain of mouse nuclear lamin [SOLUTION NMR]

Predicted Effect

probably damaging
Transcript: ENSMUST00000029699
AA Change: D300G

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000029699
Gene: ENSMUSG00000028063
AA Change: D300G

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: D188G

PolyPhen 2 Score 0.104 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000040265
Gene: ENSMUSG00000028063
AA Change: D188G

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

probably benign
Transcript: ENSMUST00000120377
AA Change: D300G

PolyPhen 2 Score 0.115 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000113093
Gene: ENSMUSG00000028063
AA Change: D300G

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca17	A	T	17: 24,483,479 (GRCm39)	M1659K	probably benign	Het
Ace	C	A	11: 105,864,958 (GRCm39)	Q544K	probably damaging	Het
Agpat4	A	G	17: 12,429,168 (GRCm39)	E140G	possibly damaging	Het
Akap12	A	G	10: 4,303,640 (GRCm39)	D150G	probably benign	Het
Akap6	A	G	12: 53,115,894 (GRCm39)	Y999C	probably damaging	Het
Ank1	A	G	8: 23,607,076 (GRCm39)	I1326V	possibly damaging	Het
Apold1	T	A	6: 134,960,999 (GRCm39)	L151Q	probably damaging	Het
Bmal1	A	G	7: 112,898,487 (GRCm39)	D305G	possibly damaging	Het
Brsk2	A	G	7: 141,552,133 (GRCm39)	S564G	probably damaging	Het
Ceacam18	T	C	7: 43,294,915 (GRCm39)	V325A	possibly damaging	Het
Clstn2	T	C	9: 97,464,654 (GRCm39)	Y167C	probably damaging	Het
Cyp11a1	G	T	9: 57,928,141 (GRCm39)	V324L	possibly damaging	Het
Ddx27	A	G	2: 166,861,950 (GRCm39)	T151A	possibly damaging	Het
Dhrs4	A	G	14: 55,727,306 (GRCm39)	I252M	possibly damaging	Het
Dlg2	A	G	7: 91,360,900 (GRCm39)	D6G	probably benign	Het
Dnah8	G	A	17: 30,927,333 (GRCm39)	E1330K	probably benign	Het
Ehd3	A	G	17: 74,137,391 (GRCm39)	E520G	probably benign	Het
Epha5	A	G	5: 84,479,731 (GRCm39)	V91A	possibly damaging	Het
Fam20c	C	A	5: 138,743,676 (GRCm39)	H237Q	probably benign	Het
Fam217a	C	T	13: 35,094,662 (GRCm39)	G366S	probably damaging	Het
Fancf	T	C	7: 51,511,359 (GRCm39)	E215G	probably benign	Het
Fermt3	A	T	19: 6,980,664 (GRCm39)	I301N	probably damaging	Het
Fyco1	A	T	9: 123,660,350 (GRCm39)		probably null	Het
Gen1	T	C	12: 11,311,068 (GRCm39)	N55D	probably damaging	Het
Gm20604	A	T	12: 102,709,636 (GRCm39)	C75S	unknown	Het
Gm3045	T	A	13: 56,578,160 (GRCm39)	V199D	unknown	Het
Gm49368	A	G	7: 127,712,178 (GRCm39)	T805A	possibly damaging	Het
Hgf	T	C	5: 16,809,921 (GRCm39)		probably null	Het
Hnrnpul2	T	A	19: 8,798,080 (GRCm39)	H145Q	probably benign	Het
Ift140	A	G	17: 25,313,753 (GRCm39)	M1395V	probably benign	Het
Il17rc	T	G	6: 113,457,780 (GRCm39)		probably null	Het
Kansl1l	T	A	1: 66,840,347 (GRCm39)	T318S	probably benign	Het
Kcnc1	A	T	7: 46,077,034 (GRCm39)	N279Y	probably damaging	Het
Khdrbs2	T	A	1: 32,511,828 (GRCm39)	H264Q	probably benign	Het
Klf12	A	G	14: 100,260,144 (GRCm39)	V195A	possibly damaging	Het
Lhfpl2	A	G	13: 94,328,539 (GRCm39)	E200G	probably damaging	Het
Lrif1	A	G	3: 106,641,674 (GRCm39)	T17A	possibly damaging	Het
Mdm1	A	G	10: 117,982,523 (GRCm39)	I53V	probably damaging	Het
Mga	T	A	2: 119,733,518 (GRCm39)	I122N	probably damaging	Het
Mos	A	G	4: 3,871,763 (GRCm39)	S18P	probably benign	Het
Mterf3	C	T	13: 67,062,852 (GRCm39)	V295I	possibly damaging	Het
Muc16	G	A	9: 18,571,511 (GRCm39)	T336I	unknown	Het
Myo15a	T	C	11: 60,374,555 (GRCm39)	S136P		Het
Nav3	T	A	10: 109,738,955 (GRCm39)	I128F	probably damaging	Het
Nphs1	A	G	7: 30,170,594 (GRCm39)	D928G	probably damaging	Het
Or52z15	A	G	7: 103,332,464 (GRCm39)	I180V	probably damaging	Het
Or5b114-ps1	A	T	19: 13,352,553 (GRCm39)	T76S	possibly damaging	Het
Or5m13b	T	A	2: 85,753,819 (GRCm39)	V69E	probably damaging	Het
Or5p70	A	G	7: 107,995,259 (GRCm39)	K311E	probably benign	Het
Or8u10	T	C	2: 85,915,911 (GRCm39)	D70G	possibly damaging	Het
Parvb	T	C	15: 84,155,523 (GRCm39)		probably null	Het
Patj	A	C	4: 98,576,484 (GRCm39)	E574A	probably benign	Het
Ppp2r1a	A	G	17: 21,181,877 (GRCm39)	N465S	probably benign	Het
Pramel34	T	A	5: 93,786,697 (GRCm39)	E24V	probably damaging	Het
Senp6	A	G	9: 80,046,379 (GRCm39)	K950E	possibly damaging	Het
Septin12	T	C	16: 4,805,481 (GRCm39)	H304R	probably damaging	Het
Septin3	T	C	15: 82,167,914 (GRCm39)	V110A	probably damaging	Het
Slc25a35	G	T	11: 68,862,076 (GRCm39)	V170L	probably benign	Het
Slco3a1	A	T	7: 73,934,153 (GRCm39)	L673Q	possibly damaging	Het
Smim35	A	G	9: 45,154,271 (GRCm39)	N44S	possibly damaging	Het
Tcp1	A	G	17: 13,136,687 (GRCm39)	M23V	probably benign	Het
Thg1l	T	C	11: 45,845,288 (GRCm39)		probably benign	Het
Tiam2	G	A	17: 3,471,923 (GRCm39)	E522K	probably benign	Het
Tie1	G	A	4: 118,341,867 (GRCm39)	T194I	possibly damaging	Het
Vmn2r49	T	A	7: 9,718,674 (GRCm39)	E463D	probably benign	Het
Wdr1	C	A	5: 38,697,355 (GRCm39)		probably null	Het
Zbtb38	A	T	9: 96,567,649 (GRCm39)	M1145K	probably damaging	Het

Other mutations in Lmna

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00468:Lmna	APN	3	88,391,991 (GRCm39)	missense	probably benign	0.05
IGL00933:Lmna	APN	3	88,389,856 (GRCm39)	missense	possibly damaging	0.73
IGL01347:Lmna	APN	3	88,392,270 (GRCm39)	missense	probably benign	0.42
IGL02881:Lmna	APN	3	88,410,233 (GRCm39)	missense	possibly damaging	0.56
P0029:Lmna	UTSW	3	88,391,224 (GRCm39)	missense	possibly damaging	0.88
R0606:Lmna	UTSW	3	88,389,885 (GRCm39)	missense	probably damaging	1.00
R1547:Lmna	UTSW	3	88,389,658 (GRCm39)	missense	probably benign	0.00
R4751:Lmna	UTSW	3	88,393,840 (GRCm39)	missense	possibly damaging	0.87
R5157:Lmna	UTSW	3	88,391,414 (GRCm39)	missense	probably damaging	1.00
R5857:Lmna	UTSW	3	88,389,838 (GRCm39)	unclassified	probably benign
R6112:Lmna	UTSW	3	88,393,928 (GRCm39)	nonsense	probably null
R6263:Lmna	UTSW	3	88,410,265 (GRCm39)	missense	probably damaging	1.00
R6328:Lmna	UTSW	3	88,393,813 (GRCm39)	missense	probably damaging	1.00
R6604:Lmna	UTSW	3	88,395,589 (GRCm39)	missense	probably damaging	0.97
R7100:Lmna	UTSW	3	88,392,297 (GRCm39)	missense	probably damaging	0.99
R8080:Lmna	UTSW	3	88,393,868 (GRCm39)	missense	probably damaging	0.99
R8841:Lmna	UTSW	3	88,391,920 (GRCm39)	critical splice donor site	probably null
R9665:Lmna	UTSW	3	88,389,793 (GRCm39)	missense	probably benign	0.18
R9666:Lmna	UTSW	3	88,389,857 (GRCm39)	frame shift	probably null
R9667:Lmna	UTSW	3	88,389,857 (GRCm39)	frame shift	probably null
R9694:Lmna	UTSW	3	88,389,857 (GRCm39)	frame shift	probably null
RF013:Lmna	UTSW	3	88,391,361 (GRCm39)	missense	probably benign	0.00
Z1177:Lmna	UTSW	3	88,393,543 (GRCm39)	missense	probably benign	0.17

Predicted Primers

PCR Primer
(F):5'- TCTGAGGATCAGGGCTAGCTAAAG -3'
(R):5'- AAGACATACTCCGCCAAGGTG -3'

Sequencing Primer
(F):5'- GCTAGCTAAAGGAGAGCCC -3'
(R):5'- AAGGTGCTGGCCTCATCCTG -3'

Posted On

2022-04-18