Incidental Mutation 'R7100:Lmna'
ID 550751
Institutional Source Beutler Lab
Gene Symbol Lmna
Ensembl Gene ENSMUSG00000028063
Gene Name lamin A
Synonyms lamin A/C, Dhe
MMRRC Submission 045192-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7100 (G1)
Quality Score 225.009
Status Validated
Chromosome 3
Chromosomal Location 88388455-88413842 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 88392297 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 365 (I365T)
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: I365T

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000029699
Gene: ENSMUSG00000028063
AA Change: I365T

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000036252
AA Change: I253T

PolyPhen 2 Score 0.952 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000040265
Gene: ENSMUSG00000028063
AA Change: I253T

DomainStartEndE-ValueType
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: I365T

PolyPhen 2 Score 0.432 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000113093
Gene: ENSMUSG00000028063
AA Change: I365T

DomainStartEndE-ValueType
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
Meta Mutation Damage Score 0.6454 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 98% (54/55)
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: 57 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Actl10 A G 2: 154,394,315 (GRCm39) E89G probably damaging Het
Adgrv1 A T 13: 81,419,016 (GRCm39) V5993E probably damaging Het
Amdhd1 T C 10: 93,372,936 (GRCm39) probably null Het
Amph T C 13: 19,334,011 (GRCm39) *691Q probably null Het
Ankrd55 A G 13: 112,492,644 (GRCm39) K272E probably benign Het
Arhgef10l C T 4: 140,244,126 (GRCm39) V838I possibly damaging Het
Arl2 C A 19: 6,184,774 (GRCm39) V160F probably benign Het
Catsperb T C 12: 101,412,297 (GRCm39) V128A possibly damaging Het
Cdk11b T A 4: 155,710,050 (GRCm39) L17H probably damaging Het
Cpsf1 A T 15: 76,480,314 (GRCm39) N1391K possibly damaging Het
Cpxm2 C T 7: 131,656,544 (GRCm39) A573T probably benign Het
Cspg4b T A 13: 113,455,501 (GRCm39) F516I Het
Daxx T C 17: 34,130,416 (GRCm39) S144P probably damaging Het
Dpp3 T C 19: 4,968,069 (GRCm39) D303G probably damaging Het
Fam181a T A 12: 103,282,132 (GRCm39) N12K probably damaging Het
Flg2 A T 3: 93,111,018 (GRCm39) R1015S unknown Het
Fstl5 A G 3: 76,443,600 (GRCm39) H315R probably benign Het
Fut4 A G 9: 14,662,689 (GRCm39) S202P probably damaging Het
Gm5114 T C 7: 39,057,708 (GRCm39) D637G possibly damaging Het
Gstcd G T 3: 132,790,704 (GRCm39) T21K probably benign Het
Heca C T 10: 17,791,121 (GRCm39) V312M probably benign Het
Herpud1 A G 8: 95,117,475 (GRCm39) R144G probably damaging Het
Hycc2 T A 1: 58,573,653 (GRCm39) T384S possibly damaging Het
Ino80 A G 2: 119,204,994 (GRCm39) S1511P possibly damaging Het
Irf2bp2 T C 8: 127,318,472 (GRCm39) T365A probably benign Het
Klk1 G A 7: 43,878,848 (GRCm39) G214E probably damaging Het
Lama3 A T 18: 12,715,701 (GRCm39) N1719I possibly damaging Het
Lrp8 C A 4: 107,659,647 (GRCm39) A13E possibly damaging Het
Ly75 A G 2: 60,136,778 (GRCm39) L1483P probably benign Het
Maco1 T C 4: 134,533,971 (GRCm39) D550G probably damaging Het
Mid1 A G X: 168,768,073 (GRCm39) D407G probably benign Het
Mpl G T 4: 118,314,607 (GRCm39) A21E Het
Mus81 C T 19: 5,534,239 (GRCm39) G360S probably damaging Het
Nmt2 T A 2: 3,313,950 (GRCm39) S250T probably benign Het
Nr1d1 C A 11: 98,662,160 (GRCm39) R158L probably damaging Het
Pcgf6 G A 19: 47,039,153 (GRCm39) P36S unknown Het
Pcnx2 G A 8: 126,485,853 (GRCm39) A1915V probably benign Het
Peak1 A G 9: 56,166,677 (GRCm39) V417A probably damaging Het
Phf20l1 A G 15: 66,476,689 (GRCm39) N262S probably benign Het
Plaat5 T A 19: 7,616,923 (GRCm39) F313I unknown Het
Ppp2r5d A G 17: 46,996,608 (GRCm39) V355A probably benign Het
Rasa3 T C 8: 13,636,897 (GRCm39) T395A probably benign Het
Rims1 T A 1: 22,416,697 (GRCm39) I432F probably benign Het
Rnf123 C T 9: 107,933,838 (GRCm39) C1080Y probably damaging Het
Serpina3g T C 12: 104,204,570 (GRCm39) probably benign Het
Shank2 T A 7: 143,964,901 (GRCm39) D836E possibly damaging Het
Slc24a5 A C 2: 124,922,591 (GRCm39) S118R probably damaging Het
Smg1 G T 7: 117,783,743 (GRCm39) H1048N unknown Het
Specc1l T G 10: 75,081,329 (GRCm39) S242A probably benign Het
Tagap1 A T 17: 7,224,111 (GRCm39) L195Q possibly damaging Het
Trpc3 C A 3: 36,704,216 (GRCm39) E580D probably benign Het
Ttn A T 2: 76,541,166 (GRCm39) V33940E probably benign Het
Upp2 G T 2: 58,681,817 (GRCm39) R318L probably benign Het
Vezt T A 10: 93,832,795 (GRCm39) E205D probably benign Het
Vmn1r177 A G 7: 23,565,535 (GRCm39) F114L probably benign Het
Vmn2r53 C A 7: 12,315,513 (GRCm39) E769* probably null Het
Vnn3 T C 10: 23,741,840 (GRCm39) Y382H probably damaging Het
Other mutations in Lmna
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R9347:Lmna UTSW 3 88,393,548 (GRCm39) missense probably damaging 0.98
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'- TCTCGGAAGACTCCAGCTTG -3'
(R):5'- GGAGCTCATCAGACCCTTTG -3'

Sequencing Primer
(F):5'- TCCACCCTGAGACTGGGATGAG -3'
(R):5'- GTCTTCCCCGCCCCAGTTG -3'
Posted On 2019-05-15