Incidental Mutation 'P0007:Lgi3'
ID 7587
Institutional Source Beutler Lab
Gene Symbol Lgi3
Ensembl Gene ENSMUSG00000033595
Gene Name leucine-rich repeat LGI family, member 3
Synonyms
MMRRC Submission 038263-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.061) question?
Stock # P0007 (G1)
Quality Score
Status Validated
Chromosome 14
Chromosomal Location 70768125-70775764 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 70774152 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 442 (Y442C)
Ref Sequence ENSEMBL: ENSMUSP00000046705 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000047331] [ENSMUST00000226548]
AlphaFold Q8K406
Predicted Effect probably damaging
Transcript: ENSMUST00000047331
AA Change: Y442C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000046705
Gene: ENSMUSG00000033595
AA Change: Y442C

DomainStartEndE-ValueType
signal peptide 1 30 N/A INTRINSIC
low complexity region 31 47 N/A INTRINSIC
LRR 87 110 2.63e0 SMART
LRR 111 134 1.07e0 SMART
LRR_TYP 135 158 2.84e-5 SMART
LRRCT 170 219 2.76e-4 SMART
Pfam:EPTP 222 263 7.6e-13 PFAM
Pfam:EPTP 268 309 1.3e-12 PFAM
Pfam:EPTP 314 360 1.1e-14 PFAM
Pfam:EPTP 363 405 2.4e-9 PFAM
Pfam:EPTP 410 452 1.2e-11 PFAM
Pfam:EPTP 455 496 2.2e-12 PFAM
Pfam:EPTP 501 541 2.4e-7 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226376
Predicted Effect probably benign
Transcript: ENSMUST00000226548
Meta Mutation Damage Score 0.5930 question?
Coding Region Coverage
  • 1x: 85.2%
  • 3x: 80.2%
  • 10x: 65.3%
  • 20x: 42.8%
Validation Efficiency 94% (102/109)
Allele List at MGI

All alleles(2) : Targeted(2)
Other mutations in this stock
Total: 8 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamts6 A G 13: 104,433,999 (GRCm39) T143A possibly damaging Het
Cfap74 T A 4: 155,506,685 (GRCm39) S139T possibly damaging Het
Fbxo7 T C 10: 85,869,157 (GRCm39) S204P possibly damaging Het
Itga2 A T 13: 115,002,735 (GRCm39) I585N probably damaging Het
Magi1 A G 6: 93,722,969 (GRCm39) I530T probably damaging Het
Med12l T C 3: 58,998,816 (GRCm39) probably benign Het
Nbeal1 A G 1: 60,358,847 (GRCm39) I1176M probably damaging Het
Ostn G T 16: 27,143,279 (GRCm39) G36* probably null Het
Other mutations in Lgi3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01639:Lgi3 APN 14 70,770,825 (GRCm39) missense probably benign 0.05
IGL02203:Lgi3 APN 14 70,771,958 (GRCm39) missense possibly damaging 0.68
R0114:Lgi3 UTSW 14 70,768,469 (GRCm39) start gained probably benign
R0225:Lgi3 UTSW 14 70,770,261 (GRCm39) missense probably benign
R0242:Lgi3 UTSW 14 70,772,255 (GRCm39) nonsense probably null
R0242:Lgi3 UTSW 14 70,772,255 (GRCm39) nonsense probably null
R0244:Lgi3 UTSW 14 70,772,138 (GRCm39) missense probably benign 0.30
R0396:Lgi3 UTSW 14 70,772,280 (GRCm39) missense probably damaging 1.00
R0479:Lgi3 UTSW 14 70,771,992 (GRCm39) unclassified probably benign
R1652:Lgi3 UTSW 14 70,768,656 (GRCm39) missense probably damaging 0.99
R1840:Lgi3 UTSW 14 70,772,216 (GRCm39) splice site probably null
R1930:Lgi3 UTSW 14 70,773,708 (GRCm39) missense probably damaging 0.98
R1931:Lgi3 UTSW 14 70,773,708 (GRCm39) missense probably damaging 0.98
R2474:Lgi3 UTSW 14 70,770,689 (GRCm39) critical splice donor site probably null
R4672:Lgi3 UTSW 14 70,771,897 (GRCm39) missense possibly damaging 0.62
R5979:Lgi3 UTSW 14 70,773,900 (GRCm39) missense probably damaging 1.00
R6385:Lgi3 UTSW 14 70,768,610 (GRCm39) missense possibly damaging 0.66
R7146:Lgi3 UTSW 14 70,770,832 (GRCm39) missense probably damaging 1.00
R7314:Lgi3 UTSW 14 70,769,552 (GRCm39) missense probably damaging 1.00
R7712:Lgi3 UTSW 14 70,768,551 (GRCm39) missense unknown
R8124:Lgi3 UTSW 14 70,772,178 (GRCm39) missense probably damaging 1.00
R8417:Lgi3 UTSW 14 70,772,246 (GRCm39) missense probably benign 0.00
R8826:Lgi3 UTSW 14 70,768,712 (GRCm39) critical splice donor site probably null
R8881:Lgi3 UTSW 14 70,770,282 (GRCm39) missense probably damaging 1.00
R9186:Lgi3 UTSW 14 70,772,193 (GRCm39) missense probably damaging 1.00
Protein Function and Prediction

LGI3 is a member of the LGI/epitempin family (1). LGI3 has been shown to regulate the internalization of beta-amyloid protein and transferrin (2-4).  It is proposed that LGI3 is involved in endocytosis in the brain (2). 

Studies downregulating the LGI3 complex (with Flo1) disrupted beta-amyloid precursor protein trafficking to late endosomes and the formation of exosome, indicating a role for LGI3 in intracellular transport via its interaction with the co-factor Flo1 (2).  An association with syntaxin 1 at synapses indicates that LGI3 may have a role in the regulation of exocytosis (5). Knockdown of LGI3 resulted in decreased neurite outgrowth; LGI3 overexpression resulted in increased neurite outgrowth (6).  In another study, knockdown of LGI3 in 3T3-L1 cells increased the lipid content in adipocytes and adipogenic differentiation markers were upregulated, indicating a negative regulatory role for LGI3 in adipogenesis (1).
Expression/Localization

LGI3 is a secreted protein (1). Semiquantitative PCR determined that, in human tissues, LGI3 is ubiquitously expressed with highest expression in the brain and lung (7). In situ hybridization of adult mouse brain determined that Lgi3 is expressed at high levels in the facial nerve nucleus, while it is expressed at lower levels in other brain regions (8).
References
Posted On 2012-10-05
Science Writer Anne Murray