Incidental Mutation 'A4554:Fgl2'
ID 96
Institutional Source Beutler Lab
Gene Symbol Fgl2
Ensembl Gene ENSMUSG00000039899
Gene Name fibrinogen-like protein 2
Synonyms
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.295) question?
Stock # A4554 of strain gemini
Quality Score
Status Validated
Chromosome 5
Chromosomal Location 21577671-21583384 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 21577776 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Glutamic Acid to Glycine at position 21 (E21G)
Ref Sequence ENSEMBL: ENSMUSP00000046131 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000030552] [ENSMUST00000035799] [ENSMUST00000115245]
AlphaFold P12804
Predicted Effect probably benign
Transcript: ENSMUST00000030552
SMART Domains Protein: ENSMUSP00000030552
Gene: ENSMUSG00000064280

DomainStartEndE-ValueType
coiled coil region 1 33 N/A INTRINSIC
low complexity region 120 130 N/A INTRINSIC
coiled coil region 194 320 N/A INTRINSIC
low complexity region 333 342 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000035799
AA Change: E21G

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000046131
Gene: ENSMUSG00000039899
AA Change: E21G

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
low complexity region 54 70 N/A INTRINSIC
coiled coil region 71 158 N/A INTRINSIC
FBG 201 428 1.6e-131 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000115245
SMART Domains Protein: ENSMUSP00000110900
Gene: ENSMUSG00000064280

DomainStartEndE-ValueType
coiled coil region 1 33 N/A INTRINSIC
low complexity region 120 130 N/A INTRINSIC
coiled coil region 194 320 N/A INTRINSIC
low complexity region 333 342 N/A INTRINSIC
coiled coil region 438 477 N/A INTRINSIC
coiled coil region 549 595 N/A INTRINSIC
coiled coil region 617 663 N/A INTRINSIC
coiled coil region 690 720 N/A INTRINSIC
coiled coil region 770 793 N/A INTRINSIC
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 63.0%
Validation Efficiency 84% (92/109)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a secreted protein that is similar to the beta- and gamma-chains of fibrinogen. The carboxyl-terminus of the encoded protein consists of the fibrinogen-related domains (FRED). The encoded protein forms a tetrameric complex which is stabilized by interchain disulfide bonds. This protein may play a role in physiologic functions at mucosal sites. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mice for one allele have unaltered type 1 immunity responses. Homozygous null mice for another allele show partial embryonic lethality, hemorrhage at implantation sites, decreased susceptibility to hepatitis virus infection and prolongedsurvival of heart grafts. [provided by MGI curators]
Allele List at MGI

All alleles(2) : Targeted, knock-out(1) Targeted, other(1)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Asap1 T C 15: 63,996,560 (GRCm39) probably benign Het
Bpifb5 A T 2: 154,069,100 (GRCm39) Y139F possibly damaging Homo
Chd2 A C 7: 73,130,716 (GRCm39) V782G probably benign Homo
Chst4 G T 8: 110,756,520 (GRCm39) Q448K probably benign Homo
Dido1 T C 2: 180,317,164 (GRCm39) K8E probably damaging Homo
Evpl A G 11: 116,111,660 (GRCm39) L2010P probably damaging Homo
Greb1l A T 18: 10,532,862 (GRCm39) M919L possibly damaging Homo
Kel T A 6: 41,674,353 (GRCm39) D359V possibly damaging Homo
Lmtk2 A G 5: 144,103,135 (GRCm39) D298G possibly damaging Homo
Masp1 A T 16: 23,273,690 (GRCm39) probably null Homo
Mrgprb8 A T 7: 48,039,156 (GRCm39) I276F probably damaging Homo
Nde1 T C 16: 14,006,274 (GRCm39) probably benign Homo
Rbck1 G T 2: 152,161,092 (GRCm39) N385K probably damaging Homo
Senp6 G T 9: 80,055,740 (GRCm39) probably benign Het
Tm4sf4 T A 3: 57,345,188 (GRCm39) probably null Homo
Ubn2 A T 6: 38,461,045 (GRCm39) H488L probably damaging Homo
Vmn2r120 A G 17: 57,832,715 (GRCm39) F155L probably benign Homo
Vmn2r65 T A 7: 84,595,791 (GRCm39) T298S probably damaging Homo
Other mutations in Fgl2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01622:Fgl2 APN 5 21,578,175 (GRCm39) missense possibly damaging 0.57
IGL01623:Fgl2 APN 5 21,578,175 (GRCm39) missense possibly damaging 0.57
IGL02056:Fgl2 APN 5 21,580,543 (GRCm39) missense probably damaging 0.99
IGL03128:Fgl2 APN 5 21,578,291 (GRCm39) missense probably benign
R0049:Fgl2 UTSW 5 21,580,661 (GRCm39) missense possibly damaging 0.95
R0049:Fgl2 UTSW 5 21,580,661 (GRCm39) missense possibly damaging 0.95
R0052:Fgl2 UTSW 5 21,580,347 (GRCm39) missense probably damaging 1.00
R0052:Fgl2 UTSW 5 21,580,347 (GRCm39) missense probably damaging 1.00
R0149:Fgl2 UTSW 5 21,580,783 (GRCm39) missense probably damaging 1.00
R0316:Fgl2 UTSW 5 21,580,521 (GRCm39) missense possibly damaging 0.82
R1336:Fgl2 UTSW 5 21,578,181 (GRCm39) missense possibly damaging 0.52
R1703:Fgl2 UTSW 5 21,577,730 (GRCm39) missense possibly damaging 0.89
R1893:Fgl2 UTSW 5 21,580,669 (GRCm39) missense probably benign 0.01
R2371:Fgl2 UTSW 5 21,580,816 (GRCm39) missense probably damaging 1.00
R4803:Fgl2 UTSW 5 21,580,918 (GRCm39) missense probably benign 0.00
R5250:Fgl2 UTSW 5 21,580,521 (GRCm39) missense possibly damaging 0.82
R5422:Fgl2 UTSW 5 21,580,808 (GRCm39) missense probably damaging 1.00
R6759:Fgl2 UTSW 5 21,578,256 (GRCm39) missense probably benign 0.00
R7808:Fgl2 UTSW 5 21,578,229 (GRCm39) missense possibly damaging 0.53
R7812:Fgl2 UTSW 5 21,577,896 (GRCm39) missense probably benign 0.01
R7838:Fgl2 UTSW 5 21,577,752 (GRCm39) missense probably benign 0.01
R8177:Fgl2 UTSW 5 21,578,307 (GRCm39) critical splice donor site probably null
R8725:Fgl2 UTSW 5 21,580,677 (GRCm39) nonsense probably null
R8727:Fgl2 UTSW 5 21,580,677 (GRCm39) nonsense probably null
R9114:Fgl2 UTSW 5 21,580,363 (GRCm39) missense probably damaging 1.00
R9198:Fgl2 UTSW 5 21,577,920 (GRCm39) missense probably damaging 0.96
R9513:Fgl2 UTSW 5 21,580,790 (GRCm39) nonsense probably null
R9606:Fgl2 UTSW 5 21,577,991 (GRCm39) missense possibly damaging 0.87
X0017:Fgl2 UTSW 5 21,580,650 (GRCm39) missense probably damaging 0.98
X0026:Fgl2 UTSW 5 21,580,711 (GRCm39) missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 106 of the Fgl2 transcript in exon 1 of 2 total exons. The mutated nucleotide causes a glutamic acid to glycine substitution at amino acid 21 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Fgl2 gene encodes a 432 amino acid protein known as fibroleukin that contains one fibrinogen C-terminal domain at amino acids 197-429. Fibroleukin converts prothrombin to thrombin and forms a disulfide-linked homotetramer. The protein is constitutively expressed in cytotoxic T cells and is upregulated in macrophages during infection by mouse hepatitis virus strain 3 (MHV-3) (Uniprot P12804). Homozygous null mice for one allele have unaltered type 1 immunity responses. Homozygous null mice for another allele show partial embryonic lethality, hemorrhage at implantation sites, decreased susceptibility to hepatitis virus infection and prolonged survival of heart grafts.
 
The E21G change is predicted to be probably benign by the PolyPhen program.
Posted On 2010-03-16