Incidental Mutation 'R2424:Plxna2'
ID 249463
Institutional Source Beutler Lab
Gene Symbol Plxna2
Ensembl Gene ENSMUSG00000026640
Gene Name plexin A2
Synonyms PlexA2, 2810428A13Rik, Plxn2, OCT
MMRRC Submission 040386-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R2424 (G1)
Quality Score 170
Status Validated
Chromosome 1
Chromosomal Location 194302020-194499177 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 194431625 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Phenylalanine at position 538 (S538F)
Ref Sequence ENSEMBL: ENSMUSP00000027952 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000027952]
AlphaFold P70207
PDB Structure Plexin A2 / Semaphorin 6A complex [X-RAY DIFFRACTION]
Mouse Plexin A2 extracellular domain [X-RAY DIFFRACTION]
Mouse Plexin A2, extracellular domains 1-4 [X-RAY DIFFRACTION]
Plexin A2 in complex with Semaphorin 6A [X-RAY DIFFRACTION]
Complex of mouse Plexin A2 - Semaphorin 3A - Neuropilin-1 [X-RAY DIFFRACTION]
Predicted Effect probably damaging
Transcript: ENSMUST00000027952
AA Change: S538F

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000027952
Gene: ENSMUSG00000026640
AA Change: S538F

DomainStartEndE-ValueType
low complexity region 16 29 N/A INTRINSIC
Sema 50 492 1.65e-132 SMART
PSI 510 560 8e-12 SMART
PSI 655 702 6.35e-6 SMART
PSI 803 856 1.24e-8 SMART
IPT 857 952 6.36e-21 SMART
IPT 953 1038 1.02e-24 SMART
IPT 1040 1140 1.48e-21 SMART
IPT 1142 1237 8.81e-6 SMART
transmembrane domain 1238 1260 N/A INTRINSIC
Pfam:Plexin_cytopl 1311 1864 1.9e-261 PFAM
Meta Mutation Damage Score 0.7688 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.5%
  • 10x: 97.1%
  • 20x: 94.3%
Validation Efficiency 100% (64/64)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele show abnormal granule cell migration in the adult cerebellum and aberrant projection of mossy fibers in hippocampal slices. Mice homozygous for an ENU-induced allele are smaller and show granule cell migration defects and mild ataxia with incomplete penetrance. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aacs A G 5: 125,590,159 (GRCm39) probably null Het
Acot3 G T 12: 84,100,638 (GRCm39) R138L probably damaging Het
Ago3 A G 4: 126,298,040 (GRCm39) V160A probably damaging Het
Akap9 A C 5: 4,115,279 (GRCm39) E166D probably damaging Het
Arid5a T C 1: 36,357,582 (GRCm39) Y136H probably damaging Het
Ascc3 T C 10: 50,494,297 (GRCm39) V244A probably benign Het
Atp10a A T 7: 58,444,303 (GRCm39) H560L probably benign Het
Btbd6 A G 12: 112,941,980 (GRCm39) T482A probably benign Het
Cacna1d A T 14: 29,770,980 (GRCm39) Y1828N probably damaging Het
Capzb A G 4: 138,921,441 (GRCm39) M1V probably null Het
Cdh9 T G 15: 16,850,440 (GRCm39) F524L probably damaging Het
Ctnna1 T C 18: 35,386,760 (GRCm39) S846P probably benign Het
Dab1 C T 4: 104,588,948 (GRCm39) A524V probably benign Het
Dock7 T A 4: 98,833,544 (GRCm39) R1886* probably null Het
Dpp3 A T 19: 4,957,735 (GRCm39) L711* probably null Het
Dst T A 1: 34,206,141 (GRCm39) I566N probably damaging Het
Eif2b3 T A 4: 116,928,045 (GRCm39) S421R probably benign Het
Epg5 T C 18: 78,011,828 (GRCm39) V825A probably benign Het
Eya1 T A 1: 14,341,072 (GRCm39) probably benign Het
Fam187a T C 11: 102,776,780 (GRCm39) Y195H probably damaging Het
Fbn2 C T 18: 58,336,859 (GRCm39) C132Y probably damaging Het
Fbxw21 A T 9: 108,986,587 (GRCm39) Y97* probably null Het
Grin1 A T 2: 25,208,664 (GRCm39) C79S probably null Het
Haao T A 17: 84,142,991 (GRCm39) Y118F probably damaging Het
Il11ra1 T A 4: 41,768,222 (GRCm39) S378T probably damaging Het
Kcnj5 A T 9: 32,234,116 (GRCm39) N66K probably damaging Het
Kif21a T A 15: 90,855,399 (GRCm39) N668I probably damaging Het
Kprp A T 3: 92,732,912 (GRCm39) L46Q probably damaging Het
Lama1 C T 17: 68,105,660 (GRCm39) T2056I probably benign Het
Madd G C 2: 90,996,967 (GRCm39) D824E probably damaging Het
Mapk9 A G 11: 49,754,499 (GRCm39) N84S probably damaging Het
Mrpl39 A G 16: 84,527,748 (GRCm39) V160A probably benign Het
Mrpl9 T C 3: 94,351,113 (GRCm39) S98P probably benign Het
Mybpc3 A T 2: 90,966,138 (GRCm39) M1233L probably benign Het
Neb A G 2: 52,099,671 (GRCm39) probably benign Het
Ngly1 A G 14: 16,290,721 (GRCm38) probably null Het
Nt5c1b A T 12: 10,420,072 (GRCm39) T4S probably damaging Het
Obscn T C 11: 58,885,277 (GRCm39) probably benign Het
Or2h2c T C 17: 37,422,408 (GRCm39) I155M probably benign Het
Or4k15b T C 14: 50,272,281 (GRCm39) Y193C probably damaging Het
Or8b1b T C 9: 38,376,128 (GRCm39) S264P probably damaging Het
Or8g53 A G 9: 39,683,593 (GRCm39) F168L probably benign Het
Otog A T 7: 45,947,593 (GRCm39) K64* probably null Het
Papola A G 12: 105,793,311 (GRCm39) T544A probably benign Het
Phc1 A G 6: 122,297,002 (GRCm39) V790A probably damaging Het
Phf3 G T 1: 30,845,430 (GRCm39) R1252S probably damaging Het
Phf8-ps T C 17: 33,284,730 (GRCm39) T691A probably benign Het
Rgs17 T A 10: 5,783,111 (GRCm39) I159F probably damaging Het
Rgs17 T A 10: 5,792,560 (GRCm39) E62V probably benign Het
Rnase1 A G 14: 51,383,004 (GRCm39) Y117H possibly damaging Het
Rnf214 T C 9: 45,811,096 (GRCm39) D189G probably damaging Het
Sema4b A G 7: 79,869,023 (GRCm39) N365S probably damaging Het
Setd2 A G 9: 110,446,590 (GRCm39) H2480R probably benign Het
Slc27a6 G T 18: 58,738,189 (GRCm39) C415F probably benign Het
Stim1 A G 7: 102,057,612 (GRCm39) I142V probably benign Het
Supt5 T C 7: 28,014,590 (GRCm39) I1070V possibly damaging Het
Tbp T C 17: 15,733,795 (GRCm39) F174L possibly damaging Het
Tex26 A G 5: 149,393,913 (GRCm39) probably benign Het
Tmem132d A G 5: 127,941,663 (GRCm39) V479A probably benign Het
Ttn T C 2: 76,711,489 (GRCm39) probably benign Het
Urb2 T A 8: 124,757,165 (GRCm39) N957K probably benign Het
Usp24 T C 4: 106,256,310 (GRCm39) probably null Het
Vmn2r114 T C 17: 23,515,842 (GRCm39) T550A possibly damaging Het
Vmn2r72 A G 7: 85,400,161 (GRCm39) V296A probably damaging Het
Vmn2r91 C A 17: 18,356,431 (GRCm39) Y699* probably null Het
Other mutations in Plxna2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00227:Plxna2 APN 1 194,326,965 (GRCm39) missense probably damaging 1.00
IGL00332:Plxna2 APN 1 194,472,138 (GRCm39) missense probably damaging 0.98
IGL00392:Plxna2 APN 1 194,482,876 (GRCm39) missense probably damaging 1.00
IGL00432:Plxna2 APN 1 194,326,404 (GRCm39) missense probably benign 0.03
IGL00704:Plxna2 APN 1 194,433,769 (GRCm39) missense probably damaging 0.99
IGL00737:Plxna2 APN 1 194,428,547 (GRCm39) splice site probably benign
IGL01078:Plxna2 APN 1 194,469,001 (GRCm39) unclassified probably benign
IGL01354:Plxna2 APN 1 194,444,743 (GRCm39) missense probably benign 0.02
IGL01432:Plxna2 APN 1 194,326,626 (GRCm39) missense possibly damaging 0.58
IGL01459:Plxna2 APN 1 194,446,878 (GRCm39) missense probably benign 0.00
IGL01525:Plxna2 APN 1 194,394,619 (GRCm39) missense probably benign 0.00
IGL01656:Plxna2 APN 1 194,472,469 (GRCm39) missense possibly damaging 0.52
IGL01825:Plxna2 APN 1 194,471,210 (GRCm39) missense probably damaging 0.98
IGL01862:Plxna2 APN 1 194,326,258 (GRCm39) missense possibly damaging 0.87
IGL01899:Plxna2 APN 1 194,433,796 (GRCm39) missense probably damaging 1.00
IGL01996:Plxna2 APN 1 194,482,084 (GRCm39) missense probably damaging 0.99
IGL02123:Plxna2 APN 1 194,476,691 (GRCm39) missense probably damaging 1.00
IGL02226:Plxna2 APN 1 194,326,732 (GRCm39) missense probably damaging 1.00
IGL02227:Plxna2 APN 1 194,434,397 (GRCm39) missense probably damaging 1.00
IGL02415:Plxna2 APN 1 194,326,272 (GRCm39) missense probably damaging 1.00
IGL02440:Plxna2 APN 1 194,428,458 (GRCm39) missense probably benign 0.10
IGL02545:Plxna2 APN 1 194,468,998 (GRCm39) unclassified probably benign
IGL02553:Plxna2 APN 1 194,433,746 (GRCm39) missense probably benign 0.08
IGL02882:Plxna2 APN 1 194,444,878 (GRCm39) missense probably damaging 1.00
IGL02946:Plxna2 APN 1 194,431,617 (GRCm39) splice site probably benign
IGL03062:Plxna2 APN 1 194,444,858 (GRCm39) missense possibly damaging 0.72
IGL03095:Plxna2 APN 1 194,483,435 (GRCm39) missense probably damaging 1.00
IGL03293:Plxna2 APN 1 194,487,253 (GRCm39) missense probably damaging 0.99
G1Funyon:Plxna2 UTSW 1 194,472,483 (GRCm39) missense probably benign 0.01
PIT4514001:Plxna2 UTSW 1 194,477,245 (GRCm39) missense probably benign 0.00
R0024:Plxna2 UTSW 1 194,326,303 (GRCm39) missense possibly damaging 0.57
R0040:Plxna2 UTSW 1 194,326,204 (GRCm39) missense probably benign 0.13
R0040:Plxna2 UTSW 1 194,326,204 (GRCm39) missense probably benign 0.13
R0063:Plxna2 UTSW 1 194,327,247 (GRCm39) missense probably benign 0.00
R0063:Plxna2 UTSW 1 194,327,247 (GRCm39) missense probably benign 0.00
R0217:Plxna2 UTSW 1 194,326,906 (GRCm39) missense probably damaging 1.00
R0316:Plxna2 UTSW 1 194,326,458 (GRCm39) missense probably damaging 1.00
R0440:Plxna2 UTSW 1 194,326,712 (GRCm39) nonsense probably null
R0505:Plxna2 UTSW 1 194,326,656 (GRCm39) missense possibly damaging 0.93
R0568:Plxna2 UTSW 1 194,433,694 (GRCm39) missense probably benign 0.00
R0669:Plxna2 UTSW 1 194,471,145 (GRCm39) missense probably damaging 0.99
R0674:Plxna2 UTSW 1 194,331,783 (GRCm39) missense probably benign 0.00
R0885:Plxna2 UTSW 1 194,326,864 (GRCm39) missense probably benign
R0898:Plxna2 UTSW 1 194,479,332 (GRCm39) missense probably damaging 1.00
R0940:Plxna2 UTSW 1 194,482,863 (GRCm39) missense probably benign 0.01
R1061:Plxna2 UTSW 1 194,326,401 (GRCm39) missense probably damaging 1.00
R1067:Plxna2 UTSW 1 194,462,818 (GRCm39) splice site probably null
R1222:Plxna2 UTSW 1 194,482,957 (GRCm39) missense probably damaging 1.00
R1345:Plxna2 UTSW 1 194,326,794 (GRCm39) missense probably damaging 1.00
R1363:Plxna2 UTSW 1 194,487,247 (GRCm39) nonsense probably null
R1432:Plxna2 UTSW 1 194,449,771 (GRCm39) missense probably benign 0.10
R1434:Plxna2 UTSW 1 194,433,848 (GRCm39) splice site probably benign
R1597:Plxna2 UTSW 1 194,431,614 (GRCm39) splice site probably benign
R1719:Plxna2 UTSW 1 194,326,678 (GRCm39) missense possibly damaging 0.93
R1778:Plxna2 UTSW 1 194,493,278 (GRCm39) missense probably benign 0.01
R1795:Plxna2 UTSW 1 194,488,611 (GRCm39) missense probably damaging 0.99
R1819:Plxna2 UTSW 1 194,472,494 (GRCm39) missense probably benign 0.03
R1926:Plxna2 UTSW 1 194,444,758 (GRCm39) missense probably benign 0.02
R1966:Plxna2 UTSW 1 194,327,008 (GRCm39) missense possibly damaging 0.91
R1987:Plxna2 UTSW 1 194,326,297 (GRCm39) missense probably damaging 1.00
R1988:Plxna2 UTSW 1 194,326,297 (GRCm39) missense probably damaging 1.00
R2034:Plxna2 UTSW 1 194,462,902 (GRCm39) missense probably benign 0.00
R2131:Plxna2 UTSW 1 194,327,058 (GRCm39) missense probably benign 0.01
R2171:Plxna2 UTSW 1 194,482,925 (GRCm39) missense probably damaging 1.00
R2217:Plxna2 UTSW 1 194,480,056 (GRCm39) missense probably damaging 1.00
R2311:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R2340:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R2342:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R2423:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R2425:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R2842:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R2971:Plxna2 UTSW 1 194,480,039 (GRCm39) missense probably damaging 1.00
R3236:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R3731:Plxna2 UTSW 1 194,471,193 (GRCm39) missense probably benign 0.42
R3783:Plxna2 UTSW 1 194,489,829 (GRCm39) missense probably damaging 1.00
R3784:Plxna2 UTSW 1 194,326,925 (GRCm39) missense probably benign
R3787:Plxna2 UTSW 1 194,326,242 (GRCm39) missense probably benign 0.10
R3845:Plxna2 UTSW 1 194,476,098 (GRCm39) missense probably damaging 0.96
R3927:Plxna2 UTSW 1 194,428,465 (GRCm39) missense probably benign 0.02
R3930:Plxna2 UTSW 1 194,477,218 (GRCm39) missense probably benign 0.17
R3964:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R3980:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4067:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4120:Plxna2 UTSW 1 194,462,935 (GRCm39) missense probably damaging 1.00
R4231:Plxna2 UTSW 1 194,326,762 (GRCm39) missense probably damaging 1.00
R4257:Plxna2 UTSW 1 194,327,083 (GRCm39) missense probably damaging 1.00
R4396:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4397:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4418:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4444:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4446:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4482:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4487:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4489:Plxna2 UTSW 1 194,431,625 (GRCm39) missense probably damaging 1.00
R4571:Plxna2 UTSW 1 194,493,296 (GRCm39) missense possibly damaging 0.91
R4622:Plxna2 UTSW 1 194,494,458 (GRCm39) missense probably benign
R4623:Plxna2 UTSW 1 194,494,458 (GRCm39) missense probably benign
R4684:Plxna2 UTSW 1 194,444,902 (GRCm39) missense probably benign 0.42
R4688:Plxna2 UTSW 1 194,326,753 (GRCm39) missense probably damaging 1.00
R4855:Plxna2 UTSW 1 194,480,040 (GRCm39) missense probably benign 0.39
R4876:Plxna2 UTSW 1 194,326,083 (GRCm39) missense probably benign 0.02
R5161:Plxna2 UTSW 1 194,433,712 (GRCm39) missense probably benign
R5207:Plxna2 UTSW 1 194,471,207 (GRCm39) missense probably benign 0.19
R5479:Plxna2 UTSW 1 194,476,181 (GRCm39) missense probably benign
R5931:Plxna2 UTSW 1 194,493,178 (GRCm39) missense probably damaging 1.00
R6026:Plxna2 UTSW 1 194,482,122 (GRCm39) missense probably damaging 1.00
R6029:Plxna2 UTSW 1 194,481,883 (GRCm39) missense probably damaging 1.00
R6029:Plxna2 UTSW 1 194,476,735 (GRCm39) missense probably benign 0.00
R6059:Plxna2 UTSW 1 194,493,279 (GRCm39) missense possibly damaging 0.79
R6238:Plxna2 UTSW 1 194,472,504 (GRCm39) missense probably benign 0.01
R6322:Plxna2 UTSW 1 194,436,675 (GRCm39) missense possibly damaging 0.89
R6668:Plxna2 UTSW 1 194,492,396 (GRCm39) missense possibly damaging 0.68
R6709:Plxna2 UTSW 1 194,472,074 (GRCm39) missense probably benign 0.01
R6748:Plxna2 UTSW 1 194,476,490 (GRCm39) splice site probably null
R6838:Plxna2 UTSW 1 194,487,222 (GRCm39) missense possibly damaging 0.90
R6844:Plxna2 UTSW 1 194,476,136 (GRCm39) missense probably benign 0.08
R7069:Plxna2 UTSW 1 194,476,212 (GRCm39) missense possibly damaging 0.51
R7122:Plxna2 UTSW 1 194,326,876 (GRCm39) nonsense probably null
R7145:Plxna2 UTSW 1 194,331,830 (GRCm39) missense probably benign 0.31
R7189:Plxna2 UTSW 1 194,483,366 (GRCm39) missense possibly damaging 0.58
R7207:Plxna2 UTSW 1 194,326,327 (GRCm39) missense probably damaging 1.00
R7232:Plxna2 UTSW 1 194,394,568 (GRCm39) missense probably damaging 1.00
R7234:Plxna2 UTSW 1 194,488,698 (GRCm39) missense probably damaging 0.96
R7246:Plxna2 UTSW 1 194,326,590 (GRCm39) missense possibly damaging 0.74
R7255:Plxna2 UTSW 1 194,434,411 (GRCm39) missense probably benign 0.03
R7283:Plxna2 UTSW 1 194,327,191 (GRCm39) missense probably damaging 0.99
R7288:Plxna2 UTSW 1 194,479,227 (GRCm39) missense probably damaging 1.00
R7361:Plxna2 UTSW 1 194,482,087 (GRCm39) missense probably damaging 1.00
R7424:Plxna2 UTSW 1 194,488,647 (GRCm39) missense probably damaging 0.98
R7501:Plxna2 UTSW 1 194,326,203 (GRCm39) missense possibly damaging 0.95
R7528:Plxna2 UTSW 1 194,494,464 (GRCm39) missense probably damaging 1.00
R7529:Plxna2 UTSW 1 194,326,179 (GRCm39) missense probably benign 0.25
R7532:Plxna2 UTSW 1 194,327,127 (GRCm39) missense probably benign 0.13
R7959:Plxna2 UTSW 1 194,493,270 (GRCm39) missense probably damaging 1.00
R7959:Plxna2 UTSW 1 194,476,172 (GRCm39) frame shift probably null
R7960:Plxna2 UTSW 1 194,476,172 (GRCm39) frame shift probably null
R8261:Plxna2 UTSW 1 194,431,724 (GRCm39) missense probably damaging 1.00
R8301:Plxna2 UTSW 1 194,472,483 (GRCm39) missense probably benign 0.01
R8463:Plxna2 UTSW 1 194,326,354 (GRCm39) missense probably damaging 1.00
R8519:Plxna2 UTSW 1 194,476,266 (GRCm39) missense probably damaging 1.00
R8836:Plxna2 UTSW 1 194,479,243 (GRCm39) missense possibly damaging 0.94
R9010:Plxna2 UTSW 1 194,471,217 (GRCm39) missense possibly damaging 0.95
R9034:Plxna2 UTSW 1 194,476,197 (GRCm39) missense probably damaging 1.00
R9254:Plxna2 UTSW 1 194,492,474 (GRCm39) missense probably damaging 1.00
R9274:Plxna2 UTSW 1 194,471,136 (GRCm39) missense probably damaging 1.00
R9379:Plxna2 UTSW 1 194,492,474 (GRCm39) missense probably damaging 1.00
R9385:Plxna2 UTSW 1 194,431,724 (GRCm39) missense possibly damaging 0.95
R9422:Plxna2 UTSW 1 194,326,730 (GRCm39) missense probably damaging 1.00
R9451:Plxna2 UTSW 1 194,326,692 (GRCm39) missense probably benign 0.05
R9484:Plxna2 UTSW 1 194,327,202 (GRCm39) missense probably damaging 1.00
X0027:Plxna2 UTSW 1 194,326,741 (GRCm39) missense probably damaging 1.00
Z1088:Plxna2 UTSW 1 194,446,847 (GRCm39) missense probably benign 0.06
Z1088:Plxna2 UTSW 1 194,326,749 (GRCm39) missense possibly damaging 0.56
Predicted Primers PCR Primer
(F):5'- GAGCTGTCCTTCTTAAGTACCC -3'
(R):5'- AAAGAAGTTTGCTCTGTGCTC -3'

Sequencing Primer
(F):5'- AACCAGCATCTTGGCTTGG -3'
(R):5'- TCTGTGCTCCGGTCGGTC -3'
Posted On 2014-11-12