Gene Page:VARS2
Summary?
| GeneID | 57176 |
| Symbol | VARS2 |
| Synonyms | COXPD20|VALRS|VARS2L|VARSL |
| Description | valyl-tRNA synthetase 2, mitochondrial |
| Reference | MIM:612802|HGNC:HGNC:21642|Ensembl:ENSG00000137411|HPRD:11670|Vega:OTTHUMG00000031263 |
| Gene type | protein-coding |
| Map location | 6p21.33 |
| Pascal p-value | 1E-12 |
| Sherlock p-value | 0.975 |
| eGene | Anterior cingulate cortex BA24 Caudate basal ganglia Cerebellar Hemisphere Cerebellum Cortex Frontal Cortex BA9 Hippocampus Hypothalamus Nucleus accumbens basal ganglia Putamen basal ganglia Myers' cis & trans Meta |
Gene in Data Sources
| 基因集名称 | Method of gene set | Description | Info |
|---|---|---|---|
| CV:PGCnp | Genome-wide Association Study | GWAS | |
| GSMA_I | Genome scan meta-analysis | Psr: 0.033 |
Section I. Genetics and epigenetics annotation
eQTL annotation
eQTL annotation| SNP ID | Chromosome | Position | eGene | Gene Entrez ID | pvalue | qvalue | TSS distance | eQTL type |
|---|---|---|---|---|---|---|---|---|
| rs1264344 | chr6 | 30800576 | VARS2 | 57176 | 0.19 | cis | ||
| rs7738138 | chr6 | 30887343 | VARS2 | 57176 | 0.02 | cis | ||
| rs753725 | chr6 | 30890870 | VARS2 | 57176 | 0.01 | cis | ||
| rs2532921 | chr6 | 30922569 | VARS2 | 57176 | 0 | cis | ||
| rs2532921 | chr6 | 30922569 | VARS2 | 57176 | 0.13 | trans | ||
| rs1264345 | 6 | 30800068 | VARS2 | ENSG00000137411.12 | 3.13E-7 | 0 | -81914 | gtex_brain_ba24 |
| rs1264344 | 6 | 30800577 | VARS2 | ENSG00000137411.12 | 1.989E-7 | 0 | -81405 | gtex_brain_ba24 |
| rs540795529 | 6 | 30800869 | VARS2 | ENSG00000137411.12 | 1.989E-7 | 0 | -81113 | gtex_brain_ba24 |
| rs1264342 | 6 | 30802017 | VARS2 | ENSG00000137411.12 | 8.653E-10 | 0 | -79965 | gtex_brain_ba24 |
| rs2535338 | 6 | 30804932 | VARS2 | ENSG00000137411.12 | 1.989E-7 | 0 | -77050 | gtex_brain_ba24 |
| rs2517582 | 6 | 30808762 | VARS2 | ENSG00000137411.12 | 8.104E-9 | 0 | -73220 | gtex_brain_ba24 |
| rs2535337 | 6 | 30810084 | VARS2 | ENSG00000137411.12 | 2.687E-10 | 0 | -71898 | gtex_brain_ba24 |
| rs2535336 | 6 | 30810654 | VARS2 | ENSG00000137411.12 | 2.096E-10 | 0 | -71328 | gtex_brain_ba24 |
| rs2535335 | 6 | 30812497 | VARS2 | ENSG00000137411.12 | 1.859E-10 | 0 | 69485 | gtex_brain_ba24 |
| rs2517577 | 6 | 30813292 | VARS2 | ENSG00000137411.12 | 2.63E-10 | 0 | 68690 | gtex_brain_ba24 |
| rs2844664 | 6 | 30815945 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -66037年 | gtex_brain_ba24 |
| rs2844663 | 6 | 30815951 | VARS2 | ENSG00000137411.12 | 2.104E-10 | 0 | 66031 | gtex_brain_ba24 |
| rs2535331 | 6 | 30816270 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 65712 | gtex_brain_ba24 |
| rs2844662 | 6 | 30817879 | VARS2 | ENSG00000137411.12 | 2.104E-10 | 0 | 64103 | gtex_brain_ba24 |
| rs2517575 | 6 | 30819465 | VARS2 | ENSG00000137411.12 | 2.104E-10 | 0 | 62517 | gtex_brain_ba24 |
| rs2535330 | 6 | 30824642 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -57340 | gtex_brain_ba24 |
| rs2844658 | 6 | 30825812 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -56170 | gtex_brain_ba24 |
| rs2535327 | 6 | 30826904 | VARS2 | ENSG00000137411.12 | 4.44E-10 | 0 | -55078 | gtex_brain_ba24 |
| rs2535326 | 6 | 30832063 | VARS2 | ENSG00000137411.12 | 2.104E-10 | 0 | -49919 | gtex_brain_ba24 |
| rs2535325 | 6 | 30833081 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -48901 | gtex_brain_ba24 |
| rs9278786 | 6 | 30836489 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -45493 | gtex_brain_ba24 |
| rs2844655 | 6 | 30837538 | VARS2 | ENSG00000137411.12 | 4.44E-10 | 0 | -44444 | gtex_brain_ba24 |
| rs3130657 | 6 | 30837646 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -44336 | gtex_brain_ba24 |
| rs2844654 | 6 | 30838688 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -43294 | gtex_brain_ba24 |
| rs2535339 | 6 | 30839430 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -42552 | gtex_brain_ba24 |
| rs2517573 | 6 | 30840147 | VARS2 | ENSG00000137411.12 | 2.442E-10 | 0 | -41835 | gtex_brain_ba24 |
| rs9278790 | 6 | 30842095 | VARS2 | ENSG00000137411.12 | 2.404E-8 | 0 | -39887 | gtex_brain_ba24 |
| rs2535329 | 6 | 30842674 | VARS2 | ENSG00000137411.12 | 4.44E-10 | 0 | -39308 | gtex_brain_ba24 |
| rs1264334 | 6 | 30844260 | VARS2 | ENSG00000137411.12 | 2.104E-10 | 0 | -37722 | gtex_brain_ba24 |
| rs1264333 | 6 | 30844314 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -37668 | gtex_brain_ba24 |
| rs1264332 | 6 | 30845563 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -36419 | gtex_brain_ba24 |
| rs1264331 | 6 | 30846830 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -35152 | gtex_brain_ba24 |
| rs1264327 | 6 | 30850582 | VARS2 | ENSG00000137411.12 | 4.44E-10 | 0 | -31400 | gtex_brain_ba24 |
| rs1264320 | 6 | 30861000 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -20982 | gtex_brain_ba24 |
| rs1264317 | 6 | 30864700 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -17282 | gtex_brain_ba24 |
| rs1264311 | 6 | 30873041 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -8941 | gtex_brain_ba24 |
| rs1264309 | 6 | 30875899 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 6083 | gtex_brain_ba24 |
| rs1264307 | 6 | 30880757 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | -1225 | gtex_brain_ba24 |
| rs1264305 | 6 | 30882277 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 295 | gtex_brain_ba24 |
| rs1264303 | 6 | 30882513 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 531 | gtex_brain_ba24 |
| rs1264302 | 6 | 30882634 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 652 | gtex_brain_ba24 |
| rs1264301 | 6 | 30882781 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 799 | gtex_brain_ba24 |
| rs1264300 | 6 | 30882856 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 874 | gtex_brain_ba24 |
| rs1264299 | 6 | 30883920 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 1938 | gtex_brain_ba24 |
| rs527858296 | 6 | 30884331 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 2349 | gtex_brain_ba24 |
| rs1264298 | 6 | 30884436 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 2454 | gtex_brain_ba24 |
| rs1264297 | 6 | 30884806 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 2824 | gtex_brain_ba24 |
| rs9262288 | 6 | 30885639 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 3657 | gtex_brain_ba24 |
| rs9262289 | 6 | 30885686 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 3704 | gtex_brain_ba24 |
| rs9262290 | 6 | 30885821 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 3839 | gtex_brain_ba24 |
| rs374965024 | 6 | 30885839 | VARS2 | ENSG00000137411.12 | 4.196E-10 | 0 | 3857 | gtex_brain_ba24 |
| rs9262291 | 6 | 30886015 | VARS2 | ENSG00000137411.12 | 1.656E-10 | 0 | 4033 | gtex_brain_ba24 |
| rs9262292 | 6 | 30886079 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 4097 | gtex_brain_ba24 |
| rs9262293 | 6 | 30886350 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 4368 | gtex_brain_ba24 |
| rs9262294 | 6 | 30887207 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 5225 | gtex_brain_ba24 |
| rs7756286 | 6 | 30887311 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 5329 | gtex_brain_ba24 |
| rs7738138 | 6 | 30887344 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 5362 | gtex_brain_ba24 |
| rs2249459 | 6 | 30887988 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 6006 | gtex_brain_ba24 |
| rs2517468 | 6 | 30888169 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 6187 | gtex_brain_ba24 |
| rs2532943 | 6 | 30889120 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 7138 | gtex_brain_ba24 |
| rs2517466 | 6 | 30890055 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 8073 | gtex_brain_ba24 |
| rs887381 | 6 | 30890206 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 8224 | gtex_brain_ba24 |
| rs2074506 | 6 | 30890483 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 8501 | gtex_brain_ba24 |
| rs753726 | 6 | 30890569 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 8587 | gtex_brain_ba24 |
| rs9281079 | 6 | 30891705 | VARS2 | ENSG00000137411.12 | 1.734E-10 | 0 | 9723 | gtex_brain_ba24 |
| rs2532942 | 6 | 30892322 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 10340 | gtex_brain_ba24 |
| rs2252760 | 6 | 30892377 | VARS2 | ENSG00000137411.12 | 2.259E-10 | 0 | 10395 | gtex_brain_ba24 |
| rs2532940 | 6 | 30892592 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 10610 | gtex_brain_ba24 |
| rs2532939 | 6 | 30893226 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 11244 | gtex_brain_ba24 |
| rs2252856 | 6 | 30893251 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 11269 | gtex_brain_ba24 |
| rs2252863 | 6 | 30893428 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 11446 | gtex_brain_ba24 |
| rs2532938 | 6 | 30893831 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 11849 | gtex_brain_ba24 |
| rs2532937 | 6 | 30894344 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 12362 | gtex_brain_ba24 |
| rs2532936 | 6 | 30894408 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 12426 | gtex_brain_ba24 |
| rs72397672 | 6 | 30894416 | VARS2 | ENSG00000137411.12 | 1.447平台以及 | 0 | 12434 | gtex_brain_ba24 |
| rs2532935 | 6 | 30894573 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 12591 | gtex_brain_ba24 |
| rs2517463 | 6 | 30895264 | VARS2 | ENSG00000137411.12 | 8.782E-10 | 0 | 13282 | gtex_brain_ba24 |
| rs2532933 | 6 | 30895293 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 13311 | gtex_brain_ba24 |
| rs2394856 | 6 | 30895592 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 13610 | gtex_brain_ba24 |
| rs2532930 | 6 | 30895725 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 13743 | gtex_brain_ba24 |
| rs2517462 | 6 | 30896190 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 14208 | gtex_brain_ba24 |
| rs2517461 | 6 | 30896399 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 14417 | gtex_brain_ba24 |
| rs2532929 | 6 | 30897774 | VARS2 | ENSG00000137411.12 | 2.682E-9 | 0 | 15792 | gtex_brain_ba24 |
| rs2532928 | 6 | 30898295 | VARS2 | ENSG00000137411.12 | 2.695E-10 | 0 | 16313 | gtex_brain_ba24 |
| rs2532927 | 6 | 30898434 | VARS2 | ENSG00000137411.12 | 1.437E-9 | 0 | 16452 | gtex_brain_ba24 |
| rs2532926 | 6 | 30898441 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 16459 | gtex_brain_ba24 |
| rs2517457 | 6 | 30898442 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 16460 | gtex_brain_ba24 |
| rs2844652 | 6 | 30898687 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 16705 | gtex_brain_ba24 |
| rs2253718 | 6 | 30900427 | VARS2 | ENSG00000137411.12 | 8.985E-7 | 0 | 18445 | gtex_brain_ba24 |
| rs2243739 | 6 | 30909408 | VARS2 | ENSG00000137411.12 | 2.754E-10 | 0 | 27426 | gtex_brain_ba24 |
| rs2844702 | 6 | 30912481 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 30499 | gtex_brain_ba24 |
| rs2844699 | 6 | 30918400 | VARS2 | ENSG00000137411.12 | 2.798E-10 | 0 | 36418 | gtex_brain_ba24 |
| rs2517449 | 6 | 30919701 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 37719 | gtex_brain_ba24 |
| rs2240804 | 6 | 30920890 | VARS2 | ENSG00000137411.12 | 4.44E-10 | 0 | 38908 | gtex_brain_ba24 |
| rs2532921 | 6 | 30922570 | VARS2 | ENSG00000137411.12 | 2.692E-10 | 0 | 40588 | gtex_brain_ba24 |
| rs17189763 | 6 | 30923527 | VARS2 | ENSG00000137411.12 | 4.44E-10 | 0 | 41545 | gtex_brain_ba24 |
| rs2532920 | 6 | 30923629 | VARS2 | ENSG00000137411.12 | 2.691E-10 | 0 | 41647 | gtex_brain_ba24 |
| rs2844698 | 6 | 30931245 | VARS2 | ENSG00000137411.12 | 4.723E-9 | 0 | 49263 | gtex_brain_ba24 |
| rs2854011 | 6 | 31311211 | VARS2 | ENSG00000137411.12 | 2.665E-7 | 0 | 429229 | gtex_brain_ba24 |
| rs2517580 | 6 | 30810056 | VARS2 | ENSG00000137411.12 | 2.013E-6 | 0 | -71926 | gtex_brain_putamen_basal |
| rs2535336 | 6 | 30810654 | VARS2 | ENSG00000137411.12 | 1.207E-6 | 0 | -71328 | gtex_brain_putamen_basal |
| rs2517579 | 6 | 30811164 | VARS2 | ENSG00000137411.12 | 2.012E-6 | 0 | -70818 | gtex_brain_putamen_basal |
| rs2535335 | 6 | 30812497 | VARS2 | ENSG00000137411.12 | 1.332E-6 | 0 | 69485 | gtex_brain_putamen_basal |
| rs2844663 | 6 | 30815951 | VARS2 | ENSG00000137411.12 | 1.207E-6 | 0 | 66031 | gtex_brain_putamen_basal |
| rs2844662 | 6 | 30817879 | VARS2 | ENSG00000137411.12 | 1.207E-6 | 0 | 64103 | gtex_brain_putamen_basal |
| rs2517575 | 6 | 30819465 | VARS2 | ENSG00000137411.12 | 1.207E-6 | 0 | 62517 | gtex_brain_putamen_basal |
| rs2535327 | 6 | 30826904 | VARS2 | ENSG00000137411.12 | 4.243E-7 | 0 | -55078 | gtex_brain_putamen_basal |
| rs2535326 | 6 | 30832063 | VARS2 | ENSG00000137411.12 | 1.207E-6 | 0 | -49919 | gtex_brain_putamen_basal |
| rs2844655 | 6 | 30837538 | VARS2 | ENSG00000137411.12 | 4.243E-7 | 0 | -44444 | gtex_brain_putamen_basal |
| rs2517573 | 6 | 30840147 | VARS2 | ENSG00000137411.12 | 1.208E-6 | 0 | -41835 | gtex_brain_putamen_basal |
| rs2535329 | 6 | 30842674 | VARS2 | ENSG00000137411.12 | 4.356E-7 | 0 | -39308 | gtex_brain_putamen_basal |
| rs1264334 | 6 | 30844260 | VARS2 | ENSG00000137411.12 | 1.207E-6 | 0 | -37722 | gtex_brain_putamen_basal |
| rs1264330 | 6 | 30846919 | VARS2 | ENSG00000137411.12 | 9.508E-7 | 0 | -35063 | gtex_brain_putamen_basal |
| rs885910 | 6 | 30849124 | VARS2 | ENSG00000137411.12 | 1.24E-6 | 0 | -32858 | gtex_brain_putamen_basal |
| rs1264328 | 6 | 30850142 | VARS2 | ENSG00000137411.12 | 8.852E-7 | 0 | -31840 | gtex_brain_putamen_basal |
| rs1264327 | 6 | 30850582 | VARS2 | ENSG00000137411.12 | 4.243E-7 | 0 | -31400 | gtex_brain_putamen_basal |
| rs1264323 | 6 | 30855907 | VARS2 | ENSG00000137411.12 | 9.018E-7 | 0 | -26075 | gtex_brain_putamen_basal |
| rs1049623 | 6 | 30864829 | VARS2 | ENSG00000137411.12 | 9.018E-7 | 0 | -17153 | gtex_brain_putamen_basal |
| rs1264315 | 6 | 30865058 | VARS2 | ENSG00000137411.12 | 2E-6 | 0 | -16924 | gtex_brain_putamen_basal |
| rs41266876 | 6 | 30884251 | VARS2 | ENSG00000137411.12 | 1.472E-7 | 0 | 2269 | gtex_brain_putamen_basal |
| rs9262291 | 6 | 30886015 | VARS2 | ENSG00000137411.12 | 8.482E-7 | 0 | 4033 | gtex_brain_putamen_basal |
| rs9281079 | 6 | 30891705 | VARS2 | ENSG00000137411.12 | 8.234E-7 | 0 | 9723 | gtex_brain_putamen_basal |
| rs2240804 | 6 | 30920890 | VARS2 | ENSG00000137411.12 | 5.526E-7 | 0 | 38908 | gtex_brain_putamen_basal |
| rs17189763 | 6 | 30923527 | VARS2 | ENSG00000137411.12 | 5.526E-7 | 0 | 41545 | gtex_brain_putamen_basal |
| rs9264904 | 6 | 31272553 | VARS2 | ENSG00000137411.12 | 7.804E-7 | 0 | 390571 | gtex_brain_putamen_basal |
Section II. Transcriptome annotation
General gene expression (GTEx)
Gene expression of temporal and spatial changes (BrainSpan)
Footnote:
SC: sub-cortical regions; SM: sensory-motor regions; FC: frontal cortex; and TP: temporal-parietal cortex
ST1: fetal (13 - 26 postconception weeks), ST2: early infancy to late childhood (4 months to 11 years), and ST3: adolescence to adulthood (13 - 23 years)
The bar shown representes the lower 25% and upper 25% of the expression distribution.
No co-expressed genes in brain regions
Section III. Gene Ontology annotation
| Molecular function | 去的术语 | Evidence | Neuro keywords | PubMed ID |
|---|---|---|---|---|
| GO:0000166 | nucleotide binding | IEA | - | |
| GO:0005524 | ATP binding | IEA | - | |
| GO:0004832 | valine-tRNA ligase activity | IEA | - | |
| GO:0016874 | ligase activity | IEA | - | |
| Biological process | 去的术语 | Evidence | Neuro keywords | PubMed ID |
| GO:0006438 | valyl-tRNA氨酰化 | IEA | - | |
| Cellular component | 去的术语 | Evidence | Neuro keywords | PubMed ID |
| GO:0005737 | cytoplasm | IEA | - | |
| GO:0005739 | mitochondrion | IEA | - |
Section V. Pathway annotation
| Pathway name | Pathway size | # SZGR 2.0 genes in pathway | Info |
|---|---|---|---|
| KEGG VALINE LEUCINE AND ISOLEUCINE BIOSYNTHESIS | 11 | 8 | All SZGR 2.0 genes in this pathway |
| KEGG AMINOACYL TRNA BIOSYNTHESIS | 41 | 33 | All SZGR 2.0 genes in this pathway |
| REACTOME MITOCHONDRIAL TRNA AMINOACYLATION | 21 | 17 | All SZGR 2.0 genes in this pathway |
| REACTOME TRNA AMINOACYLATION | 42 | 34 | All SZGR 2.0 genes in this pathway |
| RICKMAN TUMOR DIFFERENTIATED WELL VS POORLY UP | 236 | 139 | All SZGR 2.0 genes in this pathway |
| IVANOVA HEMATOPOIESIS EARLY PROGENITOR | 532 | 309 | All SZGR 2.0 genes in this pathway |
| GAVIN FOXP3 TARGETS CLUSTER P6 | 91 | 44 | All SZGR 2.0 genes in this pathway |
| ACEVEDO LIVER CANCER DN | 540 | 340 | All SZGR 2.0 genes in this pathway |
| LEE RECENT THYMIC EMIGRANT | 227 | 128 | All SZGR 2.0 genes in this pathway |