Pathway Human Homo sapiens

Cellular response to starvation

R-HSA-9711097 in Reactome release 97: under Cellular responses to stress, with 157 genes placed in it by the mapping files and 2 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-9711097 (mouse), R-RNO-9711097 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9711097.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2021-03-23
Last updated: 2021-09-15
Events inside: 2, counted from the record

Deprivation of nutrients triggers diverse short- and long terms adaptations in cells. Here we have annotated two aspects of cellular responses to amino acid deprivation, ones mediated by EIF2AK4 and ones mediated by mTORC.

EIF2AK4 (GCN2) senses amino acid deficiency by binding uncharged tRNAs near the ribosome, and phosphorylating EIF2S1 (reviewed in Chaveroux et al. 2010, Castilho et al. 2014, Gallinetti et al. 2013, Bröer and Bröer 2017, Wek 2018). This reduces translation of most mRNAs but increases translation of mRNAs, notably ATF4, that mediate stress responses (reviewed in Kilberg et al. 2012, Wortel et al. 2017; Dever and Hinnebusch 2005).

The mTORC1 complex acts as an integrator that regulates translation, lipid synthesis, autophagy, and cell growth in response to multiple inputs, notably glucose, oxygen, amino acids, and growth factors such as insulin (reviewed in Sabatini 2017, Meng et al. 2018, Kim and Guan 2019).

MTOR, the kinase subunit of mTORC1, is activated by interaction with RHEB:GTP at the cytosolic face of lysosomal membrane (Long et al. 2005, Tee et al. 2005, Long et al. 2007, Yang et al. 2017). This process is regulated by various individual amino acids (reviewed in Zhuang et al. 2019, Wolfson and Sabatini 2017, Yao et al. 2017) and is reversed in response to the removal of amino acids, through the action of TSC1 (Demetriades et al. 2014).

Literature Reactome attaches

Amino acid homeostasis and signalling in mammalian cells and organismsBiochem. J., 2017, vol. 474, p. 1935-1963PubMed 28546457
Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TORBiochem. J., 2013, vol. 449, p. 1-10PubMed 23216249
GCN2 whets the appetite for amino acidsMol. Cell, 2005, vol. 18, p. 141-2PubMed 15837415
Keeping the eIF2 alpha kinase Gcn2 in checkBiochim. Biophys. Acta, 2014, vol. 1843, p. 1948-68PubMed 24732012
Molecular mechanisms involved in the adaptation to amino acid limitation in mammalsBiochimie, 2010, vol. 92, p. 736-45PubMed 20188139
Role of eIF2α Kinases in Translational Control and Adaptation to Cellular StressCold Spring Harb Perspect Biol, 2018, vol. 10PubMed 29440070
Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant CellsTrends Endocrinol. Metab., 2017, vol. 28, p. 794-806PubMed 28797581
The transcription factor network associated with the amino acid response in mammalian cellsAdv Nutr, 2012, vol. 3, p. 295-306PubMed 22585903
mTOR as a central hub of nutrient signalling and cell growthNat. Cell Biol., 2019, vol. 21, p. 63-71PubMed 30602761
Recent advances in understanding of amino acid signaling to mTORC1 activationFront Biosci (Landmark Ed), 2019, vol. 24, p. 971-982PubMed 30844724
The Dawn of the Age of Amino Acid Sensors for the mTORC1 PathwayCell Metab., 2017, vol. 26, p. 301-309PubMed 28768171
Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian CellsBiomolecules, 2017, vol. 7PubMed 28686218
Rheb binds and regulates the mTOR kinaseCurr Biol, 2005, vol. 15, p. 702-13PubMed 15854902
Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiencyJ. Biol. Chem., 2005, vol. 280, p. 23433-6PubMed 15878852
Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1FEBS Lett., 2005, vol. 579, p. 4763-8PubMed 16098514
The Rheb switch 2 segment is critical for signaling to target of rapamycin complex 1J. Biol. Chem., 2007, vol. 282, p. 18542-51PubMed 17470430
Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40Nature, 2017, vol. 552, p. 368-373PubMed 29236692
Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2Cell, 2014, vol. 156, p. 786-99PubMed 24529380
Twenty-five years of mTOR: Uncovering the link from nutrients to growthProc. Natl. Acad. Sci. U.S.A., 2017, vol. 114, p. 11818-11825PubMed 29078414
mTOR signaling in stem and progenitor cellsDevelopment, 2018, vol. 145PubMed 29311260

Reactome's record lists 13 orthologous events, R-RNO-9711097 (Rattus norvegicus), R-MMU-9711097 (Mus musculus) among the species this site serves, and 11 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Cellular response to starvation". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9711097 with StableID: R-HSA-9711097.5 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 157 genes in this human pathway; showing 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneASNS	AuthorityHGNC:753	Mapping file id440 NCBI file	EvidenceIEA
GeneATF2	AuthorityHGNC:784	Mapping file id1386 NCBI file	EvidenceIEA, TAS
GeneATF3	AuthorityHGNC:785	Mapping file id467 NCBI file	EvidenceIEA
GeneATF4	AuthorityHGNC:786	Mapping file id468 NCBI file	EvidenceIEA, TAS
GeneATP6V0B	AuthorityHGNC:861	Mapping file id533 NCBI file	EvidenceTAS
GeneATP6V0C	AuthorityHGNC:855	Mapping file id527 NCBI file	EvidenceTAS
GeneATP6V0D1	AuthorityHGNC:13724	Mapping file id9114 NCBI file	EvidenceTAS
GeneATP6V0D2	AuthorityHGNC:18266	Mapping file id245972 NCBI file	EvidenceTAS
GeneATP6V0E1	AuthorityHGNC:863	Mapping file id8992 NCBI file	EvidenceTAS
GeneATP6V0E2	AuthorityHGNC:21723	Mapping file id155066 NCBI file	EvidenceTAS
GeneATP6V1A	AuthorityHGNC:851	Mapping file id523 NCBI file	EvidenceTAS
GeneATP6V1B1	AuthorityHGNC:853	Mapping file id525 NCBI file	EvidenceTAS
GeneATP6V1B2	AuthorityHGNC:854	Mapping file id526 NCBI file	EvidenceTAS
GeneATP6V1C1	AuthorityHGNC:856	Mapping file id528 NCBI file	EvidenceTAS
GeneATP6V1C2	AuthorityHGNC:18264	Mapping file id245973 NCBI file	EvidenceTAS
GeneATP6V1D	AuthorityHGNC:13527	Mapping file id51382 NCBI file	EvidenceTAS
GeneATP6V1E1	AuthorityHGNC:857	Mapping file id529 NCBI file	EvidenceTAS
GeneATP6V1E2	AuthorityHGNC:18125	Mapping file id90423 NCBI file	EvidenceTAS
GeneATP6V1F	AuthorityHGNC:16832	Mapping file id9296 NCBI file	EvidenceTAS
GeneATP6V1G1	AuthorityHGNC:864	Mapping file id9550 NCBI file	EvidenceTAS
GeneATP6V1G2	AuthorityHGNC:862	Mapping file id534 NCBI file	EvidenceTAS
GeneATP6V1G3	AuthorityHGNC:18265	Mapping file id127124 NCBI file	EvidenceTAS
GeneATP6V1H	AuthorityHGNC:18303	Mapping file id51606 NCBI file	EvidenceTAS
GeneCASTOR1	AuthorityHGNC:34423	Mapping file id652968 NCBI file	EvidenceTAS
GeneCASTOR2	AuthorityHGNC:37073	Mapping file id729438 NCBI file	EvidenceTAS
GeneCEBPB	AuthorityHGNC:1834	Mapping file id1051 NCBI file	EvidenceIEA, TAS
GeneCEBPG	AuthorityHGNC:1837	Mapping file id1054 NCBI file	EvidenceIEA
GeneDDIT3	AuthorityHGNC:2726	Mapping file id1649 NCBI file	EvidenceIEA
GeneDEPDC5	AuthorityHGNC:18423	Mapping file id9681 NCBI file	EvidenceTAS
GeneEIF2AK4	AuthorityHGNC:19687	Mapping file id440275 NCBI file	EvidenceIEA
GeneEIF2S1	AuthorityHGNC:3265	Mapping file id1965 NCBI file	EvidenceIEA
GeneEIF2S2	AuthorityHGNC:3266	Mapping file id8894 NCBI file	EvidenceIEA
GeneEIF2S3	AuthorityHGNC:3267	Mapping file id1968 NCBI file	EvidenceIEA
GeneFAU	AuthorityHGNC:3597	Mapping file id2197 NCBI file	EvidenceIEA
GeneFLCN	AuthorityHGNC:27310	Mapping file id201163 NCBI file	EvidenceTAS
GeneFNIP1	AuthorityHGNC:29418	Mapping file id96459 NCBI file	EvidenceTAS
GeneFNIP2	AuthorityHGNC:29280	Mapping file id57600 NCBI file	EvidenceTAS
GeneGCN1	AuthorityHGNC:4199	Mapping file id10985 NCBI file	EvidenceIEA
GeneIMPACT	AuthorityHGNC:20387	Mapping file id55364 NCBI file	EvidenceIEA
GeneITFG2	AuthorityHGNC:30879	Mapping file id55846 NCBI file	EvidenceTAS
GeneKICS2	AuthorityHGNC:26517	Mapping file id144577 NCBI file	EvidenceTAS
GeneKPTN	AuthorityHGNC:6404	Mapping file id11133 NCBI file	EvidenceTAS
GeneLAMTOR1	AuthorityHGNC:26068	Mapping file id55004 NCBI file	EvidenceTAS
GeneLAMTOR2	AuthorityHGNC:29796	Mapping file id28956 NCBI file	EvidenceTAS
GeneLAMTOR3	AuthorityHGNC:15606	Mapping file id8649 NCBI file	EvidenceTAS
GeneLAMTOR4	AuthorityHGNC:33772	Mapping file id389541 NCBI file	EvidenceTAS
GeneLAMTOR5	AuthorityHGNC:17955	Mapping file id10542 NCBI file	EvidenceTAS
GeneMIOS	AuthorityHGNC:21905	Mapping file id54468 NCBI file	EvidenceTAS
GeneMLST8	AuthorityHGNC:24825	Mapping file id64223 NCBI file	EvidenceTAS
GeneMTOR	AuthorityHGNC:3942	Mapping file id2475 NCBI file	EvidenceTAS
GeneNPRL2	AuthorityHGNC:24969	Mapping file id10641 NCBI file	EvidenceTAS
GeneNPRL3	AuthorityHGNC:14124	Mapping file id8131 NCBI file	EvidenceTAS
GeneRHEB	AuthorityHGNC:10011	Mapping file id6009 NCBI file	EvidenceTAS
GeneRPL10	AuthorityHGNC:10298	Mapping file id6134 NCBI file	EvidenceIEA
GeneRPL10A	AuthorityHGNC:10299	Mapping file id4736 NCBI file	EvidenceIEA
GeneRPL10L	AuthorityHGNC:17976	Mapping file id140801 NCBI file	EvidenceIEA
GeneRPL11	AuthorityHGNC:10301	Mapping file id6135 NCBI file	EvidenceIEA
GeneRPL12	AuthorityHGNC:10302	Mapping file id6136 NCBI file	EvidenceIEA
GeneRPL13	AuthorityHGNC:10303	Mapping file id6137 NCBI file	EvidenceIEA
GeneRPL13A	AuthorityHGNC:10304	Mapping file id23521 NCBI file	EvidenceIEA
GeneRPL14	AuthorityHGNC:10305	Mapping file id9045 NCBI file	EvidenceIEA
GeneRPL15	AuthorityHGNC:10306	Mapping file id6138 NCBI file	EvidenceIEA
GeneRPL17	AuthorityHGNC:10307	Mapping file id6139 NCBI file	EvidenceIEA
GeneRPL18	AuthorityHGNC:10310	Mapping file id6141 NCBI file	EvidenceIEA
GeneRPL18A	AuthorityHGNC:10311	Mapping file id6142 NCBI file	EvidenceIEA
GeneRPL19	AuthorityHGNC:10312	Mapping file id6143 NCBI file	EvidenceIEA
GeneRPL21	AuthorityHGNC:10313	Mapping file id6144 NCBI file	EvidenceIEA
GeneRPL22	AuthorityHGNC:10315	Mapping file id6146 NCBI file	EvidenceIEA
GeneRPL22L1	AuthorityHGNC:27610	Mapping file id200916 NCBI file	EvidenceIEA
GeneRPL23	AuthorityHGNC:10316	Mapping file id9349 NCBI file	EvidenceIEA
GeneRPL23A	AuthorityHGNC:10317	Mapping file id6147 NCBI file	EvidenceIEA
GeneRPL24	AuthorityHGNC:10325	Mapping file id6152 NCBI file	EvidenceIEA
GeneRPL26	AuthorityHGNC:10327	Mapping file id6154 NCBI file	EvidenceIEA
GeneRPL26L1	AuthorityHGNC:17050	Mapping file id51121 NCBI file	EvidenceIEA
GeneRPL27	AuthorityHGNC:10328	Mapping file id6155 NCBI file	EvidenceIEA
GeneRPL27A	AuthorityHGNC:10329	Mapping file id6157 NCBI file	EvidenceIEA
GeneRPL28	AuthorityHGNC:10330	Mapping file id6158 NCBI file	EvidenceIEA
GeneRPL29	AuthorityHGNC:10331	Mapping file id6159 NCBI file	EvidenceIEA
GeneRPL3	AuthorityHGNC:10332	Mapping file id6122 NCBI file	EvidenceIEA
GeneRPL30	AuthorityHGNC:10333	Mapping file id6156 NCBI file	EvidenceIEA
GeneRPL31	AuthorityHGNC:10334	Mapping file id6160 NCBI file	EvidenceIEA
GeneRPL32	AuthorityHGNC:10336	Mapping file id6161 NCBI file	EvidenceIEA
GeneRPL34	AuthorityHGNC:10340	Mapping file id6164 NCBI file	EvidenceIEA
GeneRPL35	AuthorityHGNC:10344	Mapping file id11224 NCBI file	EvidenceIEA
GeneRPL35A	AuthorityHGNC:10345	Mapping file id6165 NCBI file	EvidenceIEA
GeneRPL36	AuthorityHGNC:13631	Mapping file id25873 NCBI file	EvidenceIEA
GeneRPL36A	AuthorityHGNC:10359	Mapping file id6173 NCBI file	EvidenceIEA
GeneRPL36AL	AuthorityHGNC:10346	Mapping file id6166 NCBI file	EvidenceIEA
GeneRPL37	AuthorityHGNC:10347	Mapping file id6167 NCBI file	EvidenceIEA
GeneRPL37A	AuthorityHGNC:10348	Mapping file id6168 NCBI file	EvidenceIEA
GeneRPL38	AuthorityHGNC:10349	Mapping file id6169 NCBI file	EvidenceIEA
GeneRPL39	AuthorityHGNC:10350	Mapping file id6170 NCBI file	EvidenceIEA
GeneRPL39L	AuthorityHGNC:17094	Mapping file id116832 NCBI file	EvidenceIEA
GeneRPL3L	AuthorityHGNC:10351	Mapping file id6123 NCBI file	EvidenceIEA
GeneRPL4	AuthorityHGNC:10353	Mapping file id6124 NCBI file	EvidenceIEA
GeneRPL41	AuthorityHGNC:10354	Mapping file id6171 NCBI file	EvidenceIEA
GeneRPL5	AuthorityHGNC:10360	Mapping file id6125 NCBI file	EvidenceIEA
GeneRPL6	AuthorityHGNC:10362	Mapping file id6128 NCBI file	EvidenceIEA
GeneRPL7	AuthorityHGNC:10363	Mapping file id6129 NCBI file	EvidenceIEA
GeneRPL7A	AuthorityHGNC:10364	Mapping file id6130 NCBI file	EvidenceIEA

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Cellular responses to stressR-HSA-2262752815 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.