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 2026-10-01 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 2026-10-01 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 101 to 157, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneRPL8	AuthorityHGNC:10368	Mapping file id6132 NCBI file	EvidenceIEA
GeneRPL9	AuthorityHGNC:10369	Mapping file id6133 NCBI file	EvidenceIEA
GeneRPLP0	AuthorityHGNC:10371	Mapping file id6175 NCBI file	EvidenceIEA
GeneRPLP1	AuthorityHGNC:10372	Mapping file id6176 NCBI file	EvidenceIEA
GeneRPLP2	AuthorityHGNC:10377	Mapping file id6181 NCBI file	EvidenceIEA
GeneRPS10	AuthorityHGNC:10383	Mapping file id6204 NCBI file	EvidenceIEA
GeneRPS11	AuthorityHGNC:10384	Mapping file id6205 NCBI file	EvidenceIEA
GeneRPS12	AuthorityHGNC:10385	Mapping file id6206 NCBI file	EvidenceIEA
GeneRPS13	AuthorityHGNC:10386	Mapping file id6207 NCBI file	EvidenceIEA
GeneRPS14	AuthorityHGNC:10387	Mapping file id6208 NCBI file	EvidenceIEA
GeneRPS15	AuthorityHGNC:10388	Mapping file id6209 NCBI file	EvidenceIEA
GeneRPS15A	AuthorityHGNC:10389	Mapping file id6210 NCBI file	EvidenceIEA
GeneRPS16	AuthorityHGNC:10396	Mapping file id6217 NCBI file	EvidenceIEA
GeneRPS17	AuthorityHGNC:10397	Mapping file id6218 NCBI file	EvidenceIEA
GeneRPS18	AuthorityHGNC:10401	Mapping file id6222 NCBI file	EvidenceIEA
GeneRPS19	AuthorityHGNC:10402	Mapping file id6223 NCBI file	EvidenceIEA
GeneRPS2	AuthorityHGNC:10404	Mapping file id6187 NCBI file	EvidenceIEA
GeneRPS20	AuthorityHGNC:10405	Mapping file id6224 NCBI file	EvidenceIEA
GeneRPS21	AuthorityHGNC:10409	Mapping file id6227 NCBI file	EvidenceIEA
GeneRPS23	AuthorityHGNC:10410	Mapping file id6228 NCBI file	EvidenceIEA
GeneRPS24	AuthorityHGNC:10411	Mapping file id6229 NCBI file	EvidenceIEA
GeneRPS25	AuthorityHGNC:10413	Mapping file id6230 NCBI file	EvidenceIEA
GeneRPS26	AuthorityHGNC:10414	Mapping file id6231 NCBI file	EvidenceIEA
GeneRPS27	AuthorityHGNC:10416	Mapping file id6232 NCBI file	EvidenceIEA
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA
GeneRPS27L	AuthorityHGNC:18476	Mapping file id51065 NCBI file	EvidenceIEA
GeneRPS28	AuthorityHGNC:10418	Mapping file id6234 NCBI file	EvidenceIEA
GeneRPS29	AuthorityHGNC:10419	Mapping file id6235 NCBI file	EvidenceIEA
GeneRPS3	AuthorityHGNC:10420	Mapping file id6188 NCBI file	EvidenceIEA
GeneRPS3A	AuthorityHGNC:10421	Mapping file id6189 NCBI file	EvidenceIEA
GeneRPS4X	AuthorityHGNC:10424	Mapping file id6191 NCBI file	EvidenceIEA
GeneRPS4Y1	AuthorityHGNC:10425	Mapping file id6192 NCBI file	EvidenceIEA
GeneRPS4Y2	AuthorityHGNC:18501	Mapping file id140032 NCBI file	EvidenceIEA
GeneRPS5	AuthorityHGNC:10426	Mapping file id6193 NCBI file	EvidenceIEA
GeneRPS6	AuthorityHGNC:10429	Mapping file id6194 NCBI file	EvidenceIEA
GeneRPS7	AuthorityHGNC:10440	Mapping file id6201 NCBI file	EvidenceIEA
GeneRPS8	AuthorityHGNC:10441	Mapping file id6202 NCBI file	EvidenceIEA
GeneRPS9	AuthorityHGNC:10442	Mapping file id6203 NCBI file	EvidenceIEA
GeneRPSA	AuthorityHGNC:6502	Mapping file id3921 NCBI file	EvidenceIEA
GeneRPTOR	AuthorityHGNC:30287	Mapping file id57521 NCBI file	EvidenceTAS
GeneRRAGA	AuthorityHGNC:16963	Mapping file id10670 NCBI file	EvidenceTAS
GeneRRAGB	AuthorityHGNC:19901	Mapping file id10325 NCBI file	EvidenceTAS
GeneRRAGC	AuthorityHGNC:19902	Mapping file id64121 NCBI file	EvidenceTAS
GeneRRAGD	AuthorityHGNC:19903	Mapping file id58528 NCBI file	EvidenceTAS
GeneSAMTOR	AuthorityHGNC:26475	Mapping file id154743 NCBI file	EvidenceTAS
GeneSEC13	AuthorityHGNC:10697	Mapping file id6396 NCBI file	EvidenceTAS
GeneSEH1L	AuthorityHGNC:30379	Mapping file id81929 NCBI file	EvidenceTAS
GeneSESN1	AuthorityHGNC:21595	Mapping file id27244 NCBI file	EvidenceTAS
GeneSESN2	AuthorityHGNC:20746	Mapping file id83667 NCBI file	EvidenceTAS
GeneSH3BP4	AuthorityHGNC:10826	Mapping file id23677 NCBI file	EvidenceTAS
GeneSLC38A9	AuthorityHGNC:26907	Mapping file id153129 NCBI file	EvidenceTAS
GeneSZT2	AuthorityHGNC:29040	Mapping file id23334 NCBI file	EvidenceTAS
GeneTCIRG1	AuthorityHGNC:11647	Mapping file id10312 NCBI file	EvidenceTAS
GeneTRIB3	AuthorityHGNC:16228	Mapping file id57761 NCBI file	EvidenceIEA
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceIEA
GeneWDR24	AuthorityHGNC:20852	Mapping file id84219 NCBI file	EvidenceTAS
GeneWDR59	AuthorityHGNC:25706	Mapping file id79726 NCBI file	EvidenceTAS

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.