Pathway Human Homo sapiens

Defective Intrinsic Pathway for Apoptosis

R-HSA-9734009 in Reactome release 97: under Diseases of programmed cell death, with 25 genes placed in it by the mapping files and 3 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; neither of the other two lists holds it. Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

Scripts are off

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-9734009.2
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: yes, as Reactome flags it
Released: 2021-09-15
Events inside: 3, counted from the record

Defects in the regulation of the intrinsic pathway for apoptosis are involved in diseases associated with increased cell loss, such as neurodegenerative diseases, as well as in diseases associated with impaired elimination of harmful cells, such as cancer and autoimmunity. For review, please refer to Reed 2001, Lavrik et al. 2009, and Tuzlak et al. 2016.

So far, Reactome has annotated apoptosis defects associated with the loss of function of the CDKN2A gene product p14ARF in cancer, loss of function of TP53 in cancer, and CDK5 dysregulation in neurodegenerative diseases.

Literature Reactome attaches

Apoptosis-regulating proteins as targets for drug discoveryTrends Mol Med, 2001, vol. 7, p. 314-9PubMed 11425640
Understanding apoptosis by systems biology approachesMol Biosyst, 2009, vol. 5, p. 1105-11PubMed 19756299
Interrogating the relevance of mitochondrial apoptosis for vertebrate development and postnatal tissue homeostasisGenes Dev, 2016, vol. 30, p. 2133-2151PubMed 27798841

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Defective Intrinsic Pathway for Apoptosis". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9734009 with StableID: R-HSA-9734009.2 (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 25 genes in this human pathway; showing 1 to 25, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneAPP	AuthorityHGNC:620	Mapping file id351 NCBI file	EvidenceTAS
GeneBCL2L11	AuthorityHGNC:994	Mapping file id10018 NCBI file	EvidenceTAS
GeneC1QBP	AuthorityHGNC:1243	Mapping file id708 NCBI file	EvidenceTAS
GeneCAPN1	AuthorityHGNC:1476	Mapping file id823 NCBI file	EvidenceIEA, TAS
GeneCAPN2	AuthorityHGNC:1479	Mapping file id824 NCBI file	EvidenceIEA, TAS
GeneCAPNS1	AuthorityHGNC:1481	Mapping file id826 NCBI file	EvidenceIEA, TAS
GeneCAPNS2	AuthorityHGNC:16371	Mapping file id84290 NCBI file	EvidenceIEA, TAS
GeneCAST	AuthorityHGNC:1515	Mapping file id831 NCBI file	EvidenceIEA, TAS
GeneCDC25A	AuthorityHGNC:1725	Mapping file id993 NCBI file	EvidenceTAS
GeneCDC25B	AuthorityHGNC:1726	Mapping file id994 NCBI file	EvidenceTAS
GeneCDC25C	AuthorityHGNC:1727	Mapping file id995 NCBI file	EvidenceTAS
GeneCDK5	AuthorityHGNC:1774	Mapping file id1020 NCBI file	EvidenceIEA, TAS
GeneCDK5R1	AuthorityHGNC:1775	Mapping file id8851 NCBI file	EvidenceIEA, TAS
GeneCDKN2A	AuthorityHGNC:1787	Mapping file id1029 NCBI file	EvidenceTAS
GeneFASLG	AuthorityHGNC:11936	Mapping file id356 NCBI file	EvidenceTAS
GeneFOXO3	AuthorityHGNC:3821	Mapping file id2309 NCBI file	EvidenceIEA, TAS
GeneGOLGA2	AuthorityHGNC:4425	Mapping file id2801 NCBI file	EvidenceIEA
GeneJUN	AuthorityHGNC:6204	Mapping file id3725 NCBI file	EvidenceIEA
GeneLMNA	AuthorityHGNC:6636	Mapping file id4000 NCBI file	EvidenceIEA
GeneLMNB1	AuthorityHGNC:6637	Mapping file id4001 NCBI file	EvidenceIEA
GenePRDX1	AuthorityHGNC:9352	Mapping file id5052 NCBI file	EvidenceIEA
GenePRDX2	AuthorityHGNC:9353	Mapping file id7001 NCBI file	EvidenceIEA
GeneSOD2	AuthorityHGNC:11180	Mapping file id6648 NCBI file	EvidenceTAS
GeneTP53	AuthorityHGNC:11998	Mapping file id7157 NCBI file	EvidenceTAS
GeneYWHAE	AuthorityHGNC:12851	Mapping file id7531 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

Diseases of programmed cell deathR-HSA-9645723108 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.