Pathway Human Homo sapiens

Co-inhibition by PD-1

R-HSA-389948 in Reactome release 97: under Regulation of T cell activation by CD28 family, with 224 genes placed in it by the mapping files and 1 child pathway 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-389948 (mouse), R-RNO-389948 (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-389948.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2009-09-30
Last updated: 2020-09-24
Events inside: 6, counted from the record
Also named: PD-1 signaling

Programmed cell death protein 1 (PD-1) is a crucial inhibitory receptor that regulates T cell receptor (TCR) signaling and plays a vital role in maintaining immune homeostasis. PD-1 exerts its suppressive effects both directly, by inhibiting early activation events that are otherwise enhanced by co-stimulatory signals like CD28, and indirectly, by reducing interleukin-2 (IL-2) production, which is essential for T cell proliferation and survival. Upon ligation, PD-1 inhibits the expression of key survival and differentiation factors, such as Bcl-xL, and downregulates transcription factors that are central to effector T cell function, including GATA-3, T-bet, and Eomes. Mechanistically, PD-1 recruits the tyrosine phosphatases SHP-1 and SHP-2 to the immune synapse, leading to the dephosphorylation of critical signaling molecules like the CD3-zeta chain, PI3K, and AKT, thereby attenuating TCR signaling and inhibiting T cell activation and function (Keir et al. 2008).

Literature Reactome attaches

Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathwaysImmunol Rev, 2008, vol. 224, p. 166-82PubMed 18759926
PD-1 and its ligands in tolerance and immunityAnnu Rev Immunol, 2008, vol. 26, p. 677-704PubMed 18173375

Reactome's record lists 12 orthologous events, R-RNO-389948 (Rattus norvegicus), R-MMU-389948 (Mus musculus) among the species this site serves, and 10 in species this site opens no page for.

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 224 genes in this human pathway; showing 201 to 224, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 3 of 3
Gene	Authority id	Mapping file id	Evidence codes
GeneTCF7L1	AuthorityHGNC:11640	Mapping file id83439 NCBI file	EvidenceTAS
GeneTCF7L2	AuthorityHGNC:11641	Mapping file id6934 NCBI file	EvidenceTAS
GeneTEAD1	AuthorityHGNC:11714	Mapping file id7003 NCBI file	EvidenceTAS
GeneTEAD2	AuthorityHGNC:11715	Mapping file id8463 NCBI file	EvidenceTAS
GeneTEAD3	AuthorityHGNC:11716	Mapping file id7005 NCBI file	EvidenceTAS
GeneTEAD4	AuthorityHGNC:11717	Mapping file id7004 NCBI file	EvidenceTAS
GeneTMEM258	AuthorityHGNC:1164	Mapping file id746 NCBI file	EvidenceTAS
GeneTNRC6A	AuthorityHGNC:11969	Mapping file id27327 NCBI file	EvidenceTAS
GeneTNRC6B	AuthorityHGNC:29190	Mapping file id23112 NCBI file	EvidenceTAS
GeneTNRC6C	AuthorityHGNC:29318	Mapping file id57690 NCBI file	EvidenceTAS
GeneTRAV19	AuthorityHGNC:12115	Mapping file idENSG00000211799 Ensembl file	EvidenceTAS
GeneTRAV29DV5	AuthorityHGNC:12127	Mapping file idENSG00000211810 Ensembl file	EvidenceTAS
GeneTRAV8-4	AuthorityHGNC:12149	Mapping file idENSG00000211790 Ensembl file	EvidenceTAS
GeneTRBV12-3	AuthorityHGNC:12185	Mapping file idENSG00000274752 Ensembl file	EvidenceTAS
GeneTRBV7-9	AuthorityHGNC:12243	Mapping file idENSG00000278030 Ensembl file	EvidenceTAS
GeneTUSC3	AuthorityHGNC:30242	Mapping file id7991 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneVCP	AuthorityHGNC:12666	Mapping file id7415 NCBI file	EvidenceTAS
GeneWDR5	AuthorityHGNC:12757	Mapping file id11091 NCBI file	EvidenceTAS
GeneWWTR1	AuthorityHGNC:24042	Mapping file id25937 NCBI file	EvidenceTAS
GeneYAP1	AuthorityHGNC:16262	Mapping file id10413 NCBI file	EvidenceTAS
GeneYWHAG	AuthorityHGNC:12852	Mapping file id7532 NCBI file	EvidenceTAS

Evidence codes on this page: 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

Regulation of T cell activation by CD28 familyR-HSA-388841277 genes

Children

Regulation of PD-L1(CD274) expressionR-HSA-9909648199 genes

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.