Pathway Human Homo sapiens

Signaling by NTRKs

R-HSA-166520 in Reactome release 97: under Signaling by Receptor Tyrosine Kinases, with 134 genes placed in it by the mapping files and 4 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-166520 (mouse), R-RNO-166520 (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-166520.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2007-12-11
Last updated: 2020-03-16
Events inside: 4, counted from the record
Also named: Signaling by Neurotrophin Receptors

Neurotrophins (NGF, BDNF, NTF3 and NTF4) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: NTRK (TRK) tyrosine kinase receptors (TRKA, TRKB, TRKC), which differ in their preferred neurotrophin ligand, and p75NTR death receptor, which interacts with all neurotrophins. Besides the nervous system, TRK receptors and p75NTR are expressed in a variety of other tissues. For review, please refer to Bibel and Barde 2000, Poo 2001, Lu et al. 2005, Skaper 2012, Park and Poo 2013.

NTRK receptors, NTRK1 (TRKA), NTRK2 (TRKB) and NTRK3 (TRKC) are receptor tyrosine kinases activated by ligand binding to their extracellular domain. Ligand binding induces receptor dimerization, followed by trans-autophosphorylation of dimerized receptors on conserved tyrosine residues in the cytoplasmic region. Phosphorylated tyrosines in the intracellular domain of the receptor serve as docking sites for adapter proteins, triggering downstream signaling cascades.

NTRK1 (TRKA) is the receptor for the nerve growth factor (NGF). NGF is primarily secreted by tissues that are innervated by sensory and sympathetic neurons. NTRK1 signaling promotes growth and survival of neurons during embryonic development and maintenance of neuronal cell integrity in adulthood (reviewed by Marlin and Li 2015).

Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NTF4, also known as NT-4) are two high affinity ligands for NTRK2 (TRKB). Neurotrophin-3 (NTF3, also known as NT-3) binds to NTRK2 with low affinity and may not be a physiologically relevant ligand. Nerve growth factor (NGF), a high affinity ligand for NTRK1, does not interact with NTRK2. NTRK2 signaling is implicated in neuronal development in both the peripheral (PNS) and central nervous system (CNS) and may play a role in long-term potentiation (LTP) and learning (reviewed by Minichiello 2009). NTRK2 may modify neuronal excitability and synaptic transmission by directly phosphorylating voltage gated channels (Rogalski et al. 2000).

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 134 genes in this human pathway; showing 101 to 134, 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
GenePTPRO	AuthorityHGNC:9678	Mapping file id5800 NCBI file	EvidenceIEA
GenePTPRS	AuthorityHGNC:9681	Mapping file id5802 NCBI file	EvidenceIEA
GeneRAC1	AuthorityHGNC:9801	Mapping file id5879 NCBI file	EvidenceIEA, TAS
GeneRALA	AuthorityHGNC:9839	Mapping file id5898 NCBI file	EvidenceIEA
GeneRALB	AuthorityHGNC:9840	Mapping file id5899 NCBI file	EvidenceIEA
GeneRALGDS	AuthorityHGNC:9842	Mapping file id5900 NCBI file	EvidenceIEA, TAS
GeneRAP1A	AuthorityHGNC:9855	Mapping file id5906 NCBI file	EvidenceIEA, TAS
GeneRAPGEF1	AuthorityHGNC:4568	Mapping file id2889 NCBI file	EvidenceIEA, TAS
GeneREST	AuthorityHGNC:9966	Mapping file id5978 NCBI file	EvidenceTAS
GeneRHOA	AuthorityHGNC:667	Mapping file id387 NCBI file	EvidenceTAS
GeneRIT1	AuthorityHGNC:10023	Mapping file id6016 NCBI file	EvidenceIEA
GeneRIT2	AuthorityHGNC:10017	Mapping file id6014 NCBI file	EvidenceIEA
GeneRPS6KA1	AuthorityHGNC:10430	Mapping file id6195 NCBI file	EvidenceTAS
GeneRPS6KA2	AuthorityHGNC:10431	Mapping file id6196 NCBI file	EvidenceTAS
GeneRPS6KA3	AuthorityHGNC:10432	Mapping file id6197 NCBI file	EvidenceTAS
GeneRPS6KA5	AuthorityHGNC:10434	Mapping file id9252 NCBI file	EvidenceTAS
GeneRRAD	AuthorityHGNC:10446	Mapping file id6236 NCBI file	EvidenceTAS
GeneSGK1	AuthorityHGNC:10810	Mapping file id6446 NCBI file	EvidenceTAS
GeneSH3GL2	AuthorityHGNC:10831	Mapping file id6456 NCBI file	EvidenceIEA, TAS
GeneSH3GL3	AuthorityHGNC:10832	Mapping file id6457 NCBI file	EvidenceIEA
GeneSHC1	AuthorityHGNC:10840	Mapping file id6464 NCBI file	EvidenceIEA, TAS
GeneSHC2	AuthorityHGNC:29869	Mapping file id25759 NCBI file	EvidenceIEA, TAS
GeneSHC3	AuthorityHGNC:18181	Mapping file id53358 NCBI file	EvidenceIEA, TAS
GeneSOS1	AuthorityHGNC:11187	Mapping file id6654 NCBI file	EvidenceIEA, TAS
GeneSRC	AuthorityHGNC:11283	Mapping file id6714 NCBI file	EvidenceIEA, TAS
GeneSRF	AuthorityHGNC:11291	Mapping file id6722 NCBI file	EvidenceIEA, TAS
GeneSTAT3	AuthorityHGNC:11364	Mapping file id6774 NCBI file	EvidenceIEA
GeneTCF12	AuthorityHGNC:11623	Mapping file id6938 NCBI file	EvidenceIEA, TAS
GeneTIAM1	AuthorityHGNC:11805	Mapping file id7074 NCBI file	EvidenceIEA
GeneTPH1	AuthorityHGNC:12008	Mapping file id7166 NCBI file	EvidenceTAS
GeneTRIB1	AuthorityHGNC:16891	Mapping file id10221 NCBI file	EvidenceTAS
GeneVGF	AuthorityHGNC:12684	Mapping file id7425 NCBI file	EvidenceTAS
GeneVRK3	AuthorityHGNC:18996	Mapping file id51231 NCBI file	EvidenceTAS
GeneYWHAB	AuthorityHGNC:12849	Mapping file id7529 NCBI file	EvidenceIEA, TAS

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

Signaling by Receptor Tyrosine KinasesR-HSA-9006934536 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.