Pathway Human Homo sapiens

Regulation of beta-cell development

R-HSA-186712 in Reactome release 97: under Developmental Biology, with 42 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-186712 (mouse), R-RNO-186712 (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-186712.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2008-06-30
Last updated: 2021-09-15
Events inside: 4, counted from the record

The normal development of the pancreas during gestation has been intensively investigated over the past decade especially in the mouse (Servitja and Ferrer 2004; Chakrabarti and Mirmira 2003). Studies of genetic defects associated with maturity onset diabetes of the young (MODY) has provided direct insight into these processes as they take place in humans (Fajans et al. 2001). During embryogenesis, committed epithelial cells from the early pancreatic buds differentiate into mature endocrine and exocrine cells. It is helpful to schematize this process into four consecutive cellular stages, to begin to describe the complex interplay of signal transduction pathways and transcriptional networks. The annotations here are by no means complete - factors in addition to the ones described here must be active, and even for the ones that are described, only key examples of their regulatory effects and interactions have been annotated.

It is also important to realize that in the human, unlike the mouse, cells of the different stages can be present simultaneously in the developing pancreas and the linear representation of these developmental events shown here is an over-simplification of the actual developmental process (e.g., Sarkar et al. 2008).

The first stage of this process involves the predifferentiated epithelial cells of the two pancreatic anlagen that arise from the definitive endoderm at approximately somite stages 11-15 and undergo budding from somite stages 20-22. This period corresponds to gestational days 8.75-9.5 in the mouse, and 26 in the human.

Pancreatic buds subsequently coalesce to form a single primitive gland, while concomitantly a ductal tree lined by highly proliferative epithelial cells is formed. A subset of such epithelial cells is thought to differentiate into either endocrine or acinar exocrine cells. A third cellular stage is defined by the endocrine-committed progenitors that selectively express the basic helix-loop-helix transcription factor NEUROG3. NEUROG3 is known to activate a complex transcriptional network that is essential for the specification of endocrine cells. Many transcription factors that are activated by NEUROG3 are also involved in islet-subtype cellular specification and in subsequent stages of differentiation of endocrine cells. This transient cellular stage thus leads to the generation of all known pancreatic endocrine cells, including insulin-producing beta-cells, and glucagon-producing alpha cells, the final stage of this schematic developmental process.

The diagram below summarizes interactions that take place between transcription factors and transcription factor target genes during these cellular stages, and shows cases where there is both functional evidence that a transcription factor is required for the target gene to be expressed, and biochemical evidence that this interaction is direct. We also describe instances where a signaling pathway is known to regulate a transcription factor gene in this process, even if the intervening signaling pathway is not fully understood.

Literature Reactome attaches

Global gene expression profiling and histochemical analysis of the developing human fetal pancreasDiabetologia, 2008, vol. 51, p. 285-97PubMed 18094957
Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the youngN Engl J Med, 2001, vol. 345, p. 971-80PubMed 11575290
Transcription factors direct the development and function of pancreatic beta cellsTrends Endocrinol Metab, 2003, vol. 14, p. 78-84PubMed 12591178
Transcriptional networks controlling pancreatic development and beta cell functionDiabetologia, 2004, vol. 47, p. 597-613PubMed 15298336

Reactome's record lists 10 orthologous events, R-RNO-186712 (Rattus norvegicus), R-MMU-186712 (Mus musculus) among the species this site serves, and 8 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Regulation of beta-cell development". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-186712 with StableID: R-HSA-186712.4 (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 42 genes in this human pathway; showing 1 to 42, 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
GeneAKT1	AuthorityHGNC:391	Mapping file id207 NCBI file	EvidenceTAS
GeneAKT2	AuthorityHGNC:392	Mapping file id208 NCBI file	EvidenceTAS
GeneAKT3	AuthorityHGNC:393	Mapping file id10000 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceIEA
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceIEA
GeneFGF10	AuthorityHGNC:3666	Mapping file id2255 NCBI file	EvidenceIEA
GeneFOXA2	AuthorityHGNC:5022	Mapping file id3170 NCBI file	EvidenceIEA
GeneFOXA3	AuthorityHGNC:5023	Mapping file id3171 NCBI file	EvidenceIEA
GeneFOXO1	AuthorityHGNC:3819	Mapping file id2308 NCBI file	EvidenceIEA, TAS
GeneGCK	AuthorityHGNC:4195	Mapping file id2645 NCBI file	EvidenceIEA
GeneHES1	AuthorityHGNC:5192	Mapping file id3280 NCBI file	EvidenceIEA
GeneHNF1A	AuthorityHGNC:11621	Mapping file id6927 NCBI file	EvidenceIEA
GeneHNF1B	AuthorityHGNC:11630	Mapping file id6928 NCBI file	EvidenceIEA
GeneHNF4A	AuthorityHGNC:5024	Mapping file id3172 NCBI file	EvidenceIEA
GeneHNF4G	AuthorityHGNC:5026	Mapping file id3174 NCBI file	EvidenceIEA
GeneIAPP	AuthorityHGNC:5329	Mapping file id3375 NCBI file	EvidenceIEA
GeneINS	AuthorityHGNC:6081	Mapping file id3630 NCBI file	EvidenceIEA
GeneINSM1	AuthorityHGNC:6090	Mapping file id3642 NCBI file	EvidenceTAS
GeneKAT2A	AuthorityHGNC:4201	Mapping file id2648 NCBI file	EvidenceIEA
GeneKAT2B	AuthorityHGNC:8638	Mapping file id8850 NCBI file	EvidenceIEA
GeneMAFA	AuthorityHGNC:23145	Mapping file id389692 NCBI file	EvidenceIEA
GeneMAML1	AuthorityHGNC:13632	Mapping file id9794 NCBI file	EvidenceIEA
GeneMAML2	AuthorityHGNC:16259	Mapping file id84441 NCBI file	EvidenceIEA
GeneMAML3	AuthorityHGNC:16272	Mapping file id55534 NCBI file	EvidenceIEA
GeneMAMLD1	AuthorityHGNC:2568	Mapping file id10046 NCBI file	EvidenceIEA
GeneNEUROD1	AuthorityHGNC:7762	Mapping file id4760 NCBI file	EvidenceIEA, TAS
GeneNEUROG3	AuthorityHGNC:13806	Mapping file id50674 NCBI file	EvidenceIEA, TAS
GeneNKX2-2	AuthorityHGNC:7835	Mapping file id4821 NCBI file	EvidenceIEA, TAS
GeneNKX6-1	AuthorityHGNC:7839	Mapping file id4825 NCBI file	EvidenceIEA
GeneNOTCH1	AuthorityHGNC:7881	Mapping file id4851 NCBI file	EvidenceIEA
GeneNR5A2	AuthorityHGNC:7984	Mapping file id2494 NCBI file	EvidenceIEA
GeneONECUT1	AuthorityHGNC:8138	Mapping file id3175 NCBI file	EvidenceIEA
GeneONECUT3	AuthorityHGNC:13399	Mapping file id390874 NCBI file	EvidenceIEA
GenePAX4	AuthorityHGNC:8618	Mapping file idENSG00000106331 Ensembl file	EvidenceTAS
GenePAX6	AuthorityHGNC:8620	Mapping file id5080 NCBI file	EvidenceIEA
GenePDX1	AuthorityHGNC:6107	Mapping file id3651 NCBI file	EvidenceIEA
GenePKLR	AuthorityHGNC:9020	Mapping file id5313 NCBI file	EvidenceIEA
GenePTF1A	AuthorityHGNC:23734	Mapping file id256297 NCBI file	EvidenceIEA
GeneRBPJ	AuthorityHGNC:5724	Mapping file id3516 NCBI file	EvidenceIEA
GeneRFX6	AuthorityHGNC:21478	Mapping file id222546 NCBI file	EvidenceIEA
GeneSLC2A2	AuthorityHGNC:11006	Mapping file id6514 NCBI file	EvidenceIEA
GeneSNW1	AuthorityHGNC:16696	Mapping file id22938 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

Developmental BiologyR-HSA-12667381,589 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.