Pathway Human Homo sapiens

Formation of the cornified envelope

R-HSA-6809371 in Reactome release 97: under Keratinization, with 129 genes placed in it by the mapping files and 0 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-6809371 (mouse), R-RNO-6809371 (rat). 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-6809371.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-09-19
Last updated: 2017-06-22
Events inside: 27, counted from the record

As keratinocytes progress towards the upper epidermis, they undergo a unique process of cell death termed cornification (Eckhart et al. 2013). This involves the crosslinking of keratinocyte proteins such as loricrin and involucrin by transglutaminases and the breakdown of the nucleus and other organelles by intracellular and secreted proteases (Eckhart et al. 2000, Denecker et al. 2008). This process is strictly regulated by the Ca2+ concentration gradient in the epidermis (Esholtz et al. 2014). Loricrin and involucrin are encoded in ‘Epidermal Differentiation Complex’ linked to a large number of genes encoding nonredundant components of the CE (Kypriotou et al. 2012, Niehues et al. 2016). Keratinocytes produce specialized proteins and lipids which are used to construct the cornified envelope (CE), a heavily crosslinked submembranous layer that confers rigidity to the upper epidermis, allows keratin filaments to attach to any location in the cell membrane (Kirfel et al. 2003) and acts as a water-impermeable barrier. The CE has two functional parts: covalently cross-linked proteins (10 nm thick) that comprise the backbone of the envelope and covalently linked lipids (5 nm thick) that coat the exterior (Eckert et al. 2005). Desmosomal components are crosslinked to the CE to form corneodesmosomes, which bind cornified cells together (Ishida-Yamamoto et al. 2011). Mature terminally differentiated cornified cells consist mostly of keratin filaments covalently attached to the CE embedded in lipid lamellae (Kalinin et al. 2002). The exact composition of the cornified envelope varies between epithelia (Steinert et al. 1998); the relative amino-acid composition of the proteins used may determine differential mechanical properties (Kartasova et al. 1996).

Literature Reactome attaches

The cornified envelope: a model of cell death in the skinNat. Rev. Mol. Cell Biol., 2005, vol. 6, p. 328-40PubMed 15803139

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 129 genes in this human pathway; showing 101 to 129, 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
GeneLIPM	AuthorityHGNC:23455	Mapping file id340654 NCBI file	EvidenceTAS
GeneLIPN	AuthorityHGNC:23452	Mapping file id643418 NCBI file	EvidenceTAS
GeneLORICRIN	AuthorityHGNC:6663	Mapping file id4014 NCBI file	EvidenceTAS
GenePCSK6	AuthorityHGNC:8569	Mapping file id5046 NCBI file	EvidenceTAS
GenePERP	AuthorityHGNC:17637	Mapping file id64065 NCBI file	EvidenceTAS
GenePI3	AuthorityHGNC:8947	Mapping file id5266 NCBI file	EvidenceTAS
GenePKP1	AuthorityHGNC:9023	Mapping file id5317 NCBI file	EvidenceTAS
GenePKP2	AuthorityHGNC:9024	Mapping file id5318 NCBI file	EvidenceTAS
GenePKP3	AuthorityHGNC:9025	Mapping file id11187 NCBI file	EvidenceTAS
GenePKP4	AuthorityHGNC:9026	Mapping file id8502 NCBI file	EvidenceTAS
GenePPL	AuthorityHGNC:9273	Mapping file id5493 NCBI file	EvidenceTAS
GenePRSS8	AuthorityHGNC:9491	Mapping file id5652 NCBI file	EvidenceTAS
GeneRPTN	AuthorityHGNC:26809	Mapping file id126638 NCBI file	EvidenceTAS
GeneSPINK5	AuthorityHGNC:15464	Mapping file id11005 NCBI file	EvidenceTAS
GeneSPINK6	AuthorityHGNC:29486	Mapping file id404203 NCBI file	EvidenceTAS
GeneSPINK9	AuthorityHGNC:32951	Mapping file id643394 NCBI file	EvidenceTAS
GeneSPRR1A	AuthorityHGNC:11259	Mapping file id6698 NCBI file	EvidenceTAS
GeneSPRR1B	AuthorityHGNC:11260	Mapping file id6699 NCBI file	EvidenceTAS
GeneSPRR2A	AuthorityHGNC:11261	Mapping file id6700 NCBI file	EvidenceTAS
GeneSPRR2B	AuthorityHGNC:11262	Mapping file id6701 NCBI file	EvidenceTAS
GeneSPRR2D	AuthorityHGNC:11264	Mapping file id6703 NCBI file	EvidenceTAS
GeneSPRR2E	AuthorityHGNC:11265	Mapping file id6704 NCBI file	EvidenceTAS
GeneSPRR2F	AuthorityHGNC:11266	Mapping file id6705 NCBI file	EvidenceTAS
GeneSPRR2G	AuthorityHGNC:11267	Mapping file id6706 NCBI file	EvidenceTAS
GeneSPRR3	AuthorityHGNC:11268	Mapping file id6707 NCBI file	EvidenceTAS
GeneST14	AuthorityHGNC:11344	Mapping file id6768 NCBI file	EvidenceIEA, TAS
GeneTCHH	AuthorityHGNC:11791	Mapping file id7062 NCBI file	EvidenceTAS
GeneTGM1	AuthorityHGNC:11777	Mapping file id7051 NCBI file	EvidenceTAS
GeneTGM5	AuthorityHGNC:11781	Mapping file id9333 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

KeratinizationR-HSA-6805567217 genes

Children

None: no pathway of this release's list names this one as a parent.

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.