Pathway Human Homo sapiens

HDMs demethylate histones

R-HSA-3214842 in Reactome release 97: under Chromatin modifying enzymes, with 50 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-3214842 (mouse), R-RNO-3214842 (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-3214842.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-06-10
Last updated: 2019-03-25
Events inside: 17, counted from the record

Histone lysine demethylases (KDMs) are able to reverse N-methylations of histones and probably other proteins. To date KDMs have been demonstrated to catalyse demethylation of N-epsilon methylated lysine residues. Biochemically there are two distinct groups of N-epsilon methylated lysine demethylases with different catalytic mechanisms, both of which result in methyl group oxidation to produce formaldhyde. KDM1A, formerly known as Lysine Specific Demethylase 1 (LSD1), belongs to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family. The KDM1A reaction mechanism requires a protonatable lysine epsilon-amine group, not available in trimethylated lysines, which consequently are not KDM1 substrates. Other KDMs belong to the Jumonji C (JmjC) -domain containing family. These are members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases, which are characterised by the presence of a double-stranded beta-helix core fold. They require 2-oxoglutarate (2OG) and molecular oxygen as co-substrates, producing, in addition to formaldehyde, succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lysines.

The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature.

In general, methylation at histone H3 lysine-5 (H3K4) and lysine-37 (H3K36), including di- and trimethylation at these sites, has been linked to actively transcribed genes (reviewed in Martin & Zhang 2005). In contrast, lysine-10 (H3K9) promoter methylation is considered a repressive mark for euchromatic genes and is also one of the landmark modifications associated with heterochromatin (Peters et al. 2002).

The first reported JmjC-containing demethylases were KDM2A/B (JHDM1A/B, FBXL11/10). These catalyse demethylation of histone H3 lysine-37 when mono- or di-methylated (H3K36Me1/2) (Tsukada et al. 2006). They were found to contain a JmjC catalytic domain, previously implicated in chromatin-dependent functions (Clissold & Ponting 2001). Subsequently, many other JmjC enzymes have been identified and discovered to have lysine demethylase activities with distinct methylation site and state specificities.

KDM3A/B (JHDM2A/B) are specific for mono or di-methylated lysine-10 on histone H3 (H3K9Me1/2) (Yamane et al. 2006, Kim et al. 2012). KDM4A-C (JMJD2A-C/JHDM3A-C) catalyse demethylation of di- or tri-methylated histone H3 at lysine-10 (H3K9Me2/3) (Cloos et al. 2006, Fodor et al. 2006), with a strong preference for Me3 (Whetstine et al. 2007). KDM4D (JMJD2D) also catalyses demethylation of H3K9Me2/3 (Whetstine et al. 2007). KDM4A-C (JHDM3A-C) can also catalyse demethylation of lysine-37 of histone H3 (H3K36Me2/3) (Klose et al. 2006). KDM5A-D (JARID1A-D) catalyses demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007). KDM6A and KDM6B (UTX/JMJD3) catalyse demethylation of di- or tri-methylated lysine-28 of histone H3 (H3K27Me2/3) (Agger et al. 2007, Cho et al. 2007, De Santra et al. 2007, Lan et al. 2007, Lee et al. 2007).

KDM7A (KIAA1718/JHDM1D) catalyses demethylation of mono- or di-methylated lysine-10 of histone H3 (H3K9Me1/2) and mono- and di-methylated lysine-28 of histone H3 (H3K27Me1/2) (Horton et al. 2010, Huang et al. 2010). PHF8 (JHDM1E) catalyses demethylation of mono- or di-methylated lysine-10 of histone H3 (H3K9Me1/2) and mono-methylated lysine-21 of histone H4 (H4K20Me1) (Loenarz et al. 2010, Horton et al. 2010, Feng et al. 2010, Kleine-Kohlbrecher et al. 2010, Fortschegger et al. 2010, Qi et al. 2010, Liu et al. 2010). PHF2 (JHDM1E) catalyses demethylation of mono- or di-methylated lysine-10 of histone H3 (H3K9Me1/2) (Wen et al, 2010, Baba et al. 2011). JMJD6 was initially characterized as an arginine demethylase that catalyses demethylation of mono or di methylated arginine 3 of histone H3 (H3R2Me1/2) and arginine 4 of histone H4 (H4R3Me1/2) (Chang et al. 2007) although it was subsequently also characterized as a lysine hydroxylase (Webby et al. 2009). N.B. The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature.

Literature Reactome attaches

The diverse functions of histone lysine methylationNat. Rev. Mol. Cell Biol., 2005, vol. 6, p. 838-49PubMed 16261189

Reactome's record lists 13 orthologous events, R-RNO-3214842 (Rattus norvegicus), R-MMU-3214842 (Mus musculus) among the species this site serves, and 11 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"HDMs demethylate histones". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-3214842 with StableID: R-HSA-3214842.5 (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 50 genes in this human pathway; showing 1 to 50, 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
GeneARID5B	AuthorityHGNC:17362	Mapping file id84159 NCBI file	EvidenceTAS
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceTAS
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceTAS
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceTAS
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceTAS
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceTAS
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceTAS
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceTAS
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceTAS
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceTAS
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceTAS
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceTAS
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceTAS
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceTAS
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceTAS
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceTAS
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceTAS
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceTAS
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceTAS
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceTAS
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceTAS
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceTAS
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceTAS
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceTAS
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceTAS
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceTAS
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceTAS
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceTAS
GeneJMJD6	AuthorityHGNC:19355	Mapping file id23210 NCBI file	EvidenceTAS
GeneKDM1A	AuthorityHGNC:29079	Mapping file id23028 NCBI file	EvidenceTAS
GeneKDM1B	AuthorityHGNC:21577	Mapping file id221656 NCBI file	EvidenceTAS
GeneKDM2A	AuthorityHGNC:13606	Mapping file id22992 NCBI file	EvidenceTAS
GeneKDM2B	AuthorityHGNC:13610	Mapping file id84678 NCBI file	EvidenceTAS
GeneKDM3A	AuthorityHGNC:20815	Mapping file id55818 NCBI file	EvidenceTAS
GeneKDM3B	AuthorityHGNC:1337	Mapping file id51780 NCBI file	EvidenceTAS
GeneKDM4A	AuthorityHGNC:22978	Mapping file id9682 NCBI file	EvidenceTAS
GeneKDM4B	AuthorityHGNC:29136	Mapping file id23030 NCBI file	EvidenceTAS
GeneKDM4C	AuthorityHGNC:17071	Mapping file id23081 NCBI file	EvidenceTAS
GeneKDM4D	AuthorityHGNC:25498	Mapping file id55693 NCBI file	EvidenceTAS
GeneKDM5A	AuthorityHGNC:9886	Mapping file id5927 NCBI file	EvidenceTAS
GeneKDM5B	AuthorityHGNC:18039	Mapping file id10765 NCBI file	EvidenceTAS
GeneKDM5C	AuthorityHGNC:11114	Mapping file id8242 NCBI file	EvidenceTAS
GeneKDM5D	AuthorityHGNC:11115	Mapping file id8284 NCBI file	EvidenceTAS
GeneKDM6A	AuthorityHGNC:12637	Mapping file id7403 NCBI file	EvidenceTAS
GeneKDM6B	AuthorityHGNC:29012	Mapping file id23135 NCBI file	EvidenceTAS
GeneKDM7A	AuthorityHGNC:22224	Mapping file id80853 NCBI file	EvidenceTAS
GenePHF2	AuthorityHGNC:8920	Mapping file id5253 NCBI file	EvidenceTAS
GenePHF8	AuthorityHGNC:20672	Mapping file id23133 NCBI file	EvidenceTAS
GeneRIOX2	AuthorityHGNC:19441	Mapping file id84864 NCBI file	EvidenceTAS
GeneUTY	AuthorityHGNC:12638	Mapping file id7404 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

Chromatin modifying enzymesR-HSA-3247509272 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.