Pathway Human Homo sapiens

MITF-M-regulated melanocyte development

R-HSA-9730414 in Reactome release 97: under Developmental Biology, with 160 genes placed in it by the mapping files and 2 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-9730414 (mouse), R-RNO-9730414 (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-9730414.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2024-03-27
Events inside: 2, counted from the record

Melanocyte Inducing Factor (MITF, also known as Microphthalmia-associated transcription factor) is a key regulator of melanocyte differentiation and development during embryogenesis, of differentiation of melanocyte stem cells post-natally, and of melanoma cells.

Melanocytes are cells that possess specialized organelles called melanosomes that synthesize eumelanin and pheomelanin from tyrosine in a series of reactions. Melanosomes are transferred from cutaneous melanocytes to adjacent keratinocytes to provide protection against UV as well as coloration of skin, eye, hair, feathers and scales. Besides being found in the basal layer of the skin, melanocytes are also present in hair follicles, the inner ear and in the iris eye, among other places. The eye also contains a layer of melanosome-containing cells behind the retina, called the retinal pigment epithelium (RPE) (reviewed in Mort et al, 2015; D'Mello et al, 2016; Goding and Arnheiter, 2019; Le et al, 2021; Cui and Man, 2023).

Cutaneous melanocytes and their precursors, melanoblasts, arise during embryogenesis from neural crest cells that migrate dorsolaterally through the developing embryo (reviewed in Mort et al, 2015). They also arise from glial/melanoblast precursors migrating on a ventromedial pathway and along nerves (Adameyko et al, 2009). Expression of MITF is a key determinant of melanocyte fate, and mutations in MITF are associated with a variety of defects in pigmentation as well as with deafness (due to absence of melanocytes in the inner ear) and microphthalmia (due to aberrant development of retina and RPE), among other conditions (reviewed in White and Zon, 2008; Mort et al, 2015; Goding and Arnheiter, 2019; Le et al, 2021).

The gene for MITF encodes several distinct isoforms based on alternative splicing. The gene has a 3' portion consisting of exons 2-9 that are generally shared by all transcripts. In mice and humans, the upstream region of the gene contains 9 exons, some of them coding, some not, and each regulated by its own promoter. Most of them are spliced to exon 2 via a common exon 1B. An exception is exon 1M which is directly spliced to exon 2, giving rise to the so-called M-isoform of MITF. This arrangement gives rise to a number of different mRNA and protein isoforms with preferential expression patterns. Exon 1A-containing transcripts, for instance, are ubiquitously expressed, exon 1H-containing transcripts are highly expressed in the heart, exon 1D-containing transcripts are expressed in the RPE, and exon 1M-containing transcripts are expressed in neural crest-derived melanocytes. Nevertheless, there is little information on whether the different isoforms have different functions except that exon 1B-containing transcripts (but not MITF-M) harbor a sequence subject to mTORC1 regulation (reviewed in Goding and Arnheiter, 2019; Vu et al, 2020). Most if not all transcripts come in two additional splice versions, one including and one excluding 18 bp of part of exon 6, called exon 6A, which encodes 6 amino acids lying upstream of the DNA-binding domain and which is regulated by MAPK signaling (Primot et al, 2010). They are usually referred to as the (+) and (-) versions of MITF. While the (-) version of a fragment of MITF-M has slightly reduced DNA-binding affinity compared to the (+) version, no specific role has so far been found for exon 6A (Pogenburg et al, 2012). Cell-based assays suggest that MITF (+) has a strong inhibitory effect on cellular proliferation relative to the (-) version, and MITF (-) is expressed at high levels in melanoma cells (Bismuth et al, 2005; Primot et al, 2010).

This pathway focuses on the activity of the melanocyte lineage-specific transcription factor MITF-M, although some of the biology described may also be relevant for other MITF isoforms.

Literature Reactome attaches

The melanocyte lineage in development and diseaseDevelopment, 2015, vol. 142, p. 620-32PubMed 25670789
Signaling Pathways in MelanogenesisInt J Mol Sci, 2016, vol. 17PubMed 27428965
MITF-the first 25 yearsGenes Dev, 2019, vol. 33, p. 983-1007PubMed 31123060
Melanosome Biogenesis in the Pigmentation of Mammalian SkinIntegr Comp Biol, 2021, vol. 61, p. 1517-1545PubMed 34021746
Biology of melanocytes in mammalsFront Cell Dev Biol, 2023, vol. 11, p. 1309557PubMed 38078014
Melanocytes in development, regeneration, and cancerCell Stem Cell, 2008, vol. 3, p. 242-52PubMed 18786412
Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skinCell, 2009, vol. 139, p. 366-79PubMed 19837037

Reactome's record lists 14 orthologous events, R-RNO-9730414 (Rattus norvegicus), R-MMU-9730414 (Mus musculus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"MITF-M-regulated melanocyte development". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9730414 with StableID: R-HSA-9730414.5 (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 160 genes in this human pathway; showing 101 to 160, 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
GenePLK1	AuthorityHGNC:9077	Mapping file id5347 NCBI file	EvidenceTAS
GenePMEL	AuthorityHGNC:10880	Mapping file id6490 NCBI file	EvidenceTAS
GenePOMC	AuthorityHGNC:9201	Mapping file id5443 NCBI file	EvidenceTAS
GenePOU3F2	AuthorityHGNC:9215	Mapping file id5454 NCBI file	EvidenceTAS
GenePPARGC1A	AuthorityHGNC:9237	Mapping file id10891 NCBI file	EvidenceTAS
GenePXDN	AuthorityHGNC:14966	Mapping file id7837 NCBI file	EvidenceTAS
GenePXN	AuthorityHGNC:9718	Mapping file id5829 NCBI file	EvidenceTAS
GeneQARS1	AuthorityHGNC:9751	Mapping file id5859 NCBI file	EvidenceTAS
GeneRAB27A	AuthorityHGNC:9766	Mapping file id5873 NCBI file	EvidenceTAS
GeneRARS1	AuthorityHGNC:9870	Mapping file id5917 NCBI file	EvidenceTAS
GeneRPS6KA1	AuthorityHGNC:10430	Mapping file id6195 NCBI file	EvidenceTAS
GeneSERPINE1	AuthorityHGNC:8583	Mapping file id5054 NCBI file	EvidenceTAS
GeneSIN3A	AuthorityHGNC:19353	Mapping file id25942 NCBI file	EvidenceTAS
GeneSIRT1	AuthorityHGNC:14929	Mapping file id23411 NCBI file	EvidenceTAS
GeneSMARCA2	AuthorityHGNC:11098	Mapping file id6595 NCBI file	EvidenceIEA, TAS
GeneSMARCA4	AuthorityHGNC:11100	Mapping file id6597 NCBI file	EvidenceIEA, TAS
GeneSMARCB1	AuthorityHGNC:11103	Mapping file id6598 NCBI file	EvidenceIEA, TAS
GeneSMARCC1	AuthorityHGNC:11104	Mapping file id6599 NCBI file	EvidenceIEA, TAS
GeneSMARCC2	AuthorityHGNC:11105	Mapping file id6601 NCBI file	EvidenceIEA, TAS
GeneSMARCD1	AuthorityHGNC:11106	Mapping file id6602 NCBI file	EvidenceIEA, TAS
GeneSMARCD2	AuthorityHGNC:11107	Mapping file id6603 NCBI file	EvidenceIEA, TAS
GeneSMARCD3	AuthorityHGNC:11108	Mapping file id6604 NCBI file	EvidenceIEA, TAS
GeneSMARCE1	AuthorityHGNC:11109	Mapping file id6605 NCBI file	EvidenceIEA, TAS
GeneSNAI2	AuthorityHGNC:11094	Mapping file id6591 NCBI file	EvidenceTAS
GeneSOX10	AuthorityHGNC:11190	Mapping file id6663 NCBI file	EvidenceTAS
GeneSOX2	AuthorityHGNC:11195	Mapping file id6657 NCBI file	EvidenceTAS
GeneSOX9	AuthorityHGNC:11204	Mapping file id6662 NCBI file	EvidenceTAS
GeneSS18	AuthorityHGNC:11340	Mapping file id6760 NCBI file	EvidenceIEA, TAS
GeneSS18L1	AuthorityHGNC:15592	Mapping file id26039 NCBI file	EvidenceIEA, TAS
GeneSTT3B	AuthorityHGNC:30611	Mapping file id201595 NCBI file	EvidenceTAS
GeneSUMO1	AuthorityHGNC:12502	Mapping file id7341 NCBI file	EvidenceTAS
GeneSYTL2	AuthorityHGNC:15585	Mapping file id54843 NCBI file	EvidenceTAS
GeneTBX2	AuthorityHGNC:11597	Mapping file id6909 NCBI file	EvidenceTAS
GeneTBX3	AuthorityHGNC:11602	Mapping file id6926 NCBI file	EvidenceTAS
GeneTCF7	AuthorityHGNC:11639	Mapping file id6932 NCBI file	EvidenceTAS
GeneTCF7L1	AuthorityHGNC:11640	Mapping file id83439 NCBI file	EvidenceTAS
GeneTCF7L2	AuthorityHGNC:11641	Mapping file id6934 NCBI file	EvidenceTAS
GeneTERT	AuthorityHGNC:11730	Mapping file id7015 NCBI file	EvidenceTAS
GeneTFAP2A	AuthorityHGNC:11742	Mapping file id7020 NCBI file	EvidenceTAS
GeneTFE3	AuthorityHGNC:11752	Mapping file id7030 NCBI file	EvidenceIEA
GeneTFEB	AuthorityHGNC:11753	Mapping file id7942 NCBI file	EvidenceIEA
GeneTFEC	AuthorityHGNC:11754	Mapping file id22797 NCBI file	EvidenceIEA
GeneTNFSF11	AuthorityHGNC:11926	Mapping file id8600 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
GeneTRPM1	AuthorityHGNC:7146	Mapping file id4308 NCBI file	EvidenceTAS
GeneTYR	AuthorityHGNC:12442	Mapping file id7299 NCBI file	EvidenceTAS
GeneTYRP1	AuthorityHGNC:12450	Mapping file id7306 NCBI file	EvidenceTAS
GeneUBE2I	AuthorityHGNC:12485	Mapping file id7329 NCBI file	EvidenceTAS
GeneUSF1	AuthorityHGNC:12593	Mapping file id7391 NCBI file	EvidenceTAS
GeneWNT3A	AuthorityHGNC:15983	Mapping file id89780 NCBI file	EvidenceTAS
GeneXPO1	AuthorityHGNC:12825	Mapping file id7514 NCBI file	EvidenceTAS
GeneYWHAB	AuthorityHGNC:12849	Mapping file id7529 NCBI file	EvidenceIEA
GeneYWHAE	AuthorityHGNC:12851	Mapping file id7531 NCBI file	EvidenceIEA
GeneYWHAG	AuthorityHGNC:12852	Mapping file id7532 NCBI file	EvidenceIEA
GeneYWHAH	AuthorityHGNC:12853	Mapping file id7533 NCBI file	EvidenceIEA
GeneYWHAZ	AuthorityHGNC:12855	Mapping file id7534 NCBI file	EvidenceIEA
GeneZEB1	AuthorityHGNC:11642	Mapping file id6935 NCBI file	EvidenceTAS
GeneZIC1	AuthorityHGNC:12872	Mapping file id7545 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

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.