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 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneACTB	AuthorityHGNC:132	Mapping file id60 NCBI file	EvidenceIEA, TAS
GeneACTL6A	AuthorityHGNC:24124	Mapping file id86 NCBI file	EvidenceIEA, TAS
GeneAGO1	AuthorityHGNC:3262	Mapping file id26523 NCBI file	EvidenceTAS
GeneAGO2	AuthorityHGNC:3263	Mapping file id27161 NCBI file	EvidenceTAS
GeneAGO3	AuthorityHGNC:18421	Mapping file id192669 NCBI file	EvidenceTAS
GeneAGO4	AuthorityHGNC:18424	Mapping file id192670 NCBI file	EvidenceTAS
GeneAIMP1	AuthorityHGNC:10648	Mapping file id9255 NCBI file	EvidenceTAS
GeneAIMP2	AuthorityHGNC:20609	Mapping file id7965 NCBI file	EvidenceTAS
GeneAKT2	AuthorityHGNC:392	Mapping file id208 NCBI file	EvidenceIEA
GeneAKT3	AuthorityHGNC:393	Mapping file id10000 NCBI file	EvidenceTAS
GeneALX3	AuthorityHGNC:449	Mapping file id257 NCBI file	EvidenceIEA, TAS
GeneARID1A	AuthorityHGNC:11110	Mapping file id8289 NCBI file	EvidenceIEA, TAS
GeneARID1B	AuthorityHGNC:18040	Mapping file id57492 NCBI file	EvidenceIEA, TAS
GeneASAH1	AuthorityHGNC:735	Mapping file id427 NCBI file	EvidenceTAS
GeneATP6AP2	AuthorityHGNC:18305	Mapping file idENSG00000182220 Ensembl file	EvidenceTAS
GeneATP6V0A1	AuthorityHGNC:865	Mapping file idENSG00000033627 Ensembl file	EvidenceTAS
GeneATP6V0B	AuthorityHGNC:861	Mapping file id533 NCBI file	EvidenceTAS
GeneATP6V0C	AuthorityHGNC:855	Mapping file id527 NCBI file	EvidenceTAS
GeneATP6V0D1	AuthorityHGNC:13724	Mapping file id9114 NCBI file	EvidenceTAS
GeneATP6V0E1	AuthorityHGNC:863	Mapping file id8992 NCBI file	EvidenceTAS
GeneATP6V0E2	AuthorityHGNC:21723	Mapping file idENSG00000171130 Ensembl file	EvidenceTAS
GeneATP6V1A	AuthorityHGNC:851	Mapping file id523 NCBI file	EvidenceTAS
GeneATP6V1B2	AuthorityHGNC:854	Mapping file id526 NCBI file	EvidenceTAS
GeneATP6V1C1	AuthorityHGNC:856	Mapping file id528 NCBI file	EvidenceTAS
GeneATP6V1D	AuthorityHGNC:13527	Mapping file idENSG00000100554 Ensembl file	EvidenceTAS
GeneATP6V1E1	AuthorityHGNC:857	Mapping file id529 NCBI file	EvidenceTAS
GeneATP6V1F	AuthorityHGNC:16832	Mapping file idENSG00000128524 Ensembl file	EvidenceTAS
GeneATP6V1G1	AuthorityHGNC:864	Mapping file id9550 NCBI file	EvidenceTAS
GeneATP6V1H	AuthorityHGNC:18303	Mapping file id51606 NCBI file	EvidenceTAS
GeneBCL2	AuthorityHGNC:990	Mapping file id596 NCBI file	EvidenceTAS
GeneBCL2A1	AuthorityHGNC:991	Mapping file id597 NCBI file	EvidenceTAS
GeneBCL7A	AuthorityHGNC:1004	Mapping file id605 NCBI file	EvidenceIEA, TAS
GeneBCL7B	AuthorityHGNC:1005	Mapping file id9275 NCBI file	EvidenceIEA, TAS
GeneBCL7C	AuthorityHGNC:1006	Mapping file id9274 NCBI file	EvidenceIEA, TAS
GeneBIRC7	AuthorityHGNC:13702	Mapping file id79444 NCBI file	EvidenceTAS
GeneBRCA1	AuthorityHGNC:1100	Mapping file id672 NCBI file	EvidenceTAS
GeneCCNB1	AuthorityHGNC:1579	Mapping file id891 NCBI file	EvidenceTAS
GeneCCND1	AuthorityHGNC:1582	Mapping file id595 NCBI file	EvidenceTAS
GeneCDC25B	AuthorityHGNC:1726	Mapping file id994 NCBI file	EvidenceTAS
GeneCDH1	AuthorityHGNC:1748	Mapping file id999 NCBI file	EvidenceTAS
GeneCDH2	AuthorityHGNC:1759	Mapping file id1000 NCBI file	EvidenceTAS
GeneCDK2	AuthorityHGNC:1771	Mapping file id1017 NCBI file	EvidenceTAS
GeneCDKN1A	AuthorityHGNC:1784	Mapping file id1026 NCBI file	EvidenceTAS
GeneCDKN2A	AuthorityHGNC:1787	Mapping file id1029 NCBI file	EvidenceTAS
GeneCEACAM1	AuthorityHGNC:1814	Mapping file id634 NCBI file	EvidenceTAS
GeneCREB1	AuthorityHGNC:2345	Mapping file id1385 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceIEA, TAS
GeneCSF1	AuthorityHGNC:2432	Mapping file id1435 NCBI file	EvidenceTAS
GeneCTNNB1	AuthorityHGNC:2514	Mapping file id1499 NCBI file	EvidenceTAS
GeneDARS1	AuthorityHGNC:2678	Mapping file id1615 NCBI file	EvidenceTAS
GeneDCT	AuthorityHGNC:2709	Mapping file id1638 NCBI file	EvidenceTAS
GeneDIAPH1	AuthorityHGNC:2876	Mapping file id1729 NCBI file	EvidenceTAS
GeneDICER1	AuthorityHGNC:17098	Mapping file id23405 NCBI file	EvidenceTAS
GeneDPF1	AuthorityHGNC:20225	Mapping file id8193 NCBI file	EvidenceIEA, TAS
GeneDPF2	AuthorityHGNC:9964	Mapping file id5977 NCBI file	EvidenceIEA, TAS
GeneDPF3	AuthorityHGNC:17427	Mapping file id8110 NCBI file	EvidenceIEA, TAS
GeneEDIL3	AuthorityHGNC:3173	Mapping file id10085 NCBI file	EvidenceTAS
GeneEDN1	AuthorityHGNC:3176	Mapping file id1906 NCBI file	EvidenceTAS
GeneEDN3	AuthorityHGNC:3178	Mapping file id1908 NCBI file	EvidenceTAS
GeneEDNRB	AuthorityHGNC:3180	Mapping file id1910 NCBI file	EvidenceTAS
GeneEEF1E1	AuthorityHGNC:3212	Mapping file id9521 NCBI file	EvidenceTAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceIEA, TAS
GeneEPRS1	AuthorityHGNC:3418	Mapping file id2058 NCBI file	EvidenceTAS
GeneFOXD3	AuthorityHGNC:3804	Mapping file id27022 NCBI file	EvidenceIEA, TAS
GeneGMPR	AuthorityHGNC:4376	Mapping file id2766 NCBI file	EvidenceTAS
GeneGPR143	AuthorityHGNC:20145	Mapping file id4935 NCBI file	EvidenceTAS
GeneGSK3B	AuthorityHGNC:4617	Mapping file id2932 NCBI file	EvidenceTAS
GeneGXYLT2	AuthorityHGNC:33383	Mapping file id727936 NCBI file	EvidenceTAS
GeneHDAC1	AuthorityHGNC:4852	Mapping file id3065 NCBI file	EvidenceTAS
GeneHINT1	AuthorityHGNC:4912	Mapping file id3094 NCBI file	EvidenceTAS
GeneIARS1	AuthorityHGNC:5330	Mapping file id3376 NCBI file	EvidenceTAS
GeneID1	AuthorityHGNC:5360	Mapping file id3397 NCBI file	EvidenceTAS
GeneIRF4	AuthorityHGNC:6119	Mapping file id3662 NCBI file	EvidenceTAS
GeneITGA2	AuthorityHGNC:6137	Mapping file id3673 NCBI file	EvidenceTAS
GeneKARS1	AuthorityHGNC:6215	Mapping file id3735 NCBI file	EvidenceTAS
GeneKIT	AuthorityHGNC:6342	Mapping file id3815 NCBI file	EvidenceTAS
GeneKITLG	AuthorityHGNC:6343	Mapping file id4254 NCBI file	EvidenceTAS
GeneLARS1	AuthorityHGNC:6512	Mapping file id51520 NCBI file	EvidenceTAS
GeneLEF1	AuthorityHGNC:6551	Mapping file id51176 NCBI file	EvidenceTAS
GeneLIG1	AuthorityHGNC:6598	Mapping file id3978 NCBI file	EvidenceTAS
GeneMAPK1	AuthorityHGNC:6871	Mapping file id5594 NCBI file	EvidenceTAS
GeneMAPK14	AuthorityHGNC:6876	Mapping file id1432 NCBI file	EvidenceTAS
GeneMAPK3	AuthorityHGNC:6877	Mapping file id5595 NCBI file	EvidenceTAS
GeneMARK3	AuthorityHGNC:6897	Mapping file id4140 NCBI file	EvidenceTAS
GeneMARS1	AuthorityHGNC:6898	Mapping file id4141 NCBI file	EvidenceTAS
GeneMC1R	AuthorityHGNC:6929	Mapping file id4157 NCBI file	EvidenceTAS
GeneMC3R	AuthorityHGNC:6931	Mapping file id4159 NCBI file	EvidenceTAS
GeneMC4R	AuthorityHGNC:6932	Mapping file id4160 NCBI file	EvidenceTAS
GeneMC5R	AuthorityHGNC:6933	Mapping file id4161 NCBI file	EvidenceTAS
GeneMCM2	AuthorityHGNC:6944	Mapping file id4171 NCBI file	EvidenceTAS
GeneMCM5	AuthorityHGNC:6948	Mapping file id4174 NCBI file	EvidenceTAS
GeneMET	AuthorityHGNC:7029	Mapping file id4233 NCBI file	EvidenceTAS
GeneMIR211	AuthorityHGNC:31588	Mapping file idENSG00000207702 Ensembl file	EvidenceTAS
GeneMITF	AuthorityHGNC:7105	Mapping file id4286 NCBI file	EvidenceIEA, TAS
GeneMLANA	AuthorityHGNC:7124	Mapping file id2315 NCBI file	EvidenceTAS
GeneMLPH	AuthorityHGNC:29643	Mapping file id79083 NCBI file	EvidenceTAS
GeneMOV10	AuthorityHGNC:7200	Mapping file id4343 NCBI file	EvidenceTAS
GeneMYO5A	AuthorityHGNC:7602	Mapping file id4644 NCBI file	EvidenceIEA, TAS
GeneMYRIP	AuthorityHGNC:19156	Mapping file id25924 NCBI file	EvidenceTAS
GenePAX3	AuthorityHGNC:8617	Mapping file id5077 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

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.