Pathway Human Homo sapiens

MITF-M-dependent gene expression

R-HSA-9856651 in Reactome release 97: under MITF-M-regulated melanocyte development, with 109 genes placed in it by the mapping files and 8 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-9856651 (mouse), R-RNO-9856651 (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-9856651.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2024-03-27
Events inside: 8, counted from the record

MITF-M is a transcriptional regulator that is critical for the establishment of melanocyte fate during embryogenesis. Key targets include the enzymes responsible for the synthesis of the pigment compounds eumelanin and pheomelanin, as well as a number of structural components of the melanosome. In addition to regulating expression of genes involved in pigmentation, MITF has also been shown to play a role in the expression of genes involved in more diverse biological processes, including proliferation, survival, lysosome biogenesis, autophagy, metabolism, DNA damage, senescence and invasion (reviewed in Goding and Arnheiter, 2019; Mort et al, 2015; Zon and White, 2008, Cheli et al, 2010). Although widely characterized as a transcriptional activator, MITF-M has also be shown to act as a transcriptional repressor, negatively regulating the expression of genes involved in extracellular matrix organization, focal adhesion and epithelial-to-mesenchymal transition (Dilshat et al, 2021; reviewed in Rambow et al, 2019).

MITF is a basic helix loop helix leucine zipper (BHLH-ZIP)-containing protein and binds DNA as a dimer - either as a homodimer or as a heterodimer with the related transcription factors TFEB, TFE3, and TFEC. TFEB and TFE3 are both widely expressed, but TFEC displays more restricted expression. In this pathway, for simplicity, MITF is shown binding DNA exclusively as a homodimer (reviewed in Goding and Arnheiter, 2019).

MITF and related BHLH protein family members bind to an E-box-like element with sequence CANNTG. Specificity of binding is determined both by the flanking nucleotides and by the identity of the two internal nucleotides of the E-box element. MITF binds preferentially to sequences CATGTG or CACGTG, and binds with less affinity to the CAGCTG sequences preferred by other BHLH proteins such as AP4 (Lowing et al, 1992; Bentley et al, 1994; Yavuzer and Goding, 1994). High-affinity MITF-binding sites also show an enrichment for flanking 5'T and 3'A, further distinguishing these sites from those preferentially bound by transcription factors such as MYC and MAX (Aksan and Goding, 1998; Fisher et al, 1993; Solomon et al, 1993; Hejna et al, 2018). Variants of high-affinity MITF binding sites present in the promoters of pigmentation genes are called M-boxes, to distinguish them from related E-box sequences (reviewed in Goding and Arnheiter, 2019). Direct targets of MITF-M have been identified by ChIP-seq and CUT-and-RUN analysis in a number of primary and melanoma cell lines (Strub et al, 2011; Webster et al, 2014; Dilshat et al, 2021). In one of these studies, high-throughput ChIP-seq in the human melanoma cell line 501Mel identified MITF-binding at 5578 potential target genes, with 2771 showing promoter-proximal binding; only a subset of these genes were shown to be directly regulated by MITF, however (465; 240 down-regulated upon MITF knockdown, and 225 upregulated upon MITF overexpression) (Strub et al, 2001; reviewed in Goding and Arnheiter, 2019). MITF-bound genes included those involved in melanocyte biogenesis as well as DNA replication, repair and mitosis (Strub et al, 2011). Other studies have identified roles for MITF-M as a direct repressor of a number of genes implicated in estracellular matrix organization, cell adhesion, invasion and epithelial-to-mesenchymal transition (Laurette et al, 2015; Dilshat et al, 2021; reviewed Rambow et al, 2019).

Literature Reactome attaches

MITF-the first 25 yearsGenes Dev, 2019, vol. 33, p. 983-1007PubMed 31123060
The melanocyte lineage in development and diseaseDevelopment, 2015, vol. 142, p. 620-32PubMed 25670789
Melanocytes in development, regeneration, and cancerCell Stem Cell, 2008, vol. 3, p. 242-52PubMed 18786412
Fifteen-year quest for microphthalmia-associated transcription factor target genesPigment Cell Melanoma Res, 2010, vol. 23, p. 27-40PubMed 19995375
Positive and negative elements regulate a melanocyte-specific promoterMol Cell Biol, 1992, vol. 12, p. 3653-62PubMed 1321344
Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiatorMol Cell Biol, 1994, vol. 14, p. 7996-8006PubMed 7969139
Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSFMol Cell Biol, 1994, vol. 14, p. 3494-503PubMed 8164694

Reactome's record lists 10 orthologous events, R-MMU-9856651 (Mus musculus), R-RNO-9856651 (Rattus norvegicus) 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"MITF-M-dependent gene expression". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9856651 with StableID: R-HSA-9856651.3 (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 109 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
GeneAKT2	AuthorityHGNC:392	Mapping file id208 NCBI file	EvidenceIEA
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
GeneCTNNB1	AuthorityHGNC:2514	Mapping file id1499 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
GeneGMPR	AuthorityHGNC:4376	Mapping file id2766 NCBI file	EvidenceTAS
GeneGPR143	AuthorityHGNC:20145	Mapping file id4935 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
GeneIRF4	AuthorityHGNC:6119	Mapping file id3662 NCBI file	EvidenceTAS
GeneITGA2	AuthorityHGNC:6137	Mapping file id3673 NCBI file	EvidenceTAS
GeneLEF1	AuthorityHGNC:6551	Mapping file id51176 NCBI file	EvidenceTAS
GeneLIG1	AuthorityHGNC:6598	Mapping file id3978 NCBI file	EvidenceTAS
GeneMAPK14	AuthorityHGNC:6876	Mapping file id1432 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
GenePLK1	AuthorityHGNC:9077	Mapping file id5347 NCBI file	EvidenceTAS
GenePMEL	AuthorityHGNC:10880	Mapping file id6490 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
GeneRAB27A	AuthorityHGNC:9766	Mapping file id5873 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
GeneSOX10	AuthorityHGNC:11190	Mapping file id6663 NCBI file	EvidenceTAS
GeneSOX2	AuthorityHGNC:11195	Mapping file id6657 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
GeneSYTL2	AuthorityHGNC:15585	Mapping file id54843 NCBI file	EvidenceTAS
GeneTBX2	AuthorityHGNC:11597	Mapping file id6909 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

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

MITF-M-regulated melanocyte developmentR-HSA-9730414160 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.