MLPH Gene

Name	melanophilin
Description	This gene encodes a member of the exophilin subfamily of Rab effector proteins. The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein myosin Va. A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actin cytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin. A mutation in this gene results in Griscelli syndrome type 3, which is characterized by a silver-gray hair color and abnormal pigment distribution in the hair shaft. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMelanophilin (MLPH) is a key effector in pigment cell biology, functioning as a molecular adaptor that links the small GTPase Rab27A—bound to melanosome membranes—with the actin‐based motor protein myosin Va to mediate the transport of melanosomes toward the cell periphery. Structural studies have defined a conserved N‐terminal “Slp homology” or Rab-binding domain (sometimes termed RBD27) that is necessary and sufficient for the high affinity and GTP-dependent interaction with Rab27A, whereas distinct C-terminal regions engage with myosin Va and even directly interact with actin to capture melanosomes in peripheral actin networks. This tripartite complex, and its close homologues, thus enable the proper intracellular distribution of melanosomes in melanocytes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDisruption of MLPH function leads to pigmentary disorders. Mutations in the MLPH gene underlie Griscelli syndrome type III, a disorder characterized by hypopigmentation and abnormal clustering of melanosomes. Functional analyses have demonstrated that pathogenic variants impair MLPH’s ability to interact with Rab27A, resulting in perinuclear aggregation of melanosomes rather than their proper peripheral dispersion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in melanosome trafficking, MLPH has emerged as a candidate gene in oncogenesis and pigmentation-related risk. Genome-wide association studies have identified prostate cancer risk single-nucleotide polymorphisms within MLPH that upregulate specific transcript variants and correlate with tumor-suppressive activity. In parallel, variations in the 3′-untranslated region of MLPH have been associated with altered sun-sensitivity and melanoma predisposition. Furthermore, MLPH can be involved in oncogenic fusions, as evidenced by the recurrent MLPH-ALK fusion detected in pediatric Spitz nevi."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have also revealed a novel function for MLPH in adipocyte biology. Upregulated during adipogenesis in both murine and human cells, MLPH appears to be essential for maintaining redox homeostasis by preventing the excessive accumulation of reactive oxygen species and lipid peroxidation. Such a role implicates MLPH in broader metabolic processes and positions it as a potential modulator in metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mitsunori Fukuda, Taruho S Kuroda, Katsuhiko Mikoshiba "}, {"type": "b", "children": [{"type": "t", "text": "Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C200005200"}], "href": "https://doi.org/10.1074/jbc.C200005200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11856727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11856727"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Molly Strom, Alistair N Hume, Abul K Tarafder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M202574200"}], "href": "https://doi.org/10.1074/jbc.M202574200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11980908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11980908"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mitsunori Fukuda, Taruho S Kuroda "}, {"type": "b", "children": [{"type": "t", "text": "Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel linker protein that interacts with Rab27, myosin Va/VIIa, and actin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203862200"}], "href": "https://doi.org/10.1074/jbc.M203862200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12221080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12221080"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kazuaki Nagashima, Seiji Torii, Zhaohong Yi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(02)02634-0"}], "href": "https://doi.org/10.1016/s0014-5793(02"}, {"type": "t", "text": "02634-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12062444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12062444"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mitsunori Fukuda "}, {"type": "b", "children": [{"type": "t", "text": "Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a critical determinant of GTP-dependent specific binding to Rab27A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M205765200"}], "href": "https://doi.org/10.1074/jbc.M205765200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12189142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12189142"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gaël Ménasché, Chen Hsuan Ho, Ozden Sanal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI18264"}], "href": "https://doi.org/10.1172/JCI18264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12897212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12897212"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wendy Westbroek, Aharon Klar, Andrew R Cullinane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cellular and clinical report of new Griscelli syndrome type III cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pigment Cell Melanoma Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1755-148X.2011.00901.x"}], "href": "https://doi.org/10.1111/j.1755-148X.2011.00901.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21883982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21883982"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Morié Ishida, Saki P Arai, Norihiko Ohbayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in their cytosol: development of a novel melanosome-targetinG tag."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.552281"}], "href": "https://doi.org/10.1074/jbc.M114.552281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24584932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24584932"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Huajie Bu, Narisu Narisu, Bettina Schlick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22909"}], "href": "https://doi.org/10.1002/humu.22909"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26411452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26411452"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Catherine T Chung, Paula Marrano, David Swanson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2019.03.002"}], "href": "https://doi.org/10.1016/j.humpath.2019.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30857967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30857967"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Fankai Xiao, Peng Zhang, Yuan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single-nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.23127"}], "href": "https://doi.org/10.1002/mc.23127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31659808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31659808"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Barbara Hernando, Maria Peña-Chilet, Maider Ibarrola-Villava, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic 3'UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.13333"}], "href": "https://doi.org/10.1111/exd.13333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28266728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28266728"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Mi-Yeun Kim, Yang-Hyun Kim, Eun-Ran Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2024.150459"}], "href": "https://doi.org/10.1016/j.bbrc.2024.150459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39083977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39083977"}]}]}]}
Synonyms	SLAC2-A
Proteins	MELPH_HUMAN
NCBI Gene ID	79083
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MLPH has 10,501 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 125 datasets.

Click the + buttons to view associations for MLPH from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MLPH Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MLPH gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MLPH gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of MLPH gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MLPH gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MLPH gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MLPH gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MLPH gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MLPH gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of MLPH gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MLPH gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of MLPH gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MLPH protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MLPH gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MLPH gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MLPH gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of MLPH gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with MLPH gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MLPH gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of MLPH gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MLPH gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MLPH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MLPH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MLPH protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with MLPH protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing MLPH protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MLPH gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MLPH gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MLPH gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MLPH gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MLPH protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MLPH gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving MLPH gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MLPH gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MLPH gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MLPH gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with MLPH gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with MLPH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MLPH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MLPH gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MLPH gene from the ENCODE Transcription Factor Binding Site Profiles dataset.