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    MLPH melanophilin [ Homo sapiens (human) ]

    Gene ID: 79083, updated on 10-Dec-2024

    Summary

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    Official Symbol
    MLPHprovided by HGNC
    Official Full Name
    melanophilinprovided by HGNC
    Primary source
    HGNC:HGNC:29643
    See related
    Ensembl:ENSG00000115648 MIM:606526; AllianceGenome:HGNC:29643
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SLAC2-A
    Summary
    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]
    Expression
    Biased expression in stomach (RPKM 28.6), prostate (RPKM 26.5) and 12 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MLPH in Genome Data Viewer
    Location:
    2q37.3
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (237486410..237555322)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (237977449..238045300)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (238395053..238463965)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373954 Neighboring gene VISTA enhancer hs1951 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:238233151-238234350 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238242415-238242916 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238244426-238244926 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238244927-238245427 Neighboring gene collagen type VI alpha 3 chain Neighboring gene Sharpr-MPRA regulatory region 1020 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238275487-238275986 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238341552-238342058 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238354812-238355347 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238356546-238357046 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238357047-238357547 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238359577-238360252 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238360253-238360930 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17366 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:238368147-238369346 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12477 Neighboring gene uncharacterized LOC105373957 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238394761-238395729 Neighboring gene Sharpr-MPRA regulatory region 758 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238406043-238406543 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238419044-238419544 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238419545-238420045 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238421426-238421926 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238421927-238422427 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238428025-238428526 Neighboring gene microRNA 6811 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17367 Neighboring gene MT-ND5 pseudogene 46 Neighboring gene MT-ND4 pseudogene 40 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238450455-238450956 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:238472066-238472566 Neighboring gene RNA, U6 small nuclear 1140, pseudogene Neighboring gene prolactin releasing hormone

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. 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. Bu H, et al. Hum Mutat, 2016 Jan. PMID 26411452, Free PMC Article
    2. Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder. Lukusa T, et al. Genet Couns, 2004. PMID 15517821
    3. Single-nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4. Xiao F, et al. Mol Carcinog, 2020 Jan. PMID 31659808, Free PMC Article
    4. Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi. Chung CT, et al. Hum Pathol, 2019 May. PMID 30857967
    5. Cellular and clinical report of new Griscelli syndrome type III cases. Westbroek W, et al. Pigment Cell Melanoma Res, 2012 Jan. PMID 21883982, Free PMC Article

    See all (47) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes.
      Title: MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes.
    2. RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion.
      Title: RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion.
    3. This study provides strong evidence showing that prostate cancer risk Single-nucleotide polymorphism rs13426236 upregulates expression of MLPH transcript V4, which may function as a candidate oncogene in prostate cancer.
      Title: Single-nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4.
    4. Kinase fusions involving MYO5A and TPM3 have been reported in Spitz tumors, and our series adds MLPH to this group.
      Title: Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi.
    5. A novel Rab27a mutation binds melanophilin, but not Munc13-4, causing immunodeficiency without albinism.
      Title: A novel Rab27a mutation binds melanophilin, but not Munc13-4, causing immunodeficiency without albinism.
    6. we detected two potential associations with well-recognized skin cancer risk traits that modify miRNA-mRNA interactions: rs2325814 in the 3'UTR of the MLPH gene and rs752107 in the 3'UTR of the WNT3A gene.
      Title: Genetic 3'UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight.
    7. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH.
      Title: 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.
    8. The results showed that Rab27A(Q78L) is unable to localize on mature melanosomes and that its inhibitory activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin.
      Title: 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.
    9. The pathologic defect in Griscelli syndrome 3 came from the MLPH R35W substitution, which induced aggregation of melanosomes in the perinuclear area of melanocytes because of failure to interact with RAB27A.
      Title: Cellular and clinical report of new Griscelli syndrome type III cases.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: High throughput SNP and expression analyses of candidate genes for non-syndromic oral clefts.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Griscelli syndrome type 3
    MedGen: C1836573 OMIM: 609227 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies new prostate cancer susceptibility loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC2771, MGC59733

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables actin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables myosin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables myosin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-macromolecule adaptor activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in intracellular protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in melanosome transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cortical actin cytoskeleton IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in dendrite IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    melanophilin
    Names
    exophilin-3
    slp homolog lacking C2 domains a
    synaptotagmin-like protein 2a
    synaptotagmin-like protein homologue lacking C2 domains-a

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007286.1 RefSeqGene

      Range
      4124..73032
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_83

    mRNA and Protein(s)

    1. NM_001042467.3 → NP_001035932.1  melanophilin isoform 2

      See identical proteins and their annotated locations for NP_001035932.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC104667, BC014948, BC051269, BM992819, DC300186
      Consensus CDS
      CCDS42836.1
      UniProtKB/TrEMBL
      A8KA64
      Related
      ENSP00000341845.4, ENST00000338530.8
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:429 → 484
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    2. NM_001281473.2 → NP_001268402.1  melanophilin isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks three alternate in-frame exons compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC104667, AC112721, AK225381, BC014948, BM992819, DC300186
      Consensus CDS
      CCDS63173.1
      UniProtKB/TrEMBL
      A8KA64
      Related
      ENSP00000386780.1, ENST00000409373.5
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:359 → 392
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    3. NM_001281474.2 → NP_001268403.1  melanophilin isoform 4

      See identical proteins and their annotated locations for NP_001268403.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and lacks an alternate in-frame segment compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC104667, AC112721, AK094168, BC014948, BM992819
      Consensus CDS
      CCDS63172.1
      UniProtKB/Swiss-Prot
      Q9BV36
      Related
      ENSP00000386338.1, ENST00000410032.5
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:314 → 369
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    4. NM_024101.7 → NP_077006.1  melanophilin isoform 1

      See identical proteins and their annotated locations for NP_077006.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC104667, BC001653, BC014948, BM992819, DC300186
      Consensus CDS
      CCDS2518.1
      UniProtKB/Swiss-Prot
      B3KSS2, B4DKW7, G5E9G5, Q9BV36, Q9HA71
      UniProtKB/TrEMBL
      A8KA64
      Related
      ENSP00000264605.3, ENST00000264605.8
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:457 → 512
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    RNA

    1. NR_104019.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC104667, AK296745, BC014948, BM992819

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      237486410..237555322
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017004893.2 → XP_016860382.1  melanophilin isoform X1

      UniProtKB/TrEMBL
      A8KA64
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:457 → 512
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    2. XM_006712739.2 → XP_006712802.1  melanophilin isoform X5

      UniProtKB/TrEMBL
      A8KA64
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:427 → 460
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    3. XM_047445806.1 → XP_047301762.1  melanophilin isoform X2

      UniProtKB/TrEMBL
      A8KA64

    4. XM_047445808.1 → XP_047301764.1  melanophilin isoform X8

      UniProtKB/TrEMBL
      A8KA64

    5. XM_006712737.2 → XP_006712800.1  melanophilin isoform X3

      UniProtKB/TrEMBL
      A8KA64
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:417 → 472
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    6. XM_047445809.1 → XP_047301765.1  melanophilin isoform X9

      UniProtKB/TrEMBL
      A8KA64

    7. XM_006712740.2 → XP_006712803.1  melanophilin isoform X6

      UniProtKB/TrEMBL
      A8KA64
      Conserved Domains (2) summary
      pfam02318
      Location:8 → 125
      FYVE_2; FYVE-type zinc finger
      pfam04698
      Location:389 → 444
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    8. XM_047445807.1 → XP_047301763.1  melanophilin isoform X4

      UniProtKB/TrEMBL
      A8KA64

    9. XM_017004894.2 → XP_016860383.1  melanophilin isoform X7

      UniProtKB/TrEMBL
      A8KA64
      Related
      ENST00000468178.5

    10. XM_047445810.1 → XP_047301766.1  melanophilin isoform X11

    11. XM_011511812.2 → XP_011510114.1  melanophilin isoform X10

      UniProtKB/TrEMBL
      Q6UWC1
      Conserved Domains (1) summary
      pfam04698
      Location:312 → 367
      Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

    12. XM_047445811.1 → XP_047301767.1  melanophilin isoform X12

      UniProtKB/TrEMBL
      Q6UWC1

    13. XM_047445812.1 → XP_047301768.1  melanophilin isoform X13

      UniProtKB/TrEMBL
      Q6UWC1

    14. XM_047445813.1 → XP_047301769.1  melanophilin isoform X14

      UniProtKB/TrEMBL
      Q6UWC1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      237977449..238045300
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343851.1 → XP_054199826.1  melanophilin isoform X1

      UniProtKB/TrEMBL
      A8KA64

    2. XM_054343855.1 → XP_054199830.1  melanophilin isoform X5

      UniProtKB/TrEMBL
      A8KA64

    3. XM_054343852.1 → XP_054199827.1  melanophilin isoform X2

      UniProtKB/TrEMBL
      A8KA64

    4. XM_054343858.1 → XP_054199833.1  melanophilin isoform X8

      UniProtKB/TrEMBL
      A8KA64

    5. XM_054343853.1 → XP_054199828.1  melanophilin isoform X3

      UniProtKB/TrEMBL
      A8KA64

    6. XM_054343859.1 → XP_054199834.1  melanophilin isoform X9

      UniProtKB/TrEMBL
      A8KA64

    7. XM_054343856.1 → XP_054199831.1  melanophilin isoform X6

      UniProtKB/TrEMBL
      A8KA64

    8. XM_054343854.1 → XP_054199829.1  melanophilin isoform X4

      UniProtKB/TrEMBL
      A8KA64

    9. XM_054343857.1 → XP_054199832.1  melanophilin isoform X7

      UniProtKB/TrEMBL
      A8KA64

    10. XM_054343861.1 → XP_054199836.1  melanophilin isoform X11

    11. XM_054343860.1 → XP_054199835.1  melanophilin isoform X10

      UniProtKB/TrEMBL
      Q6UWC1

    12. XM_054343862.1 → XP_054199837.1  melanophilin isoform X12

      UniProtKB/TrEMBL
      Q6UWC1

    13. XM_054343863.1 → XP_054199838.1  melanophilin isoform X13

      UniProtKB/TrEMBL
      Q6UWC1

    14. XM_054343864.1 → XP_054199839.1  melanophilin isoform X14

      UniProtKB/TrEMBL
      Q6UWC1
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BV36.1 GenPept UniProtKB/Swiss-Prot:Q9BV36

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