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MLPH melanophilin [ Homo sapiens (human) ]

Gene ID: 79083, updated on 7-Apr-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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Location:
2q37.3
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (237486410..237555322)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (237977449..238045300)
105.20220307 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. 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
  2. Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi. Chung CT, et al. Hum Pathol, 2019 May. PMID 30857967
  3. 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
  4. Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder. Lukusa T, et al. Genet Couns, 2004. PMID 15517821
  5. RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion. Guo D, et al. J Invest Dermatol, 2020 Jul. PMID 31978414

See all (44) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion.
    Title: RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: High throughput SNP and expression analyses of candidate genes for non-syndromic oral clefts.
  10. links rab27a and myosin Va function in melanosome transport
    Title: A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport.
Submit: New GeneRIF Correction See all GeneRIFs (17)

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
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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)

Genotypes

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 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_2023_10

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

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

  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

  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

  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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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