MLPH melanophilin [Homo sapiens (human)] - Gene

Summary

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

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion.
Title: RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-H98003 (e-PCR)
- UniSTS:20770

RH48487 (e-PCR)
- UniSTS:69925

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 more info	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

NG_007286.1 RefSeqGene

Range

4124..73032

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_83

mRNA and Protein(s)

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
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
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
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

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

237486410..237555322

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
XM_047445806.1 → XP_047301762.1 melanophilin isoform X2

UniProtKB/TrEMBL

A8KA64
XM_047445808.1 → XP_047301764.1 melanophilin isoform X8

UniProtKB/TrEMBL

A8KA64
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
XM_047445809.1 → XP_047301765.1 melanophilin isoform X9

UniProtKB/TrEMBL

A8KA64
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
XM_047445807.1 → XP_047301763.1 melanophilin isoform X4

UniProtKB/TrEMBL

A8KA64
XM_017004894.2 → XP_016860383.1 melanophilin isoform X7

UniProtKB/TrEMBL

A8KA64

Related

ENST00000468178.5
XM_047445810.1 → XP_047301766.1 melanophilin isoform X11
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
XM_047445811.1 → XP_047301767.1 melanophilin isoform X12

UniProtKB/TrEMBL

Q6UWC1
XM_047445812.1 → XP_047301768.1 melanophilin isoform X13

UniProtKB/TrEMBL

Q6UWC1
XM_047445813.1 → XP_047301769.1 melanophilin isoform X14

UniProtKB/TrEMBL

Q6UWC1