MLPH (Melanophilin)
Gene encoding a Rab effector protein involved in melanosome transport and pigmentation
Gene Information Card
| Symbol | MLPH |
|---|---|
| Full Name | Melanophilin |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 79083 ncbi.nlm.nih.gov/gene/79083 |
| Ensembl ID | ENSG00000115648 |
| UniProt ID | Q9BV36 |
| OMIM ID | 606526 |
| HGNC ID | 29643 |
| Aliases | Exophilin, Slac2-a, MGC:26692 |
Description
MLPH (melanophilin) encodes a Rab effector protein that functions as a linker between Rab27A on melanosomes and myosin Va, facilitating the transport of melanosomes along actin filaments within melanocytes. This process is essential for proper pigmentation of skin and hair. Mutations in MLPH cause Griscelli syndrome type 3, a rare autosomal recessive disorder characterized by hypopigmentation without immunological or neurological defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Griscelli syndrome type 3 | Loss-of-function mutations in MLPH disrupt melanosome transport, leading to pigment dilution in skin and hair | OMIM #609227; multiple case reports |
| Hypopigmentation (generalized) | Defective melanophilin impairs melanosome capture by actin filaments, reducing melanin transfer to keratinocytes | Functional studies in melanocyte models |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.3 | Medium |
| Thyroid | 5.1 | Low |
| Adipose tissue | 4.8 | Low |
| Brain (cerebellum) | 3.2 | Low |
| Testis | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Melanocytes | 15.2 | Highest expression; key for melanosome transport |
| SK-MEL-5 (melanoma) | 8.7 | Moderate expression |
| A375 (melanoma) | 6.4 | Moderate expression |
| HEK293 | 1.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.73C>T (p.Gln25*) | Nonsense | Rare | Premature stop; loss of function; associated with Griscelli syndrome type 3 |
| c.175C>T (p.Arg59*) | Nonsense | Rare | Premature stop; loss of function; Griscelli syndrome type 3 |
| c.400_401del (p.Leu134fs) | Frameshift | Rare | Frameshift leading to truncated protein; loss of function |
| c.571C>T (p.Arg191Trp) | Missense | Rare | Impaired binding to Rab27A; reduced melanosome transport |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that disrupt the Rab27A-binding or myosin Va-binding domains, leading to defective melanosome transport and hypopigmentation.
Gain of Function (GOF)
No gain-of-function mutations reported for MLPH.
Dominant Negative (DN)
No dominant-negative mutations reported; all known pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Melanosome transport pathway (Rab27A-MLPH-MyoVa)
• Pigmentation pathway
Protein Summary
Melanophilin (MLPH) is a 590-amino-acid protein that belongs to the exophilin family. It contains an N-terminal Rab27A-binding domain, a central myosin Va-binding domain, and a C-terminal actin-binding domain. By linking Rab27A-positive melanosomes to myosin Va, MLPH enables the capture and local movement of melanosomes at the actin cortex, a critical step for melanin transfer to keratinocytes. Loss of MLPH function results in pigment dilution, as seen in Griscelli syndrome type 3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MLPH Knockout HEK293 Cell Line | EDJ-KQ14274 | Human | 79083 | Details Get a Quote |
| MLPH Knockout A-549 Cell Line | EDJ-KQ44302 | Human | 79083 | Details Get a Quote |
| MLPH Knockout HCT 116 Cell Line | EDJ-KQ44303 | Human | 79083 | Details Get a Quote |
| MLPH Knockout HeLa Cell Line | EDJ-KQ57144 | Human | 79083 | Details Get a Quote |
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