MLPH
protein-codingmelanophilin, the group of MicroRNA protein coding host genes
Gene 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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~69.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012220
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0012220
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0012220
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MLPH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024101.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 48 | 3 | 57 | ||
| missense | 2 | 103 | 28 | 3 | 136 | |
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 2 | 2 | 1 | 5 | ||
| splice donor/acceptor (+/-2bp) | 3 | 3 | 6 | |||
| Total | 4 | 8 | 113 | 76 | 6 | 207 |
Highest pathogenic variant AF is 0.000022306298
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_077006.1 | 15 | MANE Select | |
| Ensembl | ENSP00000264605.3 | 15 | MANE Select | |
| RefSeq | NP_001035932.1 | 14 | Standard | |
| RefSeq | NP_001268402.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mlpha | Danio rerio | Structure: melanocyte Quality: aggregated abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Deregulation of Rab and Rab Effector Genes in Bladder Cancer
Biological Process
- intracellular protein transport
- melanosome transport
Molecular Function
- actin binding
- protein binding
- myosin binding
- Rab GTPase binding
- protein binding, bridging
Cellular Component
- dendrite
- cortical actin cytoskeleton
- perinuclear region of cytoplasm
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264605
- Coding exons
- 15
- Length
- 69891
- Individuals with no LoFs
- 125702
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125748
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.124 | 347 | 341 | 1.02 | 0.0000215 | 3873 |
| Missense (PolyPhen) | 76 | 76.497 | 0.99351 | 889 | ||
| Synonymous | -0.104 | 148 | 146 | 1.01 | 0.0000101 | 1188 |
| Loss of Function | 2.00 | 20 | 32.3 | 0.619 | 0.00000175 | 383 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}.;
- Disease
- DISEASE: Griscelli syndrome 3 (GS3) [MIM:609227]: Rare autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes, without other clinical manifestations. {ECO:0000269|PubMed:12897212}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.185
Intolerance Scores
- LoFtool
- 0.808
- RVIS EVS
- 0.49
- RVIS percentile EVS
- 79.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.704
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |