AP3M1 Gene (Adaptor Related Protein Complex 3 Subunit Mu 1)
AP3M1: A key component of the AP-3 complex involved in protein trafficking and linked to Hermansky-Pudlak syndrome and neurological disorders.
Gene Information Card
| Symbol | AP3M1 |
|---|---|
| Full Name | Adaptor Related Protein Complex 3 Subunit Mu 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.2 |
| NCBI Gene ID | 26985 ncbi.nlm.nih.gov/gene/26985 |
| Ensembl ID | ENSG00000120071 |
| UniProt ID | Q9Y2T2 |
| OMIM ID | 610376 |
| HGNC ID | 568 |
| Aliases | AP47B, MGC16121, mu3A, AP-3 complex subunit mu-1 |
Description
AP3M1 encodes the mu-1 subunit of the heterotetrameric adaptor protein complex 3 (AP-3). The AP-3 complex plays a critical role in sorting cargo proteins from the trans-Golgi network and endosomes to lysosomes and lysosome-related organelles. AP3M1 specifically recognizes tyrosine-based sorting signals within the cytoplasmic tails of transmembrane proteins. Mutations in AP3M1 are associated with Hermansky-Pudlak syndrome type 10 (HPS10), characterized by oculocutaneous albinism, bleeding diathesis, and immunodeficiency. The gene is also implicated in neurological disorders due to its role in synaptic vesicle biogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hermansky-Pudlak syndrome 10 (HPS10) | Loss-of-function mutations in AP3M1 disrupt AP-3 complex assembly, impairing cargo sorting to lysosome-related organelles (melanosomes, platelet dense granules, cytotoxic granules). This leads to albinism, bleeding, and immunodeficiency. | ClinVar, OMIM |
| Epilepsy, early-onset, with or without developmental delay | Homozygous or compound heterozygous AP3M1 variants cause synaptic vesicle trafficking defects, leading to neuronal hyperexcitability and developmental delay. | ClinVar, OMIM |
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Disruption of AP-3-mediated endosomal trafficking affects neuronal development and function. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Spleen | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Embryonic kidney cells |
| SH-SY5Y | 14.8 | Neuroblastoma cells |
| HeLa | 8.9 | Cervical carcinoma cells |
| K562 | 6.5 | Leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.346C>T (p.Arg116*) | Nonsense | Rare | Loss of function; premature stop codon leads to nonsense-mediated decay |
| c.632G>A (p.Arg211Gln) | Missense | Rare | Impaired AP-3 complex assembly and cargo binding |
| c.1A>G (p.Met1?) | Start loss | Very rare | Loss of translation initiation; complete loss of function |
| c.1048_1049del (p.Leu350Glufs*12) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most AP3M1 mutations are loss-of-function, leading to reduced or absent protein, impaired AP-3 complex formation, and defective lysosomal trafficking. This is the primary mechanism in HPS10.
Gain of Function (GOF)
No gain-of-function mutations have been reported for AP3M1.
Dominant Negative (DN)
No dominant-negative mutations have been described; the disorder follows an autosomal recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
| • protein transport | • intracellular protein transport |
| • vesicle-mediated transport | • lysosomal transport |
| • signal transduction | • synaptic vesicle endocytosis |
| • protein binding | • clathrin adaptor activity |
Pathways
• Lysosome (KEGG: hsa04142)
• Endocytosis (KEGG: hsa04144)
• Synaptic vesicle cycle (KEGG: hsa04721)
• AP-3 complex-mediated transport (Reactome: R-HSA-432722)
Protein Summary
AP3M1 is a 418-amino acid protein (UniProt Q9Y2T2) that functions as the medium (mu) subunit of the AP-3 complex. It contains a longin domain and a mu homology domain, which mediate interactions with clathrin and cargo proteins. The protein is ubiquitously expressed, with highest levels in brain and testis. It is essential for sorting transmembrane proteins to lysosomes and lysosome-related organelles. Defects in AP3M1 disrupt melanosome biogenesis, platelet dense granule formation, and cytotoxic granule function, leading to the clinical features of HPS10.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AP3M1 Knockout HEK293 Cell Line | EDJ-KQ8635 | Human | 26985 | Details Get a Quote |
| AP3M1 Knockout A-549 Cell Line | EDJ-KQ34798 | Human | 26985 | Details Get a Quote |
| AP3M1 Knockout HCT 116 Cell Line | EDJ-KQ34799 | Human | 26985 | Details Get a Quote |
| AP3M1 Knockout HeLa Cell Line | EDJ-KQ34800 | Human | 26985 | Details Get a Quote |
