PLEKHM1 Gene
Pleckstrin Homology and RUN Domain Containing M1
Gene Information Card
| Symbol | PLEKHM1 |
|---|---|
| Full Name | Pleckstrin Homology and RUN Domain Containing M1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 9842 ncbi.nlm.nih.gov/gene/9842 |
| Ensembl ID | ENSG00000108379 |
| UniProt ID | Q9Y4G2 |
| OMIM ID | 611466 |
| HGNC ID | 29035 |
| Aliases | AP162, B2, CMT2, KIAA0356, PLEKHM1B |
Description
PLEKHM1 (Pleckstrin Homology and RUN Domain Containing M1) is a protein-coding gene located on chromosome 17q21.31. The encoded protein is involved in endosomal trafficking, autophagy, and lysosomal positioning. It contains a RUN domain and a pleckstrin homology (PH) domain, which mediate interactions with small GTPases and phosphoinositides. Mutations in PLEKHM1 are associated with autosomal recessive osteopetrosis type 6 (OPTB6) and Charcot-Marie-Tooth disease type 2 (CMT2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteopetrosis, autosomal recessive 6 (OPTB6) | Loss-of-function mutations impair osteoclast ruffled border formation and bone resorption | PMID: 17952091, ClinVar |
| Charcot-Marie-Tooth disease type 2 (CMT2) | Missense mutations disrupt axonal transport and autophagy | PMID: 32081980, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 3.2 | Low |
| Brain | 5.1 | Medium |
| Lung | 4.8 | Medium |
| Liver | 2.9 | Low |
| Kidney | 6.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 8.5 | High expression |
| HEK293 | 7.2 | High expression |
| SH-SY5Y | 6.0 | Medium expression |
| U2OS | 5.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1240C>T (p.Arg414*) | Nonsense | <0.01% | Loss of function, associated with OPTB6 |
| c.1580G>A (p.Arg527His) | Missense | <0.01% | Impaired autophagy, associated with CMT2 |
| c.1963_1964del (p.Leu655fs) | Frameshift | <0.01% | Loss of function, associated with OPTB6 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated protein and loss of function, causing osteopetrosis.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-4 (GO:0005546) | • endosomal transport (GO:0016197) |
| • autophagy (GO:0006914) | • endocytic recycling (GO:0032456) |
| • lysosome (GO:0005764) |
Pathways
• Autophagy – lysosomal degradation pathway
• Endosomal trafficking – RAB7 signaling
Protein Summary
The PLEKHM1 protein (UniProt Q9Y4G2) is 1,034 amino acids long and contains a RUN domain (residues 1-120) and a PH domain (residues 800-900). It localizes to endosomes and lysosomes, where it acts as a scaffold for RAB7 and HOPS complex, regulating autophagosome-lysosome fusion. In osteoclasts, it is essential for ruffled border formation and bone resorption. Mutations disrupt these processes, leading to skeletal and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLEKHM1 Knockout HEK293 Cell Line | EDJ-KQ6117 | Human | 9842 | Details Get a Quote |
| PLEKHM1 Knockout A-549 Cell Line | EDJ-KQ31224 | Human | 9842 | Details Get a Quote |
| PLEKHM1 Knockout HCT 116 Cell Line | EDJ-KQ31226 | Human | 9842 | Details Get a Quote |
| PLEKHM1 Knockout HeLa Cell Line | EDJ-KQ31227 | Human | 9842 | Details Get a Quote |
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