OSTM1: Osteopetrosis-Associated Transmembrane Protein 1
Essential regulator of osteoclast function and lysosomal acidification
Gene Information Card
| Symbol | OSTM1 |
|---|---|
| Full Name | Osteopetrosis Associated Transmembrane Protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 28962 ncbi.nlm.nih.gov/gene/28962 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | Q86WC4 |
| OMIM ID | 607649 |
| HGNC ID | 21652 |
| Aliases | GL, OPTB5, HSPC019 |
Description
OSTM1 encodes a transmembrane protein that is essential for osteoclast-mediated bone resorption. It functions as a subunit of the vacuolar H+-ATPase (V-ATPase) complex, required for lysosomal acidification and proper osteoclast activity. Loss-of-function mutations lead to severe autosomal recessive osteopetrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive osteopetrosis type 5 (OPTB5) | Loss of OSTM1 disrupts V-ATPase function, impairing lysosomal acidification and osteoclast bone resorption | ClinVar, OMIM |
| Osteopetrosis, infantile malignant | Biallelic OSTM1 mutations cause defective osteoclast activity, leading to dense but brittle bones | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 8.3 | Low |
| Lung | 6.1 | Low |
| Kidney | 5.4 | Low |
| Brain | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoclasts (primary) | 15.0 | High expression; key for function |
| THP-1 (monocyte) | 7.8 | Moderate |
| HEK293 | 5.2 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1070G>A (p.Arg357Gln) | Missense | Rare | Loss of function; associated with osteopetrosis |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein produced |
| c.1327C>T (p.Arg443*) | Nonsense | Rare | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most OSTM1 mutations are loss-of-function, leading to impaired V-ATPase assembly and lysosomal acidification.
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)
| • lysosome (GO:0005764) | • vacuolar proton-transporting V-type ATPase complex (GO:0016471) |
| • vacuolar transport (GO:0007034) | • bone resorption (GO:0045453) |
| • ion transport (GO:0006811) |
Pathways
• V-ATPase-mediated acidification (Reactome: R-HSA-1222556)
• Osteoclast differentiation (KEGG: hsa04380)
Protein Summary
OSTM1 is a 334-amino-acid transmembrane protein with a single transmembrane domain. It localizes to lysosomal membranes and interacts with the V-ATPase V0 subunit, stabilizing the complex and enabling proton transport. In osteoclasts, this acidification is critical for dissolving bone mineral. Mutations cause severe osteopetrosis due to failed bone resorption.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OSTM1 Knockout HEK293 Cell Line | EDJ-KQ8941 | Human | 28962 | Details Get a Quote |
| OSTM1 Knockout HeLa Cell Line | EDJ-KQ34071 | Human | 28962 | Details Get a Quote |
| OSTM1 Knockout A-549 Cell Line | EDJ-KQ35295 | Human | 28962 | Details Get a Quote |
| OSTM1 Knockout HCT 116 Cell Line | EDJ-KQ35296 | Human | 28962 | Details Get a Quote |
