TMEM38B
Transmembrane Protein 38B: A Key Regulator of Intracellular Calcium Release
Gene Information Card
| Symbol | TMEM38B |
|---|---|
| Full Name | Transmembrane Protein 38B |
| Gene Type | Protein coding |
| Chromosomal Location | 9q31.2 |
| NCBI Gene ID | 55151 ncbi.nlm.nih.gov/gene/55151 |
| Ensembl ID | ENSG00000136872 |
| UniProt ID | Q9NVV0 |
| OMIM ID | 611236 |
| HGNC ID | 28530 |
| Aliases | TRIC-B, bA108K14.1 |
Description
TMEM38B encodes the trimeric intracellular cation channel type B (TRIC-B), a monovalent cation channel localized to the endoplasmic reticulum (ER) membrane. TRIC-B facilitates counter-ion movement during calcium release from the ER via inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), thereby maintaining ER calcium homeostasis. Loss-of-function mutations in TMEM38B cause autosomal recessive osteogenesis imperfecta type XIV, characterized by bone fragility, fractures, and dentinogenesis imperfecta.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteogenesis Imperfecta Type XIV (OI type XIV) | Loss-of-function mutations in TMEM38B impair TRIC-B channel activity, disrupting ER calcium release and leading to defective bone mineralization and collagen processing. | ClinVar, OMIM |
| Osteogenesis Imperfecta with Dentinogenesis Imperfecta | Same mechanism as OI type XIV; additional dental abnormalities due to defective dentin formation. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 3.2 | Low |
| Heart | 8.5 | Medium |
| Skeletal Muscle | 12.1 | Medium |
| Brain | 6.4 | Medium |
| Kidney | 7.8 | Medium |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.5 | High expression |
| HeLa | 7.2 | Moderate expression |
| K562 | 5.0 | Low expression |
| MCF7 | 6.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.507delA (p.Lys169Asnfs*2) | Frameshift deletion | Rare | Loss of function; premature stop codon |
| c.2T>C (p.Met1Thr) | Missense | Rare | Loss of function; disrupts translation initiation |
| c.296G>A (p.Arg99His) | Missense | Rare | Loss of function; impaired channel activity |
Mutation functional classification
Loss of Function (LOF)
Most reported TMEM38B mutations are loss-of-function, leading to reduced or absent TRIC-B channel activity, resulting in ER calcium overload and impaired bone formation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TMEM38B.
Dominant Negative (DN)
No dominant-negative mutations have been described for TMEM38B.
View complete mutation data：
Gene Ontology (GO)
| • monoatomic cation channel activity | • endoplasmic reticulum membrane |
| • calcium ion homeostasis | • intracellular calcium release |
| • bone mineralization |
Pathways
• Calcium signaling pathway
• Endoplasmic reticulum calcium homeostasis
Protein Summary
TMEM38B encodes TRIC-B, a 337-amino acid protein with three transmembrane domains. It forms homotrimeric channels that conduct monovalent cations (K+, Na+) across the ER membrane. TRIC-B is essential for efficient Ca2+ release from the ER by providing charge compensation. The protein is widely expressed, with highest levels in heart and skeletal muscle. Mutations in TMEM38B disrupt ER calcium dynamics, leading to osteogenesis imperfecta type XIV.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM38B Knockout HEK293 Cell Line | EDJ-KQ15763 | Human | 55151 | Details Get a Quote |
| TMEM38B Knockout A-549 Cell Line | EDJ-KQ48934 | Human | 55151 | Details Get a Quote |
| TMEM38B Knockout HCT 116 Cell Line | EDJ-KQ48935 | Human | 55151 | Details Get a Quote |
| TMEM38B Knockout HeLa Cell Line | EDJ-KQ48936 | Human | 55151 | Details Get a Quote |
