TMEM63A: Transmembrane Protein 63A
A mechanosensitive ion channel implicated in neurological and developmental disorders
Gene Information Card
| Symbol | TMEM63A |
|---|---|
| Full Name | Transmembrane Protein 63A |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.12 |
| NCBI Gene ID | 9725 ncbi.nlm.nih.gov/gene/9725 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q9BVN2 |
| OMIM ID | 618686 |
| HGNC ID | 28618 |
| Aliases | C1orf172, FLJ10769, MGC131831 |
Description
TMEM63A encodes a transmembrane protein that functions as a mechanosensitive ion channel, permeable to calcium and other cations. It is involved in cellular responses to mechanical stimuli, including cell volume regulation and neuronal excitability. Mutations in TMEM63A are associated with autosomal dominant or recessive neurological disorders, including developmental and epileptic encephalopathy and hypomyelinating leukodystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy 89 (DEE89) | Loss-of-function mutations impair mechanosensitive channel activity, leading to altered neuronal excitability and synaptic dysfunction. | ClinVar, OMIM |
| Hypomyelinating leukodystrophy 24 (HLD24) | Biallelic loss-of-function mutations disrupt oligodendrocyte maturation and myelin formation. | ClinVar, OMIM |
| Autism spectrum disorder (ASD) | Rare missense variants may alter channel gating, contributing to neurodevelopmental phenotypes. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebellum | 15.2 | Medium |
| Spinal cord | 8.9 | Low |
| Heart | 6.3 | Low |
| Kidney | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.7 | High expression |
| U-87 MG (glioblastoma) | 14.2 | Medium expression |
| HEK 293 (embryonic kidney) | 9.5 | Low expression |
| HepG2 (hepatocellular carcinoma) | 3.8 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1282C>T (p.Arg428Trp) | Missense | Rare | Gain-of-function; increased channel activity linked to DEE89 |
| c.1015G>A (p.Gly339Arg) | Missense | Rare | Loss-of-function; reduced calcium influx associated with HLD24 |
| c.1546C>T (p.Arg516Ter) | Nonsense | Rare | Loss-of-function; premature truncation, likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift) cause hypomyelinating leukodystrophy 24 by impairing oligodendrocyte function.
Gain of Function (GOF)
Dominant missense mutations (e.g., p.Arg428Trp) increase channel open probability, leading to neuronal hyperexcitability and developmental epileptic encephalopathy.
Dominant Negative (DN)
Not reported for TMEM63A.
View complete mutation data：
Gene Ontology (GO)
| • mechanosensitive ion channel activity (GO:0008381) | • calcium channel activity (GO:0005262) |
| • calcium ion transport (GO:0006816) | • transmembrane transport (GO:0055085) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
Pathways
• Mechanotransduction pathway
• Calcium signaling pathway
Protein Summary
TMEM63A is a 810-amino acid transmembrane protein with multiple membrane-spanning domains. It forms a mechanosensitive ion channel that opens in response to membrane stretch, allowing calcium influx. The protein is highly expressed in the brain, particularly in neurons and oligodendrocytes, and plays a critical role in neuronal development, myelination, and cellular volume regulation. Structural studies suggest a pore-forming architecture similar to OSCA/TMEM63 family channels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM63A Knockout HEK293 Cell Line | EDJ-KQ6713 | Human | 9725 | Details Get a Quote |
| TMEM63A Knockout A-549 Cell Line | EDJ-KQ31079 | Human | 9725 | Details Get a Quote |
| TMEM63A Knockout HCT 116 Cell Line | EDJ-KQ31080 | Human | 9725 | Details Get a Quote |
| TMEM63A Knockout HeLa Cell Line | EDJ-KQ31081 | Human | 9725 | Details Get a Quote |
