TMCO1: Transmembrane and Coiled-Coil Domains 1
A key regulator of calcium homeostasis and craniofacial development
Gene Information Card
| Symbol | TMCO1 |
|---|---|
| Full Name | Transmembrane and Coiled-Coil Domains 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 54499 ncbi.nlm.nih.gov/gene/54499 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q9UM00 |
| OMIM ID | 614123 |
| HGNC ID | 29107 |
| Aliases | TMCO1, TMCC2, HSPC233, bA203I16.1 |
Description
TMCO1 encodes a transmembrane protein with coiled-coil domains that localizes to the endoplasmic reticulum (ER). It functions as a calcium leak channel, regulating ER calcium homeostasis. Mutations in TMCO1 cause TMCO1 deficiency syndrome, characterized by craniofacial anomalies, intellectual disability, and skeletal abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| TMCO1 deficiency syndrome (Cerebrofaciothoracic dysplasia) | Loss-of-function mutations impair ER calcium leak, leading to ER calcium overload and disrupted development | OMIM #213980; multiple case reports |
| Intellectual disability | Disrupted calcium signaling affects neuronal function and development | ClinVar; literature |
| Craniofacial anomalies | Impaired calcium homeostasis during embryogenesis | OMIM; case studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.8 | Low |
| Testis | 15.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Moderate expression |
| HeLa | 8.5 | Moderate expression |
| SH-SY5Y | 14.1 | Higher expression in neuronal cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | Rare | Loss of function; truncation |
| c.361_362del (p.Leu121fs) | Frameshift | Rare | Loss of function; premature stop |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein |
Mutation functional classification
Loss of Function (LOF)
Most TMCO1 mutations are loss-of-function, leading to reduced or absent protein, causing ER calcium overload and disease.
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)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Endoplasmic reticulum calcium homeostasis
Protein Summary
TMCO1 is a 238-amino acid transmembrane protein with two coiled-coil domains. It forms a homotetrameric calcium leak channel in the ER membrane, preventing calcium overload. Loss of function disrupts ER calcium homeostasis, leading to ER stress and developmental defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMCO1 Knockout HEK293 Cell Line | EDJ-KQ11442 | Human | 54499 | Details Get a Quote |
| TMCO1 Knockout A-549 Cell Line | EDJ-KQ39712 | Human | 54499 | Details Get a Quote |
| TMCO1 Knockout HCT 116 Cell Line | EDJ-KQ39713 | Human | 54499 | Details Get a Quote |
| TMCO1 Knockout HeLa Cell Line | EDJ-KQ39714 | Human | 54499 | Details Get a Quote |
