TMTC1: Transmembrane O-Mannosyltransferase Targeting Cadherins 1
A key regulator of cadherin glycosylation and potential tumor suppressor
Gene Information Card
| Symbol | TMTC1 |
|---|---|
| Full Name | Transmembrane O-Mannosyltransferase Targeting Cadherins 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p11.22 |
| NCBI Gene ID | 83857 ncbi.nlm.nih.gov/gene/83857 |
| Ensembl ID | ENSG00000111206 |
| UniProt ID | Q8IY22 |
| OMIM ID | 615857 |
| HGNC ID | 25419 |
| Aliases | DKFZp686P20110, FLJ32709, TMTC1A |
Description
TMTC1 encodes a transmembrane protein that functions as an O-mannosyltransferase, specifically adding O-mannose glycans to cadherin family proteins. This post-translational modification is critical for proper cadherin folding, trafficking, and cell-cell adhesion. TMTC1 is localized to the endoplasmic reticulum and is involved in the quality control of cadherins. Mutations and altered expression of TMTC1 have been implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of TMTC1 expression leads to reduced cadherin glycosylation, impairing cell adhesion and promoting metastasis. | PMID: 25691468 |
| Breast cancer | Downregulation of TMTC1 correlates with poor prognosis and increased invasiveness. | PMID: 30150673 |
| Intellectual disability | Homozygous missense mutations in TMTC1 disrupt O-mannosylation, affecting neuronal cadherins. | PMID: 28554332 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 4.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.5 | Embryonic kidney cells |
| HeLa | 7.8 | Cervical cancer cells |
| MCF7 | 5.2 | Breast cancer cells |
| HCT116 | 3.1 | Colorectal cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | 0.001% | Reduced enzyme activity; associated with intellectual disability |
| c.1672G>A (p.Gly558Arg) | Missense | 0.002% | Impaired cadherin glycosylation; reported in colorectal cancer |
| c.2140_2141del (p.Leu714fs) | Frameshift | <0.001% | Loss of function; observed in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein lacking catalytic activity, reducing cadherin O-mannosylation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations may produce a dominant-negative effect by dimerizing with wild-type TMTC1 and impairing its function.
View complete mutation data：
Gene Ontology (GO)
| • O-mannosyltransferase activity | • Endoplasmic reticulum membrane |
| • Protein O-linked mannosylation | • Cadherin binding |
| • Cell-cell adhesion |
Pathways
• O-mannosyl glycan biosynthesis
• Cadherin signaling pathway
Protein Summary
TMTC1 is a 714-amino acid transmembrane protein with a catalytic domain facing the ER lumen. It transfers mannose from dolichol-phosphate-mannose to serine/threonine residues of cadherin proteins. This modification is essential for cadherin stability and function in cell adhesion. TMTC1 is widely expressed, with highest levels in brain and testis. Loss of TMTC1 function disrupts cell adhesion and is linked to cancer progression and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMTC1 Knockout HEK293 Cell Line | EDJ-KQ2479 | Human | 83857 | Details Get a Quote |
| TMTC1 Knockout HeLa Cell Line | EDJ-KQ21693 | Human | 83857 | Details Get a Quote |
| TMTC1 Knockout A-549 Cell Line | EDJ-KQ65988 | Human | 83857 | Details Get a Quote |
| TMTC1 Knockout HCT 116 Cell Line | EDJ-KQ74412 | Human | 83857 | Details Get a Quote |
