TMTC2: Transmembrane O-Mannosyltransferase Targeting Cadherins 2
A key regulator of protein O-mannosylation and endoplasmic reticulum homeostasis
Gene Information Card
| Symbol | TMTC2 |
|---|---|
| Full Name | Transmembrane O-Mannosyltransferase Targeting Cadherins 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q21.31 |
| NCBI Gene ID | 160335 ncbi.nlm.nih.gov/gene/160335 |
| Ensembl ID | ENSG00000135447 |
| UniProt ID | Q8N394 |
| OMIM ID | 615856 |
| HGNC ID | 25410 |
| Aliases | DKFZp686B10107, FLJ90086, TMTC2A |
Description
TMTC2 encodes a transmembrane protein localized to the endoplasmic reticulum (ER) that functions as an O-mannosyltransferase. It specifically transfers mannose residues to cadherin and protocadherin proteins, a post-translational modification critical for proper protein folding, trafficking, and cell adhesion. TMTC2 is part of a family of four related proteins (TMTC1-4) and is implicated in ER stress response and calcium homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation (unspecified) | Impaired O-mannosylation of cadherins leads to ER retention and misfolding | PMID: 27595593 |
| Intellectual disability | Loss-of-function variants disrupt neuronal cadherin glycosylation | PMID: 31006510 |
| Autism spectrum disorder | Rare variants in TMTC2 identified in ASD cohorts | PMID: 25363760 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Testis | 10.8 | Medium |
| Heart | 8.5 | Low |
| Liver | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.4 | Neuronal model |
| HEK293 (embryonic kidney) | 9.7 | Common expression system |
| HepG2 (hepatocellular carcinoma) | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.187C>T (p.Arg63Trp) | Missense | 0.0002 | Reduced mannosyltransferase activity |
| c.1024G>A (p.Gly342Arg) | Missense | 0.0001 | ER retention of cadherins |
| c.1456_1457del (p.Leu486fs) | Frameshift | <0.0001 | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein and loss of enzymatic activity.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Missense variants may interfere with wild-type TMTC2 dimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• O-mannosylation of cadherins
• ER quality control and unfolded protein response
Protein Summary
TMTC2 is a 748-amino acid transmembrane protein with an N-terminal signal peptide, multiple transmembrane domains, and a C-terminal catalytic domain responsible for transferring mannose from dolichol-phosphate-mannose to serine/threonine residues of cadherin proteins. It localizes to the ER and is essential for proper cadherin folding and trafficking to the cell surface.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMTC2 Knockout HEK293 Cell Line | EDJ-KQ15866 | Human | 160335 | Details Get a Quote |
| TMTC2 Knockout A-549 Cell Line | EDJ-KQ49077 | Human | 160335 | Details Get a Quote |
| TMTC2 Knockout HCT 116 Cell Line | EDJ-KQ49078 | Human | 160335 | Details Get a Quote |
| TMTC2 Knockout HeLa Cell Line | EDJ-KQ49079 | Human | 160335 | Details Get a Quote |
