TMTC3: Transmembrane O-Mannosyltransferase Targeting Cadherins 3
A key regulator of protein O-mannosylation and cadherin-mediated cell adhesion, implicated in congenital disorders of glycosylation and cancer.
Gene Information Card
| Symbol | TMTC3 |
|---|---|
| Full Name | Transmembrane O-Mannosyltransferase Targeting Cadherins 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q21.31 |
| NCBI Gene ID | 160418 ncbi.nlm.nih.gov/gene/160418 |
| Ensembl ID | ENSG00000139329 |
| UniProt ID | Q6ZWK6 |
| OMIM ID | 617218 |
| HGNC ID | 25407 |
| Aliases | DKFZp686B10107, FLJ90079, MGC138290, MGC138291 |
Description
TMTC3 encodes a transmembrane protein localized to the endoplasmic reticulum that functions as an O-mannosyltransferase. It specifically transfers mannose to serine/threonine residues of cadherin family proteins, a post-translational modification critical for proper cadherin folding, trafficking, and cell-cell adhesion. Mutations in TMTC3 cause autosomal recessive intellectual disability with or without cerebellar ataxia (IDCA), a congenital disorder of glycosylation. Altered expression has been reported in several cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 63 (IDCA) | Loss-of-function mutations impair O-mannosylation of cadherins, disrupting neuronal adhesion and migration. | ClinVar, OMIM #617218 |
| Congenital disorder of glycosylation (TMTC3-CDG) | Deficient O-mannosylation leads to misfolding and retention of cadherins in the ER. | OMIM #617218 |
| Breast cancer | TMTC3 overexpression correlates with poor prognosis; may promote metastasis via altered cadherin glycosylation. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 4.1 | Low |
| Kidney | 6.7 | Low |
| Testis | 15.2 | Medium |
| Lung | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | Embryonic kidney cells; high expression |
| HeLa | 9.2 | Cervical cancer cells; moderate expression |
| MCF7 | 14.1 | Breast cancer cells; elevated expression |
| SH-SY5Y | 22.3 | Neuroblastoma cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.169C>T (p.Arg57*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1045G>A (p.Gly349Arg) | Missense | Rare | Loss of function; disrupts catalytic activity |
| c.1282C>T (p.Arg428Cys) | Missense | Rare | Loss of function; impairs ER localization |
| c.1552C>T (p.Arg518Trp) | Missense | Rare | Loss of function; reduces mannosyltransferase activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg57*, p.Gly349Arg) lead to loss of O-mannosyltransferase activity, causing cadherin hypoglycosylation and ER retention.
Gain of Function (GOF)
Not reported in TMTC3.
Dominant Negative (DN)
Not reported in TMTC3.
View complete mutation data：
Gene Ontology (GO)
| • mannosyltransferase activity (GO:0000030) | • endoplasmic reticulum (GO:0005783) |
| • integral component of membrane (GO:0016021) | • protein O-linked mannosylation (GO:0035269) |
| • extracellular matrix binding (GO:0050840) |
Pathways
• O-mannosylation of cadherins (R-HSA-5083635)
• Protein glycosylation (R-HSA-597592)
Protein Summary
TMTC3 is a 731-amino acid transmembrane protein with a conserved DXD motif essential for mannosyltransferase activity. It resides in the ER membrane and catalyzes the transfer of mannose from dolichol-phosphate-mannose to cadherin proteins. This O-mannosylation is required for cadherin stability, trafficking to the plasma membrane, and cell-cell adhesion. Loss of function leads to ER stress and impaired neuronal migration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMTC3 Knockout HEK293 Cell Line | EDJ-KQ15867 | Human | 160418 | Details Get a Quote |
| TMTC3 Knockout A-549 Cell Line | EDJ-KQ49080 | Human | 160418 | Details Get a Quote |
| TMTC3 Knockout HCT 116 Cell Line | EDJ-KQ49081 | Human | 160418 | Details Get a Quote |
| TMTC3 Knockout HeLa Cell Line | EDJ-KQ46862 | Human | 160418 | Details Get a Quote |
