GALNT14 (Polypeptide N-Acetylgalactosaminyltransferase 14): A Key Regulator of Mucin-Type O-Glycosylation in Cancer and Development
GALNT14 encodes a Golgi-resident enzyme that initiates mucin-type O-glycosylation, influencing tumor progression, apoptosis resistance, and developmental processes. Its expression patterns and genetic alterations are increasingly recognized as biomarkers and therapeutic targets in oncology.
Gene Information Card
| Symbol | GALNT14 |
|---|---|
| Full Name | Polypeptide N-acetylgalactosaminyltransferase 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 79623 ncbi.nlm.nih.gov/gene/79623 |
| Ensembl ID | ENSG00000158089 |
| UniProt ID | Q96FL9 |
| OMIM ID | 609240 |
| HGNC ID | 23242 |
| Aliases | GalNAc-T14, pp-GalNAc-T14, FLJ12691 |
Description
GALNT14 encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family. These enzymes catalyze the initial step in mucin-type O-linked protein glycosylation, transferring N-acetylgalactosamine (GalNAc) to serine and threonine residues on target proteins. This post-translational modification is crucial for protein stability, trafficking, and cell-cell interactions. GALNT14 is a type II transmembrane protein localized to the Golgi apparatus. It exhibits unique substrate specificity and is involved in the glycosylation of various proteins, including death receptors (e.g., DR4 and DR5), which links it to the regulation of apoptosis. Its expression is tightly regulated during development and is frequently dysregulated in various cancers, where it can act as either an oncogene or a tumor suppressor depending on the cellular context.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular Carcinoma (HCC) | GALNT14 expression is associated with tumor invasiveness and poor prognosis. It modulates the glycosylation of growth factor receptors and matrix metalloproteinases, promoting cell migration and invasion. High expression is linked to resistance to TRAIL-induced apoptosis. | Multiple studies show elevated GALNT14 mRNA and protein in HCC tissues compared to normal liver. High expression correlates with metastasis, recurrence, and reduced overall survival. Functional assays demonstrate that knockdown of GALNT14 reduces cell migration and invasion in vitro and in vivo. |
| Pancreatic Cancer | GALNT14 contributes to the malignant phenotype by altering the O-glycosylation of cell surface receptors, potentially affecting signaling pathways involved in proliferation and survival. It may also influence the tumor microenvironment. | Expression profiling and immunohistochemistry show upregulation of GALNT14 in pancreatic ductal adenocarcinoma. In vitro studies indicate that GALNT14 silencing inhibits cancer cell growth and colony formation. |
| Colorectal Cancer | GALNT14 expression is heterogeneous, with both tumor-suppressive and oncogenic roles reported depending on the stage and subtype. It may influence the Wnt signaling pathway through glycosylation of key components. | Some studies report decreased expression in tumors compared to normal tissue, correlating with poor differentiation. Other studies show increased expression in metastatic lesions. Functional data suggest a role in cell adhesion and migration. |
| Non-Small Cell Lung Cancer (NSCLC) | GALNT14 is involved in the regulation of apoptosis through the glycosylation of death receptors (DR4/DR5). High expression may confer resistance to TRAIL-based therapies. | Expression analysis shows that GALNT14 is frequently overexpressed in NSCLC cell lines and tissues. Preclinical studies demonstrate that high GALNT14 levels correlate with resistance to TRAIL-induced apoptosis, while knockdown sensitizes cells to TRAIL. |
| Ovarian Cancer | GALNT14 expression is associated with chemoresistance and poor clinical outcomes. It may modify the glycosylation of drug transporters or apoptotic regulators. | Gene expression profiling and clinical data analysis link high GALNT14 expression with resistance to platinum-based chemotherapy and shorter progression-free survival. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 20.3 | Medium |
| Colon | 18.7 | Medium |
| Stomach | 15.2 | Medium |
| Liver | 12.1 | Medium |
| Pancreas | 10.5 | Low |
| Lung | 8.4 | Low |
| Kidney | 7.9 | Low |
| Breast | 6.1 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | 25.4 | High expression; used as a model for HCC studies. |
| MCF7 (Breast) | 12.8 | Moderate expression; estrogen receptor positive. |
| A549 (Lung) | 15.6 | High expression; associated with TRAIL resistance. |
| PANC-1 (Pancreas) | 22.1 | High expression; aggressive pancreatic cancer cell line. |
| HeLa (Cervix) | 9.2 | Low to moderate expression. |
| K562 (Leukemia) | 3.1 | Low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1516G>A (p.Asp506Asn) | Missense | Rare (<0.1%) | Located in the catalytic domain; predicted to affect enzyme activity. Clinical significance is uncertain. |
| c.1042C>T (p.Arg348Trp) | Missense | Rare (<0.1%) | In the lectin domain; may affect substrate binding. Found in a single case of colorectal cancer. |
| c.1873_1874insA (p.Thr625AsnfsTer26) | Frameshift | Very rare | Predicted to result in a truncated, non-functional protein. Loss-of-function variant. |
| c.1A>G (p.Met1Val) | Start codon loss | Very rare | Predicted to prevent translation initiation, leading to complete loss of protein expression. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, such as frameshift or start codon loss, are rare in the general population but may contribute to disease susceptibility in specific contexts. Complete loss of GALNT14 activity could disrupt normal glycosylation patterns, potentially affecting developmental processes or increasing susceptibility to certain cancers.
Gain of Function (GOF)
Gain-of-function mutations are not well-characterized for GALNT14. However, gene amplification or transcriptional upregulation leading to increased protein expression is a common mechanism in cancer, effectively acting as a functional gain that promotes tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been described for GALNT14. As a monomeric enzyme, it is unlikely that a mutant protein would interfere with the function of the wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • polypeptide N-acetylgalactosaminyltransferase activity | • manganese ion binding |
| • Golgi apparatus | • integral component of membrane |
| • protein glycosylation | • O-glycan processing |
| • apoptotic process | • cell adhesion |
| • response to endoplasmic reticulum stress |
Pathways
• Mucin-type O-glycan biosynthesis
• O-linked glycosylation of proteins
• TRAIL signaling pathway (via DR4/DR5 glycosylation)
• Regulation of apoptosis
Protein Summary
The GALNT14 protein (UniProt Q96FL9) is a type II transmembrane protein consisting of 551 amino acids. It has a short N-terminal cytoplasmic tail, a single transmembrane domain, and a large C-terminal catalytic domain that faces the Golgi lumen. The catalytic domain contains a GT1 (glycosyltransferase 1) domain and a C-terminal lectin domain. The enzyme requires manganese ions (Mn2+) as a cofactor. It functions as a monomer and initiates mucin-type O-glycosylation by transferring GalNAc from UDP-GalNAc to serine or threonine residues on target proteins. Its substrate specificity is distinct from other GalNAc-Ts, with a preference for certain peptide sequences. The protein plays a critical role in modulating the function of its substrates, most notably the death receptors DR4 and DR5, thereby influencing cellular sensitivity to apoptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GALNT14 Knockout HEK293 Cell Line | EDJ-KQ13556 | Human | 79623 | Details Get a Quote |
| GALNT14 Knockout A-549 Cell Line | EDJ-KQ43186 | Human | 79623 | Details Get a Quote |
| GALNT14 Knockout HCT 116 Cell Line | EDJ-KQ43187 | Human | 79623 | Details Get a Quote |
| GALNT14 Knockout HeLa Cell Line | EDJ-KQ57193 | Human | 79623 | Details Get a Quote |
