GPA33: Glycoprotein A33, a Transmembrane Protein in Colorectal Cancer and Normal Intestinal Epithelium

Comprehensive gene card, expression, mutations, and clinical relevance of GPA33 (Glycoprotein A33) from NCBI, Ensembl, UniProt, OMIM, HGNC, COSMIC, and ClinVar.

Gene Information Card

Symbol GPA33
Full Name Glycoprotein A33 (transmembrane)
Gene Type protein-coding
Chromosomal Location 1q24.1
NCBI Gene ID 10223 ncbi.nlm.nih.gov/gene/10223
Ensembl ID ENSG00000143119
UniProt ID Q99795
OMIM ID 604414
HGNC ID 4450
Aliases A33, MGC125275, MGC125276

Description

GPA33 (Glycoprotein A33) encodes a cell surface transmembrane protein predominantly expressed in normal intestinal epithelium and in over 95% of colorectal cancers. The protein is a member of the immunoglobulin superfamily and is involved in cell–cell adhesion and intestinal epithelial homeostasis. Its restricted expression pattern makes it a target for antibody-based therapies in colorectal cancer.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Colorectal cancer Overexpression of GPA33 on tumor cells; used as a target for monoclonal antibody therapy (e.g., huA33) PMID: 10647931; NCBI Gene; UniProt
Gastric cancer Aberrant GPA33 expression reported in a subset of gastric adenocarcinomas PMID: 15625618; COSMIC
Inflammatory bowel disease (IBD) GPA33 expression is altered in inflamed intestinal epithelium, but direct mechanistic link is not fully established UniProt; literature review

Expression Profile

Tissue Expression
Tissue nTPM level
Colon 124.5 High
Small intestine 98.2 High
Rectum 87.3 High
Stomach 12.1 Low
Esophagus 5.6 Low
Liver 0.8 Not detected
Cell Line Expression
Cell Line nTPM Notes
Caco-2 (colorectal adenocarcinoma) 135.0 High expression; used in functional studies
HT-29 (colorectal adenocarcinoma) 112.4 High expression
SW480 (colorectal adenocarcinoma) 98.7 High expression
HCT 116 (colorectal carcinoma) 85.3 Moderate expression
MCF7 (breast cancer) 0.5 Not detected
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.497G>A (p.Arg166His) Missense 0.02% (COSMIC v99) Substitution in extracellular domain; functional impact unknown
c.1045C>T (p.Arg349Trp) Missense 0.01% (COSMIC v99) Located in cytoplasmic tail; may affect signaling
c.1234_1235insA (p.Thr412Asnfs*5) Frameshift insertion <0.01% (COSMIC v99) Predicted loss of function due to premature stop
Mutation functional classification

Loss of Function (LOF)

Frameshift insertion (c.1234_1235insA) leads to truncated protein; likely loss of function.

Gain of Function (GOF)

No gain-of-function mutations reported in GPA33.

Dominant Negative (DN)

No dominant-negative mutations described for GPA33.

Gene Ontology (GO)

• plasma membrane (GO:0005886) • cell adhesion (GO:0007155)
• integral component of membrane (GO:0016021) • anchored component of membrane (GO:0031225)
• auditory receptor cell stereocilium organization (GO:0060088)

Pathways

• Cell adhesion molecules (CAMs) – KEGG hsa04514
• Immunoglobulin superfamily member signaling

Protein Summary

GPA33 is a 319-amino-acid type I transmembrane glycoprotein with an extracellular immunoglobulin-like domain, a single transmembrane helix, and a short cytoplasmic tail. It is heavily glycosylated and forms homodimers on the cell surface. The protein is involved in cell–cell adhesion in the intestinal epithelium and is internalized upon antibody binding, making it a target for radioimmunotherapy and antibody-drug conjugates in colorectal cancer.

Related Products

Product name Cat.No. Species Gene ID
GPA33 Knockout HEK293 Cell Line EDJ-KQ6960 Human 10223 Details Get a Quote
GPA33 Knockout HeLa Cell Line EDJ-KQ55350 Human 10223 Details Get a Quote
GPA33 Knockout A-549 Cell Line EDJ-KQ63831 Human 10223 Details Get a Quote
GPA33 Knockout HCT 116 Cell Line EDJ-KQ72292 Human 10223 Details Get a Quote
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