CD33
CD33 Molecule (Siglec-3) – Myeloid Cell Surface Antigen and Immunotherapy Target
Gene Information Card
| Symbol | CD33 |
|---|---|
| Full Name | CD33 Molecule |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 945 ncbi.nlm.nih.gov/gene/945 |
| Ensembl ID | ENSG00000105383 |
| UniProt ID | P20138 |
| OMIM ID | 159590 |
| HGNC ID | 1659 |
| Aliases | Siglec-3, gp67, SIGLEC3 |
Description
CD33 (Siglec-3) is a transmembrane receptor expressed on myeloid cells, including monocytes, macrophages, and granulocytes. It belongs to the sialic acid-binding immunoglobulin-like lectin (Siglec) family and mediates cell-cell interactions, immune regulation, and endocytosis. CD33 is a well-established target for antibody-based therapies in acute myeloid leukemia (AML) due to its high expression on leukemic blasts.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | CD33 is overexpressed on AML blasts; targeted by gemtuzumab ozogamicin (anti-CD33 antibody-drug conjugate) | ClinVar, COSMIC |
| Myelodysplastic Syndromes (MDS) | CD33 expression on dysplastic myeloid cells; potential therapeutic target | ClinVar |
| Alzheimer's Disease | CD33 risk variant (rs3865444) associated with increased amyloid-beta accumulation and microglial dysfunction | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 28.5 | High |
| Whole Blood | 18.2 | High |
| Spleen | 12.1 | Medium |
| Lung | 6.3 | Medium |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (promyelocytic leukemia) | 35.2 | High expression; used in AML research |
| THP-1 (monocytic leukemia) | 42.8 | Very high expression; model for monocyte/macrophage studies |
| K-562 (chronic myeloid leukemia) | 1.5 | Low expression |
| HEK293 (embryonic kidney) | 0.3 | No significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3865444 (promoter SNP) | SNP | ~30% (global) | Associated with reduced CD33 expression and altered microglial function in Alzheimer's disease |
| c.14C>T (p.Ala5Val) | Missense | <0.1% | Rare variant; functional impact unknown |
| CD33-ITD (internal tandem duplication) | Structural variant | <1% | Reported in AML; may alter receptor signaling |
Mutation functional classification
Loss of Function (LOF)
rs3865444 reduces CD33 expression, leading to impaired sialic acid binding and altered immune regulation.
Gain of Function (GOF)
Not well characterized; no common gain-of-function mutations reported.
Dominant Negative (DN)
No evidence for dominant-negative effects in CD33.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Immune System (Reactome: R-HSA-168256)
• Siglec Signaling (Reactome: R-HSA-6798695)
• Myeloid Cell Differentiation (KEGG: hsa04640)
Protein Summary
CD33 (Siglec-3) is a 67 kDa transmembrane glycoprotein with an extracellular V-set Ig-like domain that binds sialic acid residues, and a cytoplasmic tail containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). It functions as an inhibitory receptor on myeloid cells, modulating cytokine production, phagocytosis, and cell survival. CD33 is a key biomarker and therapeutic target in acute myeloid leukemia, and its genetic variants influence susceptibility to Alzheimer's disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD33 Knockout HEK293 Cell Line | EDJ-KQ17685 | Human | 945 | Details Get a Quote |
| CD33 Knockout HCT 116 Cell Line | EDJ-KQ18435 | Human | 945 | Details Get a Quote |
| CD33 Knockout HeLa Cell Line | EDJ-KQ52833 | Human | 945 | Details Get a Quote |
| CD33 Knockout A-549 Cell Line | EDJ-KQ61303 | Human | 945 | Details Get a Quote |
