ART4 Gene (ADP-Ribosyltransferase 4)
Gene encoding a glycosylphosphatidylinositol (GPI)-anchored ADP-ribosyltransferase involved in immune regulation and blood group antigen expression.
Gene Information Card
| Symbol | ART4 |
|---|---|
| Full Name | ADP-ribosyltransferase 4 (inactive) (Dombrock blood group) |
| Gene Type | protein-coding |
| Chromosomal Location | 12p12.3 |
| NCBI Gene ID | 420 ncbi.nlm.nih.gov/gene/420 |
| Ensembl ID | ENSG00000111339 |
| UniProt ID | Q93070 |
| OMIM ID | 110600 |
| HGNC ID | 727 |
| Aliases | CD297, DO, Dombrock blood group antigen |
Description
ART4 (ADP-ribosyltransferase 4) encodes a glycosylphosphatidylinositol (GPI)-anchored protein that belongs to the ADP-ribosyltransferase family. Although the encoded protein is catalytically inactive due to mutations in the active site, it functions as a cell surface receptor and carries the Dombrock blood group antigens (Doa, Dob, Gya, Hy, Joa). ART4 is expressed on erythrocytes and various immune cells, and its polymorphisms are clinically relevant in transfusion medicine and autoimmune disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dombrock blood group incompatibility | Polymorphisms in ART4 define Dombrock antigens; alloimmunization can occur upon transfusion of incompatible blood. | OMIM #110600 |
| Hemolytic transfusion reaction | Anti-Dombrock antibodies (anti-Doa, anti-Dob) can cause delayed hemolytic transfusion reactions. | ClinVar, NCBI |
| Autoimmune hemolytic anemia | Autoantibodies targeting ART4 may contribute to red blood cell destruction. | OMIM, literature |
| Cancer (potential role) | ART4 expression is altered in certain cancers; GPI-anchored proteins may modulate tumor immune evasion. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | 12.3 | Medium |
| Spleen | 8.7 | Medium |
| Bone marrow | 6.5 | Low |
| Lung | 3.2 | Low |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| HL-60 (promyeloblast) | 11.8 | Medium expression |
| HEK 293 (embryonic kidney) | 2.1 | Low expression |
| HeLa (cervical carcinoma) | 1.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.793A>G (p.Asn265Asp) | missense | 0.5% (global) | Defines Doa/Dob blood group antigen; alters GPI anchor attachment efficiency. |
| c.350C>T (p.Thr117Met) | missense | 0.1% | Associated with Hy- phenotype; loss of Hy antigen. |
| c.442C>T (p.Arg148Trp) | missense | 0.05% | Associated with Jo(a-) phenotype; loss of Joa antigen. |
| c.624C>G (p.Ile208Met) | missense | 0.2% | Defines Gya antigen; rare in most populations. |
Mutation functional classification
Loss of Function (LOF)
Mutations such as c.350C>T (Thr117Met) and c.442C>T (Arg148Trp) disrupt GPI anchor attachment or protein folding, leading to loss of specific Dombrock antigens on the cell surface.
Gain of Function (GOF)
No known gain-of-function mutations reported for ART4.
Dominant Negative (DN)
No dominant-negative effects documented; ART4 functions as a monomeric GPI-anchored protein.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ADP-ribosylation (Reactome: R-HSA-196854)
• Blood group antigen biosynthesis (Reactome: R-HSA-9033808)
• GPI-anchor biosynthesis (Reactome: R-HSA-163125)
Protein Summary
The ART4 protein (UniProt Q93070) is a 314-amino-acid, GPI-anchored cell surface glycoprotein. It is catalytically inactive as an ADP-ribosyltransferase due to substitutions in the NAD+-binding site. The protein carries the Dombrock blood group antigens and is expressed primarily on erythrocytes and hematopoietic cells. Structural polymorphisms define the Doa/Dob, Gya, Hy, and Joa antigens, which are clinically important in transfusion medicine. ART4 may also play a role in immune modulation through its GPI anchor and cell surface localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ART4 Knockout HEK293 Cell Line | EDJ-KQ3428 | Human | 420 | Details Get a Quote |
| ART4 Knockout HeLa Cell Line | EDJ-KQ52668 | Human | 420 | Details Get a Quote |
| ART4 Knockout A-549 Cell Line | EDJ-KQ61139 | Human | 420 | Details Get a Quote |
| ART4 Knockout HCT 116 Cell Line | EDJ-KQ69628 | Human | 420 | Details Get a Quote |
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