RHAG (Rh-Associated Glycoprotein)
Key component of the Rh blood group system and ammonium transporter
Gene Information Card
| Symbol | RHAG |
|---|---|
| Full Name | Rh-associated glycoprotein |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.3 |
| NCBI Gene ID | 6005 ncbi.nlm.nih.gov/gene/6005 |
| Ensembl ID | ENSG00000112077 |
| UniProt ID | Q02094 |
| OMIM ID | 180297 |
| HGNC ID | 10006 |
| Aliases | Rh50, RH50A, CD241 |
Description
The RHAG gene encodes the Rh-associated glycoprotein, a critical component of the Rh blood group system. This protein forms a complex with RhD and RhCE polypeptides on red blood cell membranes and functions as an ammonium transporter. RHAG is essential for proper assembly and expression of Rh antigens and plays a role in ammonium transport and carbon dioxide export in erythrocytes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Overhydrated hereditary stomatocytosis (OHST) | Mutations in RHAG disrupt the Rh complex, leading to increased cation permeability and red cell swelling. | OMIM #185000; ClinVar |
| Rh-null syndrome (regulator type) | Loss-of-function mutations in RHAG prevent Rh antigen expression, causing hemolytic anemia with stomatocytosis. | OMIM #268150; ClinVar |
| Hemolytic anemia | Defective RHAG leads to abnormal red cell morphology and reduced survival. | NCBI Gene; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 28.6 | High |
| Whole blood | 25.3 | High |
| Spleen | 12.1 | Medium |
| Lung | 3.2 | Low |
| Kidney | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Erythroleukemia cell line (K562) | 15.4 | High expression |
| Lymphoblastoid cell line (GM12878) | 2.1 | Low expression |
| Hepatocellular carcinoma (HepG2) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.316C>T (p.Arg106Trp) | Missense | <0.01% | Associated with overhydrated stomatocytosis; disrupts ammonium transport. |
| c.686G>A (p.Gly229Asp) | Missense | <0.01% | Causes Rh-null phenotype; loss of Rh antigen expression. |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of protein function; regulator type Rh-null. |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Met1Val and p.Gly229Asp abolish RHAG function, leading to Rh-null syndrome and hemolytic anemia.
Gain of Function (GOF)
No gain-of-function mutations reported for RHAG.
Dominant Negative (DN)
p.Arg106Trp acts in a dominant-negative manner, disrupting the Rh complex and causing overhydrated stomatocytosis.
View complete mutation data：
Gene Ontology (GO)
| • Ammonium transmembrane transporter activity (GO:0008519) | • Rh blood group antigen activity (GO:0004020) |
| • Integral component of plasma membrane (GO:0005887) | • Carbon dioxide transport (GO:0015701) |
Pathways
• Rh blood group system (Reactome: R-HSA-9033807)
• Ammonium transport (Reactome: R-HSA-210455)
Protein Summary
The Rh-associated glycoprotein (RHAG) is a 50 kDa integral membrane protein with 12 transmembrane domains. It forms a heterotrimeric complex with RhD and RhCE proteins, essential for Rh antigen expression. RHAG functions as an electroneutral ammonium transporter (NH3/H+ cotransporter) and facilitates CO2 export in erythrocytes. Defects in RHAG cause Rh-null syndrome and overhydrated stomatocytosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RHAG Knockout HEK293 Cell Line | EDJ-KQ5664 | Human | 6005 | Details Get a Quote |
| RHAG Knockout HeLa Cell Line | EDJ-KQ54321 | Human | 6005 | Details Get a Quote |
| RHAG Knockout A-549 Cell Line | EDJ-KQ62816 | Human | 6005 | Details Get a Quote |
| RHAG Knockout HCT 116 Cell Line | EDJ-KQ71280 | Human | 6005 | Details Get a Quote |
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