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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RHAG
Rh associated glycoprotein
Chromosome 6 Β· 6p12.3
NCBI Gene: 6005Ensembl: ENSG00000112077.18HGNC: HGNC:10006UniProt: Q02094
60PubMed Papers
22Diseases
0Drugs
18Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingammonium channel activitymethylammonium transmembrane transporter activityleak channel activityRh deficiency syndromeoverhydrated hereditary stomatocytosisplacental retentionnon-small cell lung carcinoma
✦AI Summary

RHAG (Rh-associated glycoprotein) is a transmembrane protein essential for erythrocyte membrane stability and function. As a core component of the ankyrin-1 complex, RHAG tethers the spectrin-actin cytoskeleton to the erythrocyte membrane and facilitates clustering of membrane proteins 1. RHAG forms a heterotrimer with RHCE proteins that functions as the primary ammonium transporter in red blood cells, mediating NH4+ and methylammonium transport in both neutral and ionic forms 23. The NH4+ transport is electrogenic and represents the dominant ammonium conductance pathway 3. RHAG may also function as a CO2 channel, though evidence suggests AQP1 plays a more prominent role in CO2 transport 3. Additionally, RHAG regulates RhD membrane expression and is essential for proper Rhesus blood group antigen presentation 4. Clinically, RHAG mutations cause regulator-type Rh-null hemolytic anemia and overhydrated hereditary stomatocytosis, manifesting as morphological and functional erythrocyte abnormalities. Recent findings identify low-prevalence RHAG blood group antigens (RHAG5-7) resulting from rare missense mutations, some implicated in hemolytic disease of the fetus and newborn 5, highlighting RHAG's critical role in transfusion medicine.

Sources cited
1
RHAG is a component of the ankyrin-1 complex that provides stability and shape to the erythrocyte membrane and facilitates membrane protein clustering
PMID: 35835865
2
RhAG functions as an ammonium transporter, capable of promoting both ammonium uptake and efflux
PMID: 11062476
3
RhAG is the major contributor to NH3/ammonium conductance in erythrocytes; CO2 transport may involve AQP1 more prominently than RhAG
PMID: 16574458
4
RhD antigen expression absolutely depends on the presence of RhAG protein, demonstrating RhAG's essential role in Rh antigen expression
PMID: 24260394
5
Rare missense RHAG mutations encoding externally located amino acid changes create low-prevalence blood group antigens implicated in hemolytic disease of the fetus and newborn
PMID: 40146179
Disease Associationsβ“˜22
Rh deficiency syndromeOpen Targets
0.76Strong
overhydrated hereditary stomatocytosisOpen Targets
0.72Strong
placental retentionOpen Targets
0.24Weak
non-small cell lung carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.07Suggestive
carotid artery diseaseOpen Targets
0.06Suggestive
thyroid cancerOpen Targets
0.05Suggestive
lung cancerOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
congenital dyserythropoietic anemia type 4Open Targets
0.04Suggestive
Congenital dyserythropoietic anemia type IVOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
FTH1-related iron overloadOpen Targets
0.04Suggestive
hemochromatosis type 5Open Targets
0.04Suggestive
hemoglobin E diseaseOpen Targets
0.04Suggestive
ulcerative colitisOpen Targets
0.03Suggestive
acute myeloid leukemiaOpen Targets
0.03Suggestive
Overhydrated hereditary stomatocytosisUniProt
Regulator type Rh-null hemolytic anemiaUniProt
Pathogenic Variants18
NM_000324.3(RHAG):c.194T>C (p.Phe65Ser)Pathogenic
Overhydrated hereditary stomatocytosis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 65
NM_000324.3(RHAG):c.157+1G>APathogenic
Rh-null, regulator type|RHAG-related disorder|Overhydrated hereditary stomatocytosis;Rh-null, regulator type|not provided
β˜…β˜…β˜†β˜†2025
NM_000324.3(RHAG):c.1163G>A (p.Trp388Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 388
NM_000324.3(RHAG):c.1034G>A (p.Gly345Asp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 345
NM_000324.3(RHAG):c.212del (p.Phe71fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 71
NM_000324.3(RHAG):c.836G>A (p.Gly279Glu)Likely pathogenic
Rh-null, regulator type|Overhydrated hereditary stomatocytosis
β˜…β˜†β˜†β˜†2024β†’ Residue 279
NM_000324.3(RHAG):c.1067+1G>APathogenic
Rh-null, regulator type|Rh deficiency syndrome
β˜…β˜†β˜†β˜†2023
NM_000324.3(RHAG):c.471C>A (p.Tyr157Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 157
NM_000324.3(RHAG):c.1139-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2017
NM_000324.3(RHAG):c.544G>A (p.Gly182Ser)Pathogenic
Rh-null, regulator type
β˜†β˜†β˜†β˜†2023β†’ Residue 182
NM_000324.3(RHAG):c.920C>T (p.Ser307Phe)Pathogenic
Rh mod blood group phenotype
β˜†β˜†β˜†β˜†2023β†’ Residue 307
NM_000324.3(RHAG):c.447T>G (p.Ile149Met)Pathogenic
Overhydrated hereditary stomatocytosis
β˜†β˜†β˜†β˜†2017β†’ Residue 149
NM_000324.3(RHAG):c.182T>G (p.Ile61Arg)Pathogenic
Overhydrated hereditary stomatocytosis
β˜†β˜†β˜†β˜†2009β†’ Residue 61
NM_000324.3(RHAG):c.1139G>T (p.Gly380Val)Pathogenic
Rh-null, regulator type
β˜†β˜†β˜†β˜†1999β†’ Residue 380
NM_000324.3(RHAG):c.946-1G>APathogenic
Rh-null, regulator type
β˜†β˜†β˜†β˜†1998
NM_000324.3(RHAG):c.236G>A (p.Ser79Asn)Pathogenic
Rh mod blood group phenotype
β˜†β˜†β˜†β˜†1996β†’ Residue 79
NM_000324.3(RHAG):c.154_157delinsGA (p.Pro52fs)Pathogenic
Rh-null, regulator type
β˜†β˜†β˜†β˜†1996β†’ Residue 52
NM_000324.3(RHAG):c.1086del (p.Ala363fs)Pathogenic
Rh-null, regulator type
β˜†β˜†β˜†β˜†1996β†’ Residue 363
View on ClinVar β†—
Related Genes
GATA1Protein interaction100%CD47Protein interaction99%KELProtein interaction99%ANK1Protein interaction93%EPB42Protein interaction93%GYPAProtein interaction93%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
1%
Lung
0%
Liver
0%
Ovary
0%
Brain
0%
Gene Interaction Network
Click a node to explore
RHAGGATA1CD47KELANK1EPB42GYPA
PROTEIN STRUCTURE
Preparing viewer…
PDB7UZQ Β· 2.17 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.73LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.50 [0.35–0.73]
RankingsWhere RHAG stands among ~20K protein-coding genes
  • #7,704of 20,598
    Most Researched60
  • #2,289of 5,498
    Most Pathogenic Variants18
  • #5,660of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedRHAG
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.
PMID: 37247330
Eur Heart J Β· 2023
1.00
2
Architecture of the human erythrocyte ankyrin-1 complex.
PMID: 35835865
Nat Struct Mol Biol Β· 2022
0.90
3
The Rh blood group system: a review.
PMID: 10627438
Blood Β· 2000
0.80
4
An update on the RHAG blood group system.
PMID: 40146179
Immunohematology Β· 2025
0.70
5
Role of RhAG and AQP1 in NH3 and CO2 gas transport in red cell ghosts: a stopped-flow analysis.
PMID: 16574458
Transfus Clin Biol Β· 2006
0.60