Human Gene RHAG (uc003ozk.4) Description and Page Index
  Description: Homo sapiens Rh-associated glycoprotein (RHAG), mRNA.
RefSeq Summary (NM_000324): The protein encoded by this gene is erythrocyte-specific and is thought to be part of a membrane channel that transports ammonium and carbon dioxide across the blood cell membrane. The encoded protein appears to interact with Rh blood group antigens and Rh30 polypeptides. Defects in this gene are a cause of regulator type Rh-null hemolytic anemia (RHN), or Rh-deficiency syndrome.[provided by RefSeq, Mar 2009]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: X64594.1, BC012605.1 [ECO:0000332] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr6:49,572,890-49,604,587 Size: 31,698 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr6:49,573,526-49,604,525 Size: 31,000 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr6:49,572,890-49,604,587)mRNA (may differ from genome)Protein (409 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Ammonium transporter Rh type A; AltName: Full=Erythrocyte membrane glycoprotein Rh50; AltName: Full=Erythrocyte plasma membrane 50 kDa glycoprotein; Short=Rh50A; AltName: Full=Rhesus blood group family type A glycoprotein; Short=Rh family type A glycoprotein; Short=Rh type A glycoprotein; AltName: Full=Rhesus blood group-associated ammonia channel; AltName: Full=Rhesus blood group-associated glycoprotein; AltName: CD_antigen=CD241;
FUNCTION: Associated with rhesus blood group antigen expression. May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane.
SUBUNIT: Heterotetramer.
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
DISEASE: Defects in RHAG are the cause of regulator type Rh-null hemolytic anemia (RHN) [MIM:268150]; also known as Rh-deficiency syndrome. RHN is a form of chronic hemolytic anemia in which the red blood cells have a stomatocytosis and spherocytosis morphology, an increased osmotic fragility, an altered ion transport system, and abnormal membrane phospholipid organization.
SIMILARITY: Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): RHAG
CDC HuGE Published Literature: RHAG
Positive Disease Associations: Lipoproteins, VLDL
Related Studies:
  1. Lipoproteins, VLDL
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.

-  MalaCards Disease Associations
  MalaCards Gene Search: RHAG
Diseases sorted by gene-association score: overhydrated hereditary stomatocytosis* (1580), anemia, hemolytic, rh-null, regulator type* (1550), rh-mod syndrome* (500), rh-null regulator type related hemolytic anemia* (500), stomatocytosis i* (400), rh deficiency syndrome (27), hemolytic anemia (19), null syndrome (12), pulmonary hemosiderosis (11), intracranial hypotension (8), primary systemic mycosis (4), osteogenesis imperfecta, type iii (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.06 RPKM in Whole Blood
Total median expression: 7.66 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -6.6062-0.106 Picture PostScript Text
3' UTR -137.46636-0.216 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR024041 - NH4_transpt_AmtB-like
IPR002229 - RhesusRHD

Pfam Domains:
PF00909 - Ammonium Transporter Family

SCOP Domains:
111352 - Ammonium ransporter (Pfam 00909)

ModBase Predicted Comparative 3D Structure on Q02094
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologGenome BrowserGenome Browser
Gene Details   Gene DetailsGene Details
Gene Sorter   Gene SorterGene Sorter
  Ensembl WormBaseSGD
  Protein Sequence Protein SequenceProtein Sequence
  Alignment AlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0008519 ammonium transmembrane transporter activity
GO:0022840 leak channel activity
GO:0030506 ankyrin binding
GO:0035379 carbon dioxide transmembrane transporter activity

Biological Process:
GO:0006873 cellular ion homeostasis
GO:0015670 carbon dioxide transport
GO:0015672 monovalent inorganic cation transport
GO:0015695 organic cation transport
GO:0015696 ammonium transport
GO:0015701 bicarbonate transport
GO:0035378 carbon dioxide transmembrane transport
GO:0048821 erythrocyte development
GO:0060586 multicellular organismal iron ion homeostasis
GO:0072488 ammonium transmembrane transport

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane

-  Descriptions from all associated GenBank mRNAs
  LP895561 - Sequence 425 from Patent EP3253886.
X64594 - H.sapiens mRNA for 50 kDa erythrocyte plasma membrane glycoprotein.
BC012605 - Homo sapiens Rh-associated glycoprotein, mRNA (cDNA clone MGC:13605 IMAGE:4063377), complete cds.
JD447434 - Sequence 428458 from Patent EP1572962.
JD206022 - Sequence 187046 from Patent EP1572962.
JD045401 - Sequence 26425 from Patent EP1572962.
AF031549 - Homo sapiens mutant erythrocyte membrane glycoprotein Rh50 (Rh50) mRNA, complete cds.
AF178841 - Homo sapiens Rh-null regulator protein mRNA, complete cds.
AF179682 - Homo sapiens isolate Rh-null(HT) mutant Rh50 glycoprotein mRNA, complete cds.
AF179684 - Homo sapiens isolate Rh-null(WO) mutant Rh50 glycoprotein mRNA, complete cds.
AF179685 - Homo sapiens isolate Rh-null(WO) mutant Rh50 glycoprotein mRNA, alternatively spliced, complete cds.
AF187847 - Homo sapiens truncated Rh50 glycoprotein mRNA, complete cds.
AB938314 - Homo sapiens RHAG mRNA for Rh-associated glycoprotein, complete cds.
AF031548 - Homo sapiens erythrocyte membrane glycoprotein Rh50 (Rh50) mRNA, allele Asn242, complete cds.
KJ543706 - Homo sapiens RHAG (RHAG) mRNA, RHAG*01.13 allele, complete cds.
AK313505 - Homo sapiens cDNA, FLJ94061, highly similar to Homo sapiens Rhesus blood group-associated glycoprotein (RHAG), mRNA.
DQ892782 - Synthetic construct clone IMAGE:100005412; FLH189677.01X; RZPDo839H1074D Rh-associated glycoprotein (RHAG) gene, encodes complete protein.
DQ896030 - Synthetic construct Homo sapiens clone IMAGE:100010490; FLH189673.01L; RZPDo839H1064D Rh-associated glycoprotein (RHAG) gene, encodes complete protein.
AB590393 - Synthetic construct DNA, clone: pFN21AE1418, Homo sapiens RHAG gene for Rh-associated glycoprotein, without stop codon, in Flexi system.
KJ904549 - Synthetic construct Homo sapiens clone ccsbBroadEn_13943 RHAG gene, encodes complete protein.
MH397221 - Homo sapiens mutant Rh associated glycoprotein (RHAG) mRNA, complete cds.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q02094 (Reactome details) participates in the following event(s):

R-HSA-444416 RHAG transports NH4+ from cytosol to extracellular region (red blood cells)
R-HSA-1237069 RhAG passively translocates carbon dioxide from the extracellular region to the cytosol
R-HSA-1247645 RhAG passively translocates carbon dioxide from the cytosol to the extracellular region
R-HSA-444411 Rhesus glycoproteins mediate ammonium transport.
R-HSA-1237044 Erythrocytes take up carbon dioxide and release oxygen
R-HSA-1247673 Erythrocytes take up oxygen and release carbon dioxide
R-HSA-425366 Transport of bile salts and organic acids, metal ions and amine compounds
R-HSA-425428 Amine compound SLC transporters
R-HSA-1480926 O2/CO2 exchange in erythrocytes
R-HSA-425407 SLC-mediated transmembrane transport
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: B2R8T8, NM_000324, NP_000315, O43514, Q02094, Q7L8L3, Q9H454, RH50, RHAG_HUMAN
UCSC ID: uc003ozk.4
RefSeq Accession: NM_000324
Protein: Q02094 (aka RHAG_HUMAN)
CCDS: CCDS4927.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_000324.2
exon count: 10CDS single in 3' UTR: no RNA size: 1953
ORF size: 1230CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2660.00frame shift in genome: no % Coverage: 98.72
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.