Details for: RHBG

Gene ID: 57127

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RHBG

Ensembl ID: ENSG00000132677

Description: Rh family B glycoprotein

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • renal alpha-intercalated cell CL0005011
    CSI 3.6
    rCSI 4.81%
    PRS 98.94
  • renal beta-intercalated cell CL0002201
    CSI 2.41
    rCSI 5.75%
    PRS 98.38
  • renal principal cell CL0005009
    CSI 2.07
    rCSI 5.39%
    PRS 98.49
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.58
    rCSI 4%
    PRS 97.52
  • kidney collecting duct intercalated cell CL1001432
    CSI 1.14
    rCSI 8.15%
    PRS 96.91
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.37
    rCSI 3.9%
    PRS 97.07

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RHBG](/details-gene/57127) (Rhesus blood group family type B glycoprotein) is a protein-coding gene located on chromosome 1q22. It functions as a transmembrane transporter, primarily facilitating the movement of ammonium and, to a lesser extent, carbon dioxide across the plasma membrane ([Link](https://doi.org/10.1074/jbc.m007528200), [Link](https://doi.org/10.1007/s00232-013-9593-0)). **Overall**, expression data reveals that [RHBG](/details-gene/57127) is a highly specific marker for specialized epithelial cells within the kidney's collecting duct system, including [renal alpha-intercalated cells](/details-cell/CL0005011) and [renal principal cells](/details-cell/CL0005009). Its localization to the basolateral membrane and its transport activity are critical for renal ammonium homeostasis and systemic acid-base balance ([Link](https://doi.org/10.1113/jphysiol.2004.067728)). ## Cellular Roles and Expression Landscape The expression profile of [RHBG](/details-gene/57127) demonstrates a highly restricted and significant role within the renal system. **Overall**, the gene shows its highest significance in cell types of the distal nephron and collecting ducts, which are responsible for the final regulation of urine composition and systemic pH. The most significant expression is observed in: - [renal alpha-intercalated cell](/details-cell/CL0005011) (CSI: 3.60) - [renal beta-intercalated cell](/details-cell/CL0002201) (CSI: 2.41) - [renal principal cell](/details-cell/CL0005009) (CSI: 2.07) - [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 1.58) This specific expression pattern strongly suggests that [RHBG](/details-gene/57127) is a key component of the machinery governing transepithelial transport in the kidney. In these polarized epithelial cells, [RHBG](/details-gene/57127) is localized to the [basolateral plasma membrane](/details-cell/GO:0016323), a process dependent on a tyrosine-based signal and interaction with ankyrin-G ([Link](https://doi.org/10.1074/jbc.m413351200)). This strategic positioning allows it to transport ammonium from the cell into the interstitium, completing the process of renal ammonia excretion which is vital for net acid elimination. Its high significance in both alpha (acid-secreting) and beta (base-secreting) intercalated cells highlights its fundamental role in the bidirectional regulation of acid-base homeostasis. ## Pathways and Molecular Function Functionally, [RHBG](/details-gene/57127) is annotated as a transporter involved in maintaining physiological balance. Its primary role is defined by the Reactome pathway [Rhesus glycoproteins mediate ammonium transport](/details-pathway/R-HSA-444411) and the Gene Ontology process [ammonium transmembrane transport](/details-cell/GO:0072488). The gene product exhibits [ammonium channel activity](/details-cell/GO:0008519), enabling the electroneutral transport of NH4+/NH3 across the cell membrane ([Link](https://doi.org/10.1113/jphysiol.2004.067728), [Link](https://doi.org/10.1042/bj20050657)). In addition to ammonium, [RHBG](/details-gene/57127) is also implicated in [carbon dioxide transmembrane transport](/details-cell/GO:0035378), though its permeability to CO2 is lower than to NH3 ([Link](https://doi.org/10.1007/s00232-013-9593-0)). This dual function suggests a coordinated role in managing both nitrogenous waste and acid-base equivalents. The protein's function is structurally supported by its interaction with the cytoskeleton, specifically through [ankyrin binding](/details-cell/GO:0030506), which anchors it to the [spectrin-associated cytoskeleton](/details-cell/GO:0014731) at the basolateral membrane. This interaction is critical for its stable expression and proper localization, ensuring efficient vectorial transport in polarized kidney cells. ## Research Directions The highly specific expression and critical homeostatic function of [RHBG](/details-gene/57127) suggest its dysregulation could be central to specific renal pathologies. **Proposed Hypotheses:** 1. Given its essential role in the final step of ammonia excretion in intercalated cells, it is hypothesized that loss-of-function mutations or epigenetic silencing of [RHBG](/details-gene/57127) are an underlying cause of certain idiopathic forms of distal renal tubular acidosis (dRTA), characterized by impaired urinary acidification and metabolic acidosis. 2. It is hypothesized that the transport activity of [RHBG](/details-gene/57127) is post-translationally regulated by physiological signals of acidosis or alkalosis, such as local pH changes or phosphorylation events, allowing for dynamic adaptation of renal ammonia excretion in response to systemic acid-base demands. **Experimental Approach:** To test the second hypothesis regarding post-translational regulation, a robust experimental plan could be implemented. A kidney epithelial cell line (e.g., MDCK or mpkCCD) could be engineered to stably express a C-terminally tagged version of human [RHBG](/details-gene/57127). These cells would be cultured on permeable supports to establish a polarized monolayer. The cells would then be subjected to either acidic (e.g., pH 6.9) or alkaline (e.g., pH 7.8) medium for several hours. A combination of immunoprecipitation followed by mass spectrometry (IP-MS) could be used to identify changes in the [RHBG](/details-gene/57127) phosphorylation profile or interacting proteins under different pH conditions. Parallel functional assays using 15N-labeled ammonium would directly measure whether these pH-induced changes correlate with altered basolateral transport activity. **Therapeutic Potential:** [RHBG](/details-gene/57127) is unlikely to be a conventional therapeutic target for inhibition or activation, as its function is homeostatic. Its primary clinical relevance lies in its potential as a diagnostic marker and its role in the pathophysiology of renal transport disorders. Understanding its regulatory mechanisms could, however, open new therapeutic avenues. For instance, developing small molecules that enhance [RHBG](/details-gene/57127) transport activity could potentially be beneficial in conditions of impaired renal ammonia excretion, such as chronic kidney disease or certain stages of hepatic encephalopathy where systemic ammonia levels are elevated. Conversely, targeted inhibition is not a likely strategy due to the risk of inducing severe metabolic acidosis.

Genular Protein ID: 2299931081

Symbol: RHBG_HUMAN

Name: Rhesus blood group family type B glycoprotein

UniProtKB Accession Codes:

Q9H310 A8K475 Q5SZW4 Q5SZW6 Q5SZW7 Q6P193 Q6YJI2 Q6YJI3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEBI 3 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 1 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 1 RefSeq 3 Rhea 7 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11024028

Title: Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals.

PubMed ID: 11024028

DOI: 10.1074/jbc.m007528200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15284342

Title: Electroneutral ammonium transport by basolateral rhesus B glycoprotein.

PubMed ID: 15284342

DOI: 10.1113/jphysiol.2004.067728

PubMed ID: 15929723

Title: Human Rhesus B and Rhesus C glycoproteins: properties of facilitated ammonium transport in recombinant kidney cells.

PubMed ID: 15929723

DOI: 10.1042/bj20050657

PubMed ID: 15611082

Title: The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells.

PubMed ID: 15611082

DOI: 10.1074/jbc.m413351200

PubMed ID: 24077989

Title: Relative CO(2)/NH(3) permeabilities of human RhAG, RhBG and RhCG.

PubMed ID: 24077989

DOI: 10.1007/s00232-013-9593-0

Sequence Information:

  • Length: 458
  • Mass: 49481
  • Checksum: 8266F94B637DEF93
  • Sequence:
    • MAGSPSRAAG RRLQLPLLCL FLQGATAVLF AVFVRYNHKT DAALWHRSNH SNADNEFYFR 
YPSFQDVHAM VFVGFGFLMV FLQRYGFSSV GFTFLLAAFA LQWSTLVQGF LHSFHGGHIH 
VGVESMINAD FCAGAVLISF GAVLGKTGPT QLLLMALLEV VLFGINEFVL LHLLGVRDAG 
GSMTIHTFGA YFGLVLSRVL YRPQLEKSKH RQGSVYHSDL FAMIGTIFLW IFWPSFNAAL 
TALGAGQHRT ALNTYYSLAA STLGTFALSA LVGEDGRLDM VHIQNAALAG GVVVGTSSEM 
MLTPFGALAA GFLAGTVSTL GYKFFTPILE SKFKVQDTCG VHNLHGMPGV LGALLGVLVA 
GLATHEAYGD GLESVFPLIA EGQRSATSQA MHQLFGLFVT LMFASVGGGL GGLLLKLPFL 
DSPPDSQHYE DQVHWQVPGE HEDKAQRPLR VEEADTQA