RHD

Protein identityUniProt · HPA

UniProt accession

Q02161

Gene

RHD

Ensembl

ENSG00000187010

Chromosome

1

Canonical length

417 aa

Protein class

Blood group antigen proteins, CD markers, Disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Plasma membrane

OverviewNCBI Gene

The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene, which encodes the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

417 residues, UniProt reviewed canonical sequence.

>Q02161|RHD
     1  MSSKYPRSVR RCLPLWALTL EAALILLFYF FTHYDASLED QKGLVASYQV GQDLTVMAAI
    61  GLGFLTSSFR RHSWSSVAFN LFMLALGVQW AILLDGFLSQ FPSGKVVITL FSIRLATMSA
   121  LSVLISVDAV LGKVNLAQLV VMVLVEVTAL GNLRMVISNI FNTDYHMNMM HIYVFAAYFG
   181  LSVAWCLPKP LPEGTEDKDQ TATIPSLSAM LGALFLWMFW PSFNSALLRS PIERKNAVFN
   241  TYYAVAVSVV TAISGSSLAH PQGKISKTYV HSAVLAGGVA VGTSCHLIPS PWLAMVLGLV
   301  AGLISVGGAK YLPGCCNRVL GIPHSSIMGY NFSLLGLLGE IIYIVLLVLD TVGAGNGMIG
   361  FQVLLSIGEL SLAIVIALMS GLLTGLLLNL KIWKAPHEAK YFDDQVFWKF PHLAVGF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RHD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

11

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RHD.

Disease | AllUniProt

Conditions RHD is implicated in, by any mechanism.

• Hemolytic disease of fetus and newborn, RH-induced (HDFNRH) MIM:619462

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 78 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• RHD DEL
• RhD negative

ReferencesPubMed · IEDB

Publications for RHD from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.95

gnomAD pLI

0

gnomAD missense Z

-0.33

DepMap mean gene effect

0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ammonium homeostasis
• ammonium transmembrane transport

Molecular functions

• ammonium channel activity

Cellular components

• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Blood group Rhesus C/E/D polypeptide
• Ammonium transporter AmtB-like domain
• Ammonium/urea transporter
• Ammonium Transporter Family

KeywordsUniProt

• Blood group antigen
• Cell membrane
• Lipoprotein
• Membrane
• Palmitate
• Transmembrane
• Transmembrane helix