RHD (gene)

Rh blood group, D antigen
Identifiers
Symbols	RHD ; CD240D; DIIIc; RH; RH30; RHCED; RHDVA(TT); RHDel; RHPII; RHXIII; Rh4; RhDCw; RhII; RhK562-II; RhPI
External IDs	OMIM: 111680 MGI: 1202882 HomoloGene: 7918 GeneCards: RHD Gene
Gene ontology Molecular function • ammonium transmembrane transporter activity Cellular component • integral component of plasma membrane Biological process • ammonium transmembrane transport Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6007	19746
Ensembl	ENSG00000187010	ENSMUSG00000028825
UniProt	Q02161	Q8CF94
RefSeq (mRNA)	NM_001127691	NM_011270
RefSeq (protein)	NP_001121163	NP_035400
Location (UCSC)	Chr 1: 25.27 – 25.33 Mb	Chr 4: 134.86 – 134.9 Mb
PubMed search

Rh blood group, D antigen also known as Rh polypeptide 1 (RhPI) or cluster of differentiation 240D (CD240D) is a protein that in humans is encoded by the RHD gene.^[1]

The RHD gene codes for the RhD erythrocyte membrane protein that is the Rh factor antigen of the Rh blood group system.^[2] RHD has sequence similarity to RHCE, RhAG, RhBG, and RhCG and these five genes constitute the Rh family. It was proposed that the erythrocyte Rh complex is a heterotrimer of RhAG, RhD, and RhCE protein subunits.^[3] RhAG is a functional ammonia transporter and is required for normal cell surface expression of RhD and RhCE. Patients who lack RhD/RhCE/RhAG on the surface of their erythrocytes have hemolytic anemia . Antibodies to the RhD protein can cause Rh disease.

Model organisms

Rhd knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Abnormal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of RHD function. A conditional knockout mouse line, called Rhd^{tm1a(EUCOMM)Wtsi[8][9]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty five tests were carried out on mutant mice and one significant abnormality was observed: homozygous mutant males had a decrease in mean corpuscular haemoglobin.^[6]

References

1. "Entrez Gene: Rh blood group".
2. Westhoff CM (Jan 2007). "The structure and function of the Rh antigen complex". Seminars in Hematology 44 (1): 42–50. doi:10.1053/j.seminhematol.2006.09.010. PMC 1831834. PMID 17198846.
3. Gruswitz F, Chaudhary S, Ho JD, Schlessinger A, Pezeshki B, Ho CM, Sali A, Westhoff CM, Stroud RM (May 2010). "Function of human Rh based on structure of RhCG at 2.1 A". Proceedings of the National Academy of Sciences of the United States of America 107 (21): 9638–43. doi:10.1073/pnas.1003587107. PMC 2906887. PMID 20457942.
4. "Salmonella infection data for Rhd". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Rhd". Wellcome Trust Sanger Institute.
6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
13. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Polin H, Danzer M, Gaszner W, Broda D, St-Louis M, Pröll J, Hofer K, Gabriel C (Apr 2009). "Identification of RHD alleles with the potential of anti-D immunization among seemingly D- blood donors in Upper Austria". Transfusion 49 (4): 676–81. doi:10.1111/j.1537-2995.2008.02046.x. PMID 19170995.
• Silvy M, Simon S, Gouvitsos J, Di Cristofaro J, Ferrera V, Chiaroni J, Bailly P (Feb 2011). "Weak D and DEL alleles detected by routine SNaPshot genotyping: identification of four novel RHD alleles". Transfusion 51 (2): 401–11. doi:10.1111/j.1537-2995.2010.02830.x. PMID 20723165.
• Flegel WA, von Zabern I, Doescher A, Wagner FF, Vytisková J, Písacka M (Jan 2008). "DCS-1, DCS-2, and DFV share amino acid substitutions at the extracellular RhD protein vestibule". Transfusion 48 (1): 25–33. doi:10.1111/j.1537-2995.2007.01506.x. PMID 17900276.
• Zhuo CS, Zhuo XF, Guo YJ, Wang CQ (Apr 2008). "[RHD gene polymorphism of RhD negative individuals in population of Fujian province]". Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology 16 (2): 435–8. PMID 18426681.
• Wagner FF, Flegel WA (2004). "Review: the molecular basis of the Rh blood group phenotypes". Immunohematology / American Red Cross 20 (1): 23–36. PMID 15373666.
• Callebaut I, Dulin F, Bertrand O, Ripoche P, Mouro I, Colin Y, Mornon JP, Cartron JP (2006). "Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures". Transfusion Clinique Et Biologique 13 (1-2): 70–84. doi:10.1016/j.tracli.2006.02.001. PMID 16584906.
• Cartron JP (Dec 1994). "Defining the Rh blood group antigens. Biochemistry and molecular genetics". Blood Reviews 8 (4): 199–212. doi:10.1016/0268-960x(94)90108-2. PMID 7888828.
• Martínez H, Rodríguez-Larralde A, Izaguirre MH, De Guerra DC (Apr 2007). "Admixture estimates for Caracas, Venezuela, based on autosomal, Y-chromosome, and mtDNA markers". Human Biology 79 (2): 201–13. doi:10.1353/hub.2007.0032. PMID 18027815.
• Ye L, Yue D, Wo D, Ding X, Guo S, Li Q, Guo Z, Zhu Z (Aug 2009). "Molecular bases of unexpressed RHD alleles in Chinese D- persons". Transfusion 49 (8): 1655–60. doi:10.1111/j.1537-2995.2009.02181.x. PMID 19392776.
• Pirelli KJ, Pietz BC, Johnson ST, Pinder HL, Bellissimo DB (Dec 2010). "Molecular determination of RHD zygosity: predicting risk of hemolytic disease of the fetus and newborn related to anti-D". Prenatal Diagnosis 30 (12-13): 1207–12. doi:10.1002/pd.2652. PMID 21072752.
• Flegr J, Novotná M, Fialová A, Kolbeková P, Gasová Z (Jun 2010). "The influence of RhD phenotype on toxoplasmosis- and age-associated changes in personality profile of blood donors". Folia Parasitologica 57 (2): 143–50. doi:10.14411/fp.2010.018. PMID 20608477.
• Wang XD, Wang BL, Ye SL, Liao YQ, Wang LF, He ZM (Jul 2009). "Non-invasive foetal RHD genotyping via real-time PCR of foetal DNA from Chinese RhD-negative maternal plasma". European Journal of Clinical Investigation 39 (7): 607–17. doi:10.1111/j.1365-2362.2009.02148.x. PMID 19545247.
• Li Z, Shao CP (Jun 2009). "Sequencing analysis of RHD intron 7 and 9". Transfusion and Apheresis Science 40 (3): 169–73. doi:10.1016/j.transci.2009.03.004. PMID 19364677.
• Feller JM, Simpson AM, Nelson M, Swan MA, O'Connell PJ, Hawthorne WJ, Tao C, O'Brien BA (Sep 2008). "Growth-promoting effect of Rh(D) antibody on human pancreatic islet cells". The Journal of Clinical Endocrinology and Metabolism 93 (9): 3560–7. doi:10.1210/jc.2008-0510. PMID 18544617.
• Schmid P, von Zabern I, Scharberg EA, Wagner FF, Flegel WA (Jan 2010). "Specific amino acid substitutions cause distinct expression of JAL (RH48) and JAHK (RH53) antigens in RhCE and not in RhD". Transfusion 50 (1): 267–9. doi:10.1111/j.1537-2995.2009.02446.x. PMC 3482507. PMID 20233350.
• Liu HC, Eng HL, Yang YF, Wang YH, Lin KT, Wu HL, Lin TM (Jun 2010). "Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: a mechanism study". Biochimica et Biophysica Acta 1800 (6): 565–73. doi:10.1016/j.bbagen.2010.02.006. PMID 20188798.
• Mineeva NV, Elkhina EV, Bodrova NN, Zavarzina OA, Priezzheva LS, Poedinenko IV (Mar 2009). "[D antigen varieties and determination of Rhesus factor]". Klinicheskaia Laboratornaia Diagnostika (3): 17–9. PMID 19388479.
• Yuan S, Davis R, Lu Q, Goldfinger D, Ziman AF (Dec 2008). "Low risk of alloimmunization to the D antigen in D- orthotopic liver transplant recipients receiving D+ RBCs perioperatively". Transfusion 48 (12): 2653–5. doi:10.1111/j.1537-2995.2008.01959.x. PMID 19055536.
• Avent ND, Reid ME (Jan 2000). "The Rh blood group system: a review". Blood 95 (2): 375–87. PMID 10627438.
• Denomme GA, Wang D, Matheson KA, Titolo D (Jul 2009). "The proximal cis-regulatory region of the RHD/RHCE promoter is 105 bp and contains a 55-bp core devoid of known binding motifs but necessary for transcription". Transfusion 49 (7): 1361–9. doi:10.1111/j.1537-2995.2009.02162.x. PMID 19374729.