RHD (gene) explained

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.

Further reading

• Polin H, Danzer M, Gaszner W, Broda D, St-Louis M, Pröll J, Hofer K, Gabriel C . Identification of RHD alleles with the potential of anti-D immunization among seemingly D- blood donors in Upper Austria . Transfusion . 49 . 4 . 676–81 . Apr 2009 . 19170995 . 10.1111/j.1537-2995.2008.02046.x . 205717360 .
• Silvy M, Simon S, Gouvitsos J, Di Cristofaro J, Ferrera V, Chiaroni J, Bailly P . Weak D and DEL alleles detected by routine SNaPshot genotyping: identification of four novel RHD alleles . Transfusion . 51 . 2 . 401–11 . Feb 2011 . 20723165 . 10.1111/j.1537-2995.2010.02830.x . 7760367 . free .
• Flegel WA, von Zabern I, Doescher A, Wagner FF, Vytisková J, Písacka M . DCS-1, DCS-2, and DFV share amino acid substitutions at the extracellular RhD protein vestibule . Transfusion . 48 . 1 . 25–33 . Jan 2008 . 17900276 . 10.1111/j.1537-2995.2007.01506.x . 30661322 . free .
• Zhuo CS, Zhuo XF, Guo YJ, Wang CQ . [RHD gene polymorphism of RhD negative individuals in population of Fujian province] . Zhongguo Shi Yan Xue Ye Xue Za Zhi . 16 . 2 . 435–8 . Apr 2008 . 18426681 .
• Wagner FF, Flegel WA . Review: the molecular basis of the Rh blood group phenotypes . Immunohematology / American Red Cross . 20 . 1 . 23–36 . 2020 . 10.21307/immunohematology-2019-419 . 15373666 . 9980290 . free .
• Callebaut I, Dulin F, Bertrand O, Ripoche P, Mouro I, Colin Y, Mornon JP, Cartron JP . Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures . Transfusion Clinique et Biologique . 13 . 1–2 . 70–84 . 2006 . 16584906 . 10.1016/j.tracli.2006.02.001 .
• Cartron JP . Defining the Rh blood group antigens. Biochemistry and molecular genetics . Blood Reviews . 8 . 4 . 199–212 . Dec 1994 . 7888828 . 10.1016/0268-960x(94)90108-2 .
• Martínez H, Rodríguez-Larralde A, Izaguirre MH, De Guerra DC . Admixture estimates for Caracas, Venezuela, based on autosomal, Y-chromosome, and mtDNA markers . Human Biology . 79 . 2 . 201–13 . Apr 2007 . 18027815 . 10.1353/hub.2007.0032 . 21169396 .
• Ye L, Yue D, Wo D, Ding X, Guo S, Li Q, Guo Z, Zhu Z . Molecular bases of unexpressed RHD alleles in Chinese D- persons . Transfusion . 49 . 8 . 1655–60 . Aug 2009 . 19392776 . 10.1111/j.1537-2995.2009.02181.x . 21246262 .
• Pirelli KJ, Pietz BC, Johnson ST, Pinder HL, Bellissimo DB . 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 . Dec 2010 . 21072752 . 10.1002/pd.2652 . 12935058 .
• Flegr J, Novotná M, Fialová A, Kolbeková P, Gasová Z . The influence of RhD phenotype on toxoplasmosis- and age-associated changes in personality profile of blood donors . Folia Parasitologica . 57 . 2 . 143–50 . Jun 2010 . 20608477 . 10.14411/fp.2010.018 . free .
• Wang XD, Wang BL, Ye SL, Liao YQ, Wang LF, He ZM . 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 . Jul 2009 . 19545247 . 10.1111/j.1365-2362.2009.02148.x . 24127883 .
• Li Z, Shao CP . Sequencing analysis of RHD intron 7 and 9 . Transfusion and Apheresis Science . 40 . 3 . 169–73 . Jun 2009 . 19364677 . 10.1016/j.transci.2009.03.004 .
• Feller JM, Simpson AM, Nelson M, Swan MA, O'Connell PJ, Hawthorne WJ, Tao C, O'Brien BA . Growth-promoting effect of Rh(D) antibody on human pancreatic islet cells . The Journal of Clinical Endocrinology and Metabolism . 93 . 9 . 3560–7 . Sep 2008 . 18544617 . 10.1210/jc.2008-0510 . free . 10453/9441 . free .
• Schmid P, von Zabern I, Scharberg EA, Wagner FF, Flegel WA . 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 . Jan 2010 . 20233350 . 3482507 . 10.1111/j.1537-2995.2009.02446.x .
• Liu HC, Eng HL, Yang YF, Wang YH, Lin KT, Wu HL, Lin TM . Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: a mechanism study . Biochimica et Biophysica Acta (BBA) - General Subjects . 1800 . 6 . 565–73 . Jun 2010 . 20188798 . 10.1016/j.bbagen.2010.02.006 .
• Mineeva NV, Elkhina EV, Bodrova NN, Zavarzina OA, Priezzheva LS, Poedinenko IV . [D antigen varieties and determination of Rhesus factor] . Klinicheskaia Laboratornaia Diagnostika . 3 . 17–9 . Mar 2009 . 19388479 .
• Yuan S, Davis R, Lu Q, Goldfinger D, Ziman AF . Low risk of alloimmunization to the D antigen in D- orthotopic liver transplant recipients receiving D+ RBCs perioperatively . Transfusion . 48 . 12 . 2653–5 . Dec 2008 . 19055536 . 10.1111/j.1537-2995.2008.01959.x . 10625455 .
• Avent ND, Reid ME . The Rh blood group system: a review . Blood . 95 . 2 . 375–87 . Jan 2000 . 10627438 . 10.1182/blood.V95.2.375. 13803474 .
• Denomme GA, Wang D, Matheson KA, Titolo D . 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 . Jul 2009 . 19374729 . 10.1111/j.1537-2995.2009.02162.x . 31785967 . free .

See also

• ABO (gene)

Notes and References

1. Web site: Entrez Gene: Rh blood group.
2. Westhoff CM . The structure and function of the Rh antigen complex . Seminars in Hematology . 44 . 1 . 42–50 . Jan 2007 . 17198846 . 1831834 . 10.1053/j.seminhematol.2006.09.010 .
3. Gruswitz F, Chaudhary S, Ho JD, Schlessinger A, Pezeshki B, Ho CM, Sali A, Westhoff CM, Stroud RM . 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 . May 2010 . 20457942 . 2906887 . 10.1073/pnas.1003587107 . 2010PNAS..107.9638G . free .