RHD*01
(ISBT table: RHD partial D v5.0)
This entry is the RHD reference allele.
standard RHD, standard RHD (RHD*01), wild type D,
Molecular data
Nucleotides:
Amino acids:
Hybrid allele encompassing at least one RHCE exon:
no
Comments on the molecular basis:
- sometimes additional IVS5-38del4 with R1r or R1R1 or R1R2 phenotype
- intronic polymorphism -28G > C was present in 13/13 DCe haplotypes, 13/43 Dce and 1/8 DcE haplotypes; additional intronic IVS2+36A>G mutation in one sample heterozygous for RHef00008 and RHef00442; additional 3'UTR mutation Exon 10 +1377G>A mutation in one sample heterozygous for RHef00008 and RHef00442; additional intronic IVS5+12G>A in one sample heterozygous with RHef00077
- RHD-specific miRNA expression level quantification compared to RHef00122
- description of normal promoter sequence
- intronic sequence established by long range PCR and NGS for R2 haplotype with Genbank accession numbers MG944309 and for R1, R0 and R2 haplotypes with Genbank accession number MG944308
Extracellular position of one or more amino acid substitutions:
Splicing:
Unconventional prediction methods:
Phenotype
Main D phenotype: D positive (last update: Nov. 17, 2019)Reports by D phenotype
- D positive (apparently normal D or undetailed positive D)
- The haplotype in trans has an effect on D antigen expression; dCe haplotype has a suppressive effect
Other RH phenotypes: RH:-2, -3, -4, -5, 12, -19, -23, -31, -54,
Serology with monoclonal anti-D
Antigen Density (Ag/RBC)
- 13283 Ag/RBC, RH:1,2,-3,4,5 sample used as control; derived from the results obtained with 59 of the 59 monoclonal IgG anti-D tested
- 24509 Ag/RBC, RH:1,2,3,4,5 sample used as control; derived from the results obtained with 59 of the 59 monoclonal IgG anti-D tested
- 22778 Ag/RBC, RH:1,2,-3,-4,5 sample used as control; derived from the results obtained with 59 of the 59 monoclonal IgG anti-D tested
- 19710 Ag/RBC, RH:1,-2,3,4,5 sample used as control; derived from the results obtained with 59 of the 59 monoclonal IgG anti-D tested
- 23240 Ag/RBC, RH:1,-2,-3,4,5 sample used as control; derived from the results obtained with 59 of the 59 monoclonal IgG anti-D tested
- Ag/RBC, epitope density profile with 59 monoclonal IgG anti-D (Figure 1)
- range: 17401 - 20807, median 19024 Ag/RBC, range with different monoclonal anti-D from one ccDEe sample used as control
- 20166 Ag/RBC, determined from the results of 55 monoclonal anti-D out of the 55 tested (results above a cutoff); RH:1,-2,-3,4,5 sample used as control
- 10429 Ag/RBC, 1 R1r sample used as control
- 13645 Ag/RBC, RH:1,2,-3,4,5 sample used as control
- range: 6437 - 17634, median: 11668 Ag/RBC, 499 "normal D" R1r samples, 2 monoclonal anti-D
- range: 13617 - 22988, median: 18221 Ag/RBC, 437 "normal D" R2r samples, 2 monoclonal anti-D
- range: 10578 - 28041, median: 19191 Ag/RBC, 480 "normal D" R0r samples, 2 monoclonal anti-D
- 16500 Ag/RBC, DCcEe control, estimated antigen density
- 16884 Ag/RBC, 1 RH:1,2,-3,4,5 sample used as control
- mean: 22105, SD: 2210 Ag/RBC, with 4 monoclonal anti-D; 3 RH:1,-2,-3,4,5 control samples (S2)
- 20726 Ag/RBC, 1 R0r sample used as control, with 12 anti-D (Table S1)
More phenotype data
Rhesus Similarity Index
- 0.74 (RH:1,-2,-3,4,5 sample used as control)
- 0.845 (Rhesus Index expected for standard RhD)
- 0.9 (RH:1,2,-3,4,5 sample used as control)
- 0.84 (RH:1,2,3,4,5 sample used as control) (RH:1,2,-3,-4,5 sample used as control)
- 0.87 (RH:1,-2,3,4,5 sample used as control)
- 0.88 (RH:1,-2,-3,4,5 sample used as control)
- 0.89 (R1r sample)
Haplotype
Main CcEe phenotype association: Ce and cE are the most common associations in Caucasians, ce is the most common association in Afro-Caribbean, but all combinations are possible, see articles (last update: Nov. 9, 2019)ce | Ce | cE | CE | |
---|---|---|---|---|
ce | 111 | 12 | 4 | 0 |
Ce | 0 | 0 | 0 | |
cE | 0 | 0 | ||
CE | 0 |
Reports by CcEe phenotype
- with Ccee 12 samples
- with ce 0 samples (number of samples could not be counted) (Figure 2; presented as a general association, no sample count)
- with Ce 0 samples (Figure 2; presented as a general association, no sample count)
- with cE 0 samples (Figure 2; presented as a general association, no sample count)
- with CE 0 samples (Figure 2; presented as a general association, no sample count)
- with ccEe 4 samples
111 samples
Reports by allele association
- RHCE*01.20.01 (RHCE*733G)
- RHCE*01
- RHCE*ceCF (RHCE*01.20.06)
- RHCE*03
- RHCE*01.20.02 (RHCE*48C,733G)
- RHCE*02
- RHCE*04
- RHCE*01.01 RHCE*ce(48)
- RHCE*Ce(462T)
- RHCE*ce48C, 105T
- RHCE*ce(48C,733G,1006T) (RHCE*ce.20.03)
- RHCE*ceMO
- RHCE*cEMI
- RHCE*ceAR
- RHCE*ceTI
- RHCE*cE(916)
- RHCE*ce733 or RHCE*ce48,733,1006
- RHCE*01 or RHCE*ce48,733,1006
- RHCE*02 or RHCE*ce48,733,1006
- RHCE*ceHAR or RHCE*ce48C
- RHCE*02 or RHCE*ce48C
- RHCE*02 or RHCE*03
- RHCE*02 or RHCE*01
- RHCE*02 or RHCE*ceTI
- RHCE*02 or RHCE*ce733G
- RHCE*ceAG or RHCE*ce733G
- RHCE*ce48C
- RHCE*ceAG
- RHCE*ce48,733,1006
- RHCE*01.01 or RHCE*ce479G, 733G
- RHCE*ceMO or RHCE*03
- RHCE*ceMO or RHCE*CeRN
- RHCE*ce(340,733) or RHCE*03
- RHCE*ceMO or RHCE*ce-D(5)-ce
- RHCE*CeRN or RHCE*ce(733,748)
- RHCE*CeRN or RHCE*ce-(4-9)-ce
- RHCE*CeRN or RHCE*ceMO
- RHCE*cE(733G)
- RHCE*ceVS.01(307T)
- RHCE*ceVS.09
- RHCE*Ce(712G)
- RHCE*Ce−D(9)−Ce
- RHCE*CeVA
- RHCE*cE.14
- RHCE*cE.19
- RHCE*CeCX
- RHCE*Ce−D(2)−Ce
- RHCE*CeN.03
- RHCE*CeN.04
- RHCE*CeN.05
- RHCE*CeN.07
- RHCE*CeN.08
- RHCE*CeRN
- RHCE*cE.18
- RHCE*Ce(1137A) or RHCE*CE
- RHCE*cE or RHCE*ceVS.02
- RHCE*ce or RHCE*cEN.02
- RHCE*ceEK or RHCE*ce
- RHCE*ce or RHCE*ce(48C,712G,733G,787G,800A)
- RHCE*CeN.08 or RHCE*ceAR
- RHCE*ceVS.01 or RHCE*ceVS.09
- RHCE*ce or RHCE*ceJAL
- RHCE*01 or RHCE*01.01
- RHCE*ce or RHCE*ce(285T)
- RHCE*Ce or RHCE*ceLOCR
- RHCE*Ce or RHCE*ceSL.02
- RHCE*Ce or Duplication RHCE*ce
- RHCE*Ce.26 or RHCE*ce
- RHCE*cEEW or RHCE*ce
- RHCE*Ce(436T) or RHCE*ce
- RHCE*Ce(462T) or RHCE*ce
- RHCE*Ce(1153C) or RHCE*ce
- RHCE*Ce−D(2)−Ce or RHCE*ce
- RHCE*CeN.08 or RHCE*ce
- RHCE*CeRN or RHCE*ce
- RHCE*cE or RHCE*ce
- RHCE*cE(92C) or RHCE*Ce
- RHCE*cE(281C,282T) or RHCE*Ce
- RHCE*cE(341A) or RHCE*ce
- RHCE*cE(697G) or RHCE*ce
- RHCE*Ce or RHCE*ceVS.04
- RHCE*cE(361T) or RHCE*ceVS.03
- RHCE*ceVS.01 or RHCE*ceVS.03
- RHCE*ceVS.01 or RHCE*ceTI
- RHCE*ceVS.01 or RHCE*ceBI
- RHCE*ce.01 or RHCE*ce.16
- RHCE*cE or RHCE*cE(602C)
Alloimmunization
Antibodies in carriers
Antibody specificity: D (RH1)
Summary: not considered at risk for allo-anti-D (last update: Nov. 17, 2019)Detailed information
-
Noizat-Pirenne F et al. Transfus Clin Biol (2011)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 8
- Number listed as allo-:
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT: ND
- Autologuous control: ND
- Elution: ND
- Autoadsorption: ND
- Titer: ND
- Was anti-LW excluded?: ND
- Other antibodies detected: ND
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: ND, probable
- Pregnancy history:
- Anti-D Ig history: ND
- Context: among 17 SCD patients with anti-D
- Hemolytic consequences:
- Comment:
-
Dezan MR et al. Blood Cells Mol Dis (2017)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 10 (listed as allo-anti-D or probable allo-anti-D)
- Number listed as auto-: 1
- Number of carriers of the allele assessed:
- DAT: 46.2% of D+ patients with anti-D in this study had positive DAT (which patients are not specified)
- Autologuous control: ND
- Elution: anti-D was eluted in one sample and considered auto-anti-D
- Autoadsorption: ND
- Titer: ND
- Was anti-LW excluded?: ND
- Other antibodies detected: see reference for details
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: yes, number and phenotypes ND
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: SCD patient
- Hemolytic consequences:
- Comment: 3 samples listed with allo-anti-D or probable allo-anti-D, despite apparently standard RHD allele; authors underline that "self-directed anti-D may have been missed"
-
Sippert E et al. Blood Transfus (2015)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 2 (samples heterozygous with RHef00008)
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT: ND
- Autologuous control: ND
- Elution: ND
- Autoadsorption: ND
- Titer: ND
- Was anti-LW excluded?: ND
- Other antibodies detected: ND
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: yes, number and phenotypes ND
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols
- Hemolytic consequences: none of the 13 patients with delayed hemolytic transfusion reactions or decreased survival of transfused RBCs had this allele
- Comment: study does not detail serology for each sample, but mentions performing DAT, autologuous control, eluate studies and adsorption on autologuous RBCs to aid the differenciation of autoantibodies and alloantibodies
-
Westhoff CM et al. Transfusion (2013)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 1 (listed as allo-anti-D, patient heterozygous for RHef00442 and RHef00008)
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT:
- Autologuous control:
- Elution:
- Autoadsorption:
- Titer:
- Was anti-LW excluded?:
- Other antibodies detected:
- Cross matches (with Ab and RBCs from different partial types):
- Transfusion history:
- Pregnancy history:
- Anti-D Ig history:
- Context: among 27 patients referred with different RH alloantibodies, who were found to have RHCE*ceMO allele
- Hemolytic consequences:
- Comment:
-
Chou ST et al. Blood (2013)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 8
- Number listed as allo-:
- Number listed as auto-:
- Number of carriers of the allele assessed: 31
- DAT:
- Autologuous control:
- Elution:
- Autoadsorption:
- Titer:
- Was anti-LW excluded?:
- Other antibodies detected:
- Cross matches (with Ab and RBCs from different partial types):
- Transfusion history:
- Pregnancy history:
- Anti-D Ig history:
- Context: SCD children
- Hemolytic consequences: 3 had delayed hemolytic transfusion reactions
- Comment: anti-D detected in 8 of 31 patients with one conventional and one variant RHD alleles
-
Chou ST et al. Blood (2013)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 13
- Number listed as allo-:
- Number listed as auto-:
- Number of carriers of the allele assessed: 57
- DAT:
- Autologuous control:
- Elution:
- Autoadsorption:
- Titer:
- Was anti-LW excluded?:
- Other antibodies detected:
- Cross matches (with Ab and RBCs from different partial types):
- Transfusion history:
- Pregnancy history:
- Anti-D Ig history:
- Context: SCD children
- Hemolytic consequences: at least 6 had delayed hemolytic transfusion reactions
- Comment: anti-D detected in 13 of 57 patients with conventional RHD only
-
O'Suoji C et al. Pediatr Blood Cancer (2013)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-:
- Number listed as auto-: 1
- Number of carriers of the allele assessed: ND
- DAT: ND
- Autologuous control: ND
- Elution: ND
- Autoadsorption: ND
- Titer: ND
- Was anti-LW excluded?: ND
- Other antibodies detected: anti-RH2, anti-KEL6, anti-Bg, auto-anti-RH5
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: 188 RBC units, chronic transfusion program
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: SCD child
- Hemolytic consequences: unknown
- Comment:
Antibodies in D negative recipients
Alloimmunization in recipients: expected to be possible, see phenotype data
Reports
Summary: reference allele, described in all populations (last update: May 2, 2020)Detailed reports
- 42/58 random donors carrying the allele (regardless of the allele in trans) Malian
- 23/310 (2 heterozygous with RHef00059, 1 with RHef00313; 20 could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056) among 1702 samples tested for the combined presence of RHD c.602G and c.667G (700 Dutch White, 310 South African Black, 319 South African Asians, 197 Curacao Black, 176 Ethiopian Black) South African, Black
- 1/197 (heterozygous with RHef00313) among 1702 samples tested for the combined presence of RHD c.602G and c.667G (700 Dutch White, 310 South African Black, 319 South African Asians, 197 Curacao Black, 176 Ethiopian Black) Curacao (Black)
- 3/319 (2 heterozygous with RHef00059, 1 with RHef00313) among 1702 samples tested for the combined presence of RHD c.602G and c.667G (700 Dutch White, 310 South African Black, 319 South African Asians, 197 Curacao Black, 176 Ethiopian Black) South African (Asian)
- 5/167 (2 heterozygous with RHef00313, 2 with RHef00315; 1 could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056) among 1702 samples tested for the combined presence of RHD c.602G and c.667G (700 Dutch White, 310 South African Black, 319 South African Asians, 197 Curacao Black, 176 Ethiopian Black) Ethiopian (Black)
- 5 or 6/10 (1 heterozygous with RHef00447, 1 sample could be RHef00008 in trans with RHef00317 or RHef00313 with RHef00056) individuals with D positive phenotype Bantu, subgroup Teke, Boma from villages in the north of Léfini river
- 9 or 10/10 (5 heterozygous with RHef00008, 1 sample could be RHef00442 in trans to RHef00020 or RHef00093 in trans to RHef00008) individuals with D positive phenotype Bantu, subgroup Teke, Nziku from villages in the south of Gamboma city
- 5/10 (1 heterozygous with RHef00018) individuals with D positive phenotype Bantu, subgroup Teke, Wumu from villages in the south of Ngabé city
- 7/10 (5 heterozygous with RHef00008, 1 with RHef00313) individuals with D positive phenotype Bantu, subgroup Teke, Kukuya from villages around Djambala city
- 15/60 (7/21 donors, heterozygous with RHef00058; 8/39 patients, heterozygous with RHef00058) among 60 individuals (21 donors, 39 patients) phenotyped as RH:54 and/or submitted for investigation to determine the RH genotype in the USA population (inferred African American)
- 62/62 (including 2 heterozygous with RHef00107 and 1 with RHef00447) D positive random donors included for the development of a genotyping assay in the Dutch population
- 1 sample among SCD patients with Ab in the USA population, Illinois
- 235 alleles in 226 patients, SCD children systematically genotyped in an alloimmunization study in the USA population (Philadelphia)
- 15/27 (13 heterozygous with RHef00008) among 27 patients referred with different RH alloantibodies, who were found to have RHCE*ceMO allele African American
- 25/50 (19 heterozygous with RHef00008) among 50 donors, the majority referred because of ambiguous RH5 antigen typing, found to have RHCE*ceMO (44 with RHef00008, 6 with RHef00442) in the USA population
- 44/316 (18 heterozygous with RHef00447, 6 with RHef00058, 6 with RHef00313, 4 with RHef00317, 4 with RHef0020, 3 with RHef00067, 1 with RHef00018, 1 with RHef00046, 1 with RHef00009) among 316 (280 D positive and 36 D negative) donors genotyped African descent (FY:-1,-2) in the French population
- 96/127 (50 homo- or hemizygous, 46 in trans to a variant allele) The cohort was composed of 77 Tswa from Congo, 36 Biaka from Central African Republic, 14 Mbuti from Democratic Republic of the Congo. Pygmoid Central African
- 152/220 (64 hemi- or homozygous, 88 in trans to a variant allele) The cohort was composed of 164 Teke-Congolese (ethnic groups: 60 Akwa, 52 Mbochi, 52 Kuyu) from Congo, 19 Mandenka from Senegal, 25 Yoruba from Nigeria, 12 Bantu from Kenya. Nonpygmoid Central African
- 12/48 (2 heterozyguous with RHef00008) among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols African Brazilian
- 20 or more/67 among 405 random donor samples used to evaluate RHD zygosity tests (35 typed D negative, 303 typed D positive, 67 of the latter had discordant results with different methods and were sequenced) in the Tunisian population
- 29/35 had at least one RHef00442 SCD patients with unexplained RH antibodies, explored by NGS sequencing in the Brazilian population, Sao Paolo
- 200/200 (168 homozygous, 12 hemizygous, 19 heterozygous, 1 DD / D) D positive donors tested by MPLA Chinese, Southern Han
- 27 homozygote and 40 heterozygote samples among 278 samples selected for the development of nonspecific quantitative next-generation sequencing. (non-random samples, may have been reported in other studies)
Allele or phenotype frequency
- 0.538 estimated haplotype frequency Malian
- 0.607 allele frequency among 140 SCD patients African American (in the USA population)
- 0.639 allele frequency among 480 African American donors African American (in the USA population)
- 0.554 - 0.848 allele frequency from molecular typing of 46 random samples Fulani Malian
- 0.416 - 0.500 allele frequency from molecular typing of 101 random samples Dogon Malian
Structure mapping
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References
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- Noizat-Pirenne F et al. Relevance of RH variants in transfusion of sickle cell patients. Transfus Clin Biol, 2011. [Citation] [RHeference]
- Lomas-Francis C et al. DIII Type 7 is likely the original serologically defined DIIIb. Transfusion, 2012. [Citation] [RHeference]
- O'Suoji C et al. Alloimmunization in sickle cell anemia in the era of extended red cell typing. Pediatr Blood Cancer, 2013. [Citation] [RHeference]
- Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 2013. [Citation] [RHeference]
- Westhoff CM et al. RHCE*ceMO is frequently in cis to RHD*DAU0 and encodes a hr(S) -, hr(B) -, RH:-61 phenotype in black persons: clinical significance. Transfusion, 2013. [Citation] [RHeference]
- Granier T et al. A comprehensive survey of both RHD and RHCE allele frequencies in sub-Saharan Africa. Transfusion, 2013. [Citation] [RHeference]
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- Jakobsen MA et al. A case of high-titer anti-D hemolytic disease of the newborn in which late onset and mild course is associated with the D variant, RHD-CE(9)-D. Transfusion, 2014. [Citation] [RHeference]
- Reid ME et al. Genomic analyses of RH alleles to improve transfusion therapy in patients with sickle cell disease. Blood Cells Mol Dis, 2014. [Citation] [RHeference]
- Ba A et al. RH diversity in Mali: characterization of a new haplotype RHD*DIVa/RHCE*ceTI(D2). Transfusion, 2015. [Citation] [RHeference]
- Kacem N et al. Paternal RHD zygosity determination in Tunisians: evaluation of three molecular tests. Blood Transfus, 2015. [Citation] [RHeference]
- Sippert E et al. Variant RH alleles and Rh immunisation in patients with sickle cell disease. Blood Transfus, 2015. [Citation] [RHeference]
- Srivastava K et al. The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens. Transfusion, 2016. [Citation] [RHeference]
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- Thongbut J et al. RHD-specific microRNA for regulation of the DEL blood group: integration of computational and experimental approaches. Br J Biomed Sci, 2017. [Citation] [RHeference]
- Ouchari M et al. Serologic and molecular characterization of weak D type 29. Transfusion, 2017. [Citation] [RHeference]
- Ji YL et al. RHD genotype and zygosity analysis in the Chinese Southern Han D+, D- and D variant donors using the multiplex ligation-dependent probe amplification assay. Vox Sang, 2017. [Citation] [RHeference]
- Dezan MR et al. RHD and RHCE genotyping by next-generation sequencing is an effective strategy to identify molecular variants within sickle cell disease patients. Blood Cells Mol Dis, 2017. [Citation] [RHeference]
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- Stef M et al. RH genotyping by nonspecific quantitative next-generation sequencing. Transfusion, 2020. [Citation] [RHeference]
Last update: Jan. 14, 2021