IthaID: 1217



Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: Pathogenic / Likely Pathogenic
Common Name: CD 121 GAA>CAA [Glu>Gln] HGVS Name: HBB:c.364G>C
Hb Name: Hb D-Punjab Protein Info: β 121(GH4) Glu>Gln

Context nucleotide sequence:
TGTGCTGGCCCATCACTTTGGCAAA [G>C] AATTCACCCCACCAGTGCAGGCTGC (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKQFTPPVQAAYQKVVAGVANALAHKYH

Also known as: Hb D-Chicago, Hb D-North Carolina, Hb D-Portugal, Hb D-Los Angeles, Hb Oak Ridge

Comments: Association of Hb D-Punjab with another abnormal haemoglobin or β-thalassaemia allele leads to clinical symptoms ranging from mild to moderate disease, resembling either thalassemia minor or thalassemia intermedia. Association with the sickle mutation leads to a severe form of SS disease since Hb D-Punjab (β121Glu>Gln) enhances the polymerization of Hb S (with an effect trans to the Val-β6 in the contact site). No clinical or haematological alterations in heterozygosity or homozygosity. Double heterozygous HbS/Hb D-Punjab individuals from Badagas (an indigenous community of Nilgiris - India) also presented with heterozygous beta-globin BP1U distal promoter motif (AT)x (T)y (-530 cap site). The HbS gene associated with the Arab-Indian haplotype. The linkage of HbS with the (AT)9 (T)5 BP1U Arab-Indian haplotype reduces sickle gene expression and induces HbF, resulting in lesser sickle disease intensity. These genetics are also suggestive of a Harappan origin for the Badagas [PMID: 35221311].

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Phenotype

Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:N/A
Stability: N/A
Oxygen Affinity: N/A
Associated Phenotypes: N/A

Location

Chromosome: 11
Locus: NG_000007.3
Locus Location: 71938
Size: 1 bp
Located at: β
Specific Location: Exon 3

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: Missense codons (Protein Structure)
Ethnic Origin: Australian, Chinese, Dutch, English, Greek, Indian, Pakistani, Turkish, Yugoslavian
Molecular mechanism: N/A
Inheritance: Recessive
DNA Sequence Determined: Yes

HPLC

Disclaimer: The HPLC images are provided as an information resource only. Bio-Rad Laboratories, Inc and the ITHANET Portal disclaim responsibility and have no liability if this information is used for diagnostic or treatment purposes. D-10™ and VARIANT™ are registered trademarks of Bio-Rad Laboratories, Inc. and used with permission. Redistribution and use of the above material is allowed only with permission by Bio-Rad Laboratories, Inc. To access HPLC images and reports for different variants, use the IthaChrom tool.
ID Hb Variant Gene Instrument Method Area (%) Ret Time (min) Comments
535Hb D-PunjabβD-10Dual Kit Program37.93.74Compound heterozygote for HbS and Hb D-Punjab[PDF]
486Hb D-PunjabβD-10Dual Kit Program813.74[PDF]
477Hb D-PunjabβD-10Dual Kit Program70.83.7Double heterozygote Hb D-Punjab and beta-thalassaemia.[PDF]
421Hb D-PunjabβD-10Dual Kit Program293.81Heterozygous. Clinically normal in heterozygotes. Mild anemia in homozygotes. [PDF]
380Hb D-PunjabβD-10Dual Kit Program38.13.78heterozygote[PDF]
30Hb D-PunjabβD-10HbA1c Program41.51.63Heterozygous; Clinically normal in heterozygotes. Mild anemia in homozygotes. Causes a severe sickle cell disease when associated to HbS. [PDF]
22Hb D-PunjabβD-10HbA1c Program41.51.63Heterozygous; Clinically normal in heterozygotes. Mild anemia in homozygotes. Causes a severe sickle cell disease when associated to HbS. [PDF]
536Hb D-PunjabβVARIANTβ-thal Short Program40.74Compound heterozygote for HbS and Hb D-Punjab.[PDF]
478Hb D-PunjabβVARIANTβ-thal Short Program73.74.01Double heterozygote Hb D-Punjab and beta-thalassaemia. [PDF]
422Hb D-PunjabβVARIANTβ-thal Short Program283.99Heterozygous. Clinically normal in heterozygotes. Mild anemia in homozygotes.[PDF]
381Hb D-PunjabβVARIANTβ-thal Short Program37.44.08heterozygote[PDF]
215Hb D-PunjabβVARIANTβ-thal Short Program80.74.05Clinically normal in heterozygotes. Mild anemia in homozygotes. Causes a severe sickle cell disease when associated to HbS. [PDF]
540Hb D-PunjabβVARIANT IIDual Kit Program403.21Compound heterozygote for HbS and Hb D-Punjab[PDF]
538Hb D-PunjabβVARIANT IIβ-thal Short Program414.06Compound heterozygote for HbS and Hb D-Punjab.[PDF]
487Hb D-PunjabβVARIANT IIDual Kit Program84.83.212[PDF]
480Hb D-PunjabβVARIANT IIDual Kit Program75.43.191Double heterozygote Hb D-Punjab and beta-thalassaemia. [PDF]
479Hb D-PunjabβVARIANT IIβ-thal Short Program77.84.08Double heterozygote Hb D-Punjab and beta-thalassaemia. [PDF]
424Hb D-PunjabβVARIANT IIDual Kit Program30.63.276Heterozygous. Clinically normal in heterozygotes. Mild anemia in homozygotes.[PDF]
423Hb D-PunjabβVARIANT IIβ-thal Short Program28.84.08Heterozygous. Clinically normal in heterozygotes. Mild anemia in homozygotes.[PDF]
383Hb D-PunjabβVARIANT IIDual Kit Program38.53.233heterozygote[PDF]
382Hb D-PunjabβVARIANT IIβ-thal Short Program37.34.14heterozygote[PDF]
41Hb D-PunjabβVARIANT IIDual Kit Program - HbA1c42.21.83Heterozygous; Clinically normal in heterozygotes. Mild anemia in homozygotes. Causes a severe sickle cell disease when associated to HbS. [PDF]
31Hb D-PunjabβVARIANT IIHbA1c Program401.9Heterozygote; Heterozygous; Clinically normal in heterozygotes. Mild anemia in homozygotes. Causes a severe sickle cell disease when associated to HbS. [PDF]
23Hb D-PunjabβVARIANT IIHbA1c Program401.9 Heterozygous; Clinically normal in heterozygotes. Mild anemia in homozygotes. Causes a severe sickle cell disease when associated to HbS. [PDF]

In silico pathogenicity prediction

Sequence Viewer

Note: The NCBI Sequence Viewer is not installed on the ITHANET servers but it is embedded in this page from the NCBI. Therefore, IthaGenes has no responsibility over any temporary unavailability of the service. In such a case, please Refresh the page or retry at a later stage. Otherwise, use this external link.

Frequencies

Publications / Origin

  1. LEHMANN H, Three varieties of human haemoglobin D., Nature , 182(4639), 852-4, 1958 PubMed
  2. BOWMAN B, INGRAM VM, Abnormal human haemoglobins. VII. The comparison of normal human haemoglobin and haemoglobin D-Chicago., Biochim. Biophys. Acta , 53(0), 569-73, 1961 PubMed
  3. STOUT C, HOLLAND CK, BIRD RM, HEMOGLOBIN D IN AN OKLAHOMA FAMILY., Arch. Intern. Med. , 114(0), 296-300, 1964 PubMed
  4. Schneider RG, Ueda S, Alperin JB, Levin WC, Jones RT, Brimhall B, Hemoglobin D Los Angeles in two Caucasian families: hemoglobin SD disease and hemoglobin D thalassemia., Blood , 32(2), 250-9, 1968 PubMed
  5. Lehmann H, Carrell RW, Variations in the structure of human haemoglobin. With particular reference to the unstable haemoglobins., Br. Med. Bull. , 25(1), 14-23, 1969 PubMed
  6. Ozsoylu S, Homozygous hemoglobin D Punjab., Acta Haematol. , 43(6), 353-9, 1970 PubMed
  7. Imamura T, Riggs A, Identification of hemoglobin Oak ridge with hemoglobin D Punjab (Los Angeles)., Biochem. Genet. , 7(2), 127-30, 1972 PubMed
  8. Bunn HF, Altman AJ, Stangland K, Firshein SI, Forget B, Schmidt GJ, Jones RT, Hemoglobins Aida (alpha 64 Asp leads to Asn) and D-Los Angeles (beta 121 Glu leads to Gln) in an Asian-Indian family., Hemoglobin , 2(6), 531-40, 1978 PubMed
  9. Worthington S, Lehmann H, The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members., J. Med. Genet. , 22(5), 377-81, 1985 PubMed
  10. Husquinet H, Parent MT, Schoos-Barbette S, Dodinval-Versie J, Lambotte C, Galacteros F, Hemoglobin D-Los Angeles [beta 121(GH4)Glu----Gln] in the Province of Liège, Belgium., Hemoglobin , 10(6), 587-92, 1986 PubMed
  11. Li HJ, Liu DX, Li L, Liu ZG, Lo SL, Zhao J, Han XP, Yu WZ, A note about the incidence and origin of Hb D-Punjab in Xinjiang, People's Republic of China., Hemoglobin , 10(6), 667-71, 1986 PubMed
  12. Harano T, Harano K, Ueda S, Nakaya K, Hb D Los Angeles [beta 121 Glu----Gln] in Japan., Hemoglobin , 11(2), 177-80, 1987 PubMed
  13. Zeng YT, Huang SZ, Ren ZR, Li HJ, Identification of Hb D-Punjab gene: application of DNA amplification in the study of abnormal hemoglobins., Am. J. Hum. Genet. , 44(6), 886-9, 1989 PubMed
  14. Schnee J, Aulehla-Scholz C, Eigel A, Horst J, Hb D Los Angeles (D-Punjab) and Hb Presbyterian: analysis of the defect at the DNA level., Hum. Genet. , 84(4), 365-7, 1990 PubMed
  15. Fucharoen S, Changtrakun Y, Surapot S, Fucharoen G, Sanchaisuriya K, Molecular characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand., Hemoglobin, 26(3), 261-9, 2002 PubMed
  16. Gupta A, Saraf A, Dass J, Mehta M, Radhakrishnan N, Saxena R, Bhargava M, Compound heterozygous hemoglobin d-punjab/hemoglobin d-iran: a novel hemoglobinopathy., Indian J Hematol Blood Transfus , 30(0), 409-12, 2014 PubMed
  17. Archana R, Vidya C, Sumithra N, Jyothi M, Sanil R, Arab-Indian -530 ß-distal promoter haplotype and sickle/Hb D heterozygosis in Badagas of Nilgiris: is it suggestive of Harappan origin?, J Genet, 101(0), 0, 2022 PubMed
Created on 2010-06-16 16:13:17, Last reviewed on 2022-03-11 13:38:32 (Show full history)

Disclaimer: The information on this website is provided as an information resource only and must not to be used as a substitute for professional diagnosis and treatment. The ITHANET Portal and IthaGenes are not responsible or liable for any advice, course of treatment, diagnosis or any other information, services or products that an individual obtains through this website.